Ebook Paediatrics and child health: Part 1

Part 1 book “Paediatrics and child health” has contents: Emergency medicine, child protection, infectious diseases, cardiology, respiratory medicine, dermatology, ophthalmology, neurology, gastroenterology, renal diseases, blood diseases.

The Great Ormond Street Colour Handbook of Paediatrics and Child Health Stephan Strobel MD, PhD, MRCP(Hon), FRCP, FRCPCH Honorary Professor of Paediatrics and Clinical Immunology UCL Institute of Child Health, University College London, UK Director Peninsula Postgraduate Health Institute, Peninsula Medical School, Plymouth, UK Stephen D Marks MBChB, MSc, MRCP(UK), DCH, FRCPCH Consultant Paediatric Nephrologist Great Ormond Street Hospital for Children NHS Trust, London, UK Peter K Smith BMedSci, MBBS, FRACP, PhD Consultant Paediatric Allergist Bond University, Queensland, Australia Magdi H El Habbal MSc, MD, MRCPCH Consultant in Paediatrics and Cardiology Hull Royal Infirmary, UK Lewis Spitz MBChB, PhD, MD(Hon), FRCS(Edin), FRCS(Eng), FAAP(Hon), FRCPCH Nuffield Professor of Paediatric Surgery Great Ormond Street Hospital for Children NHS Trust, London, UK MANSON PUBLISHING CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2006 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S Government works Version Date: 20150311 International Standard Book Number-13: 978-1-84076-562-5 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and not necessarily reflect the views/opinions of the publishers The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately The authors and publishers have also attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint Except as permitted under U.S Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers For permission to photocopy or use material electronically from this work, please access www.copyright.com (http:// www.copyright.com/) or contact the Copyright Clearance Center, Inc (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400 CCC is a not-for-profit organization that provides licenses and registration for a variety of users For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com ACKNOWLEDGEMENTS The authors and editors would like to extend sincere thanks to the following people, who loaned clinical photographs and illustrations, advised, commented, and inspired In particular we are grateful to the children and families who have consented to the inclusion of their photographs in this handbook – which would not have been possible without their help and cooperation – and to the dedicated staff who cared for them Chapter 2, Child Protection: Professor Christine Hall, Great Ormond Street Hospital NHS Trust Chapter 3, Infectious Diseases: Dr Jane Crawley, John Radcliffe Hospital, Oxford Chapter 7, Ophthalmology: Professor Stephen A Vernon, University Hospital, Nottingham Chapter 8, Neurology: Professor Brian Neville, Professor Richard Robinson, Dr Helen Cross, Professor Robert Surtees, Dr Lucinda Carr, Dr Carlos de Sousa, Dr Sarah Benton, Dr Vijeya Ganesan, Dr John Wilson, Dr Edward Brett, Dr Colin Kennedy, and Dr Neil Thomas Chapter 9, Gastroenterology: Peter Milla (Professor of Paediatric Gastroenterology), Virpe Smith, Alan Ramsay, Peter Clayton (Professor of Metabolic Medicine) and the Histopathology Department of Great Ormond Street Hospital NHS Trust Chapter 10, Renal Diseases: Professor T M Barratt, Professor Michael Dillon, and Adrian Woolf Chapter 11, Blood Diseases: Dr Jon Pritchard (Hodgkin’s lymphoma) Chapter 13, Endocrinology: Professor M A Preece and Dr P C Hindmarsh Chapter 20, Otolaryngology: Tony Wright Chapter 22, Orthopaedics and fractures: Mr H Noordeen (Spinal problems) and Mr R Birch (Brachial plexus injuries) Contents CONTENTS Contributors Foreword 12 Preface 13 CHAPTER Emergency Medicine Introduction 15 Anaphylaxis 15 Upper airway obstruction 17 Asthma 20 Bronchiolitis 23 Cardiac emergencies 25 Cyanosis Cardiogenic shock Arrythmias Septic shock and multi-organ failure 28 The head-injured child 30 The child with multiple injuries 32 Burns 34 Diabetic ketoacidosis 35 Status epilepticus 37 Poisoning 40 Sedation in PICU 41 Methods of oxygen delivery 45 CHAPTER Child Protection Forms of child abuse 46 Physical abuse 48 Bite marks Bruises Burns and scalds Fractures Shaken baby syndrome Fabricated or induced illness Neglect 54 Sexual abuse 55 Management of child abuse 57 CHAPTER Infectious Diseases Bacteria 59 Diphtheria Tetanus Meningococcal infections Tuberculosis Tuberculous meningitis (TBM) Non-tuberculous mycobacterial infections (NTM) Staphylococcal toxic shock syndrome (TSS) Pyogenic liver abscess Viruses 69 HIV infection and AIDS Infectious mononucleosis Neonatal herpes simplex virus Varicella (chicken pox) Herpes zoster (shingles) Measles Protozoa/fungi/tropical diseases/miscellaneous 79 Congenital toxoplasmosis (CT) Cryptosporidiosis Cysticercosis (neurocysticercosis) Invasive aspergillosis Malaria Schistosomiasis (urinary) Kawasaki disease CHAPTER Respiratory Medicine Cystic fibrosis 88 Asthma and recurrent wheeze 90 Bronchiolitis 91 Pneumonia 92 Chronic aspiration 93 Pneumothorax 94 Empyema 95 Bronchiectasis 90 Pierre Robin anomalad 96 CHARGE association 97 Tracheobronchomalacia 98 Diaphragmatic hernia 99 Foreign body 100 Miliary pattern on chest imaging 101 Primary ciliary dyskinesia 102 Mycoplasma pneumoniae 103 Asphyxiating thoracic dystrophy 104 Pulmonary agenesis and aplasia 105 Congenital lobar emphysema (CLE) 105 Bronchogenic cyst 106 Congenital cystic adenomatoid malformation (CCAM) 107 Scimitar syndrome 108 Desquamative interstitial pneumonitis/fibrosing alveolitis 108 CHAPTER Cardiology Ventricular septal defect (VSD) 110 Atrial septal defect (ASD) 112 Coarctation of the aorta 113 Patent arterial duct (PAD) 114 Tetralogy of Fallot (ToF) 116 Pulmonary stenosis 118 Aortic stenosis 119 Cardiomyopathy 120 Supraventricular tachycardia (SVT) 121 Pericarditis and pericardial effusion 122 Heart block 123 Anomalous pulmonary venous drainage 124 Endocarditis 125 Tricuspid atresia 126 Transposition of great arteries 127 Corrected transposition of great arteries 128 Vascular ring 129 CHAPTER Dermatology Viral warts 131 Molluscum contagiosum 132 Atopic dermatitis (atopic eczema) 133 Scabies 134 Haemangioma 135 Orofacial herpes simplex 136 Pyogenic granuloma 137 Keloid 138 Pityriasis versicolor 139 Pityriasis rosacea 140 Vitiligo 140 Contents Psoriasis 141 Port wine stain 142 Urticaria pigmentosa 143 Eczema herpecticum 144 Erythema multiforme 145 Anogenital warts 147 Lichen striatus 148 Sebaceous naevus 148 Verrucous epidermal naevi 149 Langerhans cell histiocytosis (LCH) 151 Infantile acne vulgaris 152 Tuberous sclerosis 152 Juvenile dermatomyositis 153 Klippel-Trenaunay syndrome 154 Incontinentia pigmenti 155 Epidermolysis bullosa 156 Acrodermatitis enteropathica 158 CHAPTER Ophthalmology Anatomy of the eye 161 Visual development 163 Lids 164 Coloboma Symblepharon Blepharitis Molluscum contagiosum Capillary haemangioma Port wine stain Ptosis Lid retraction Preseptal cellulitis The watering eye Cornea 167 Developmental disorders Corneal dystrophies Keratitis Conjunctiva 174 Infection-related conjunctivitis Non infection-related conjunctivitis Conjunctival pigmentation Elevated conjunctival lesions Diffusely elevated conjunctival lesions Conjunctival telangiectasia Sclera 177 Pigmentation of the sclera Scleral inflammation Developmental anomalies of the globe 178 Iris 179 Congenital iris defects Aquired iris defects Changes in iris colour Heterochromia irides Pupil anomalies 182 Leukocoria Dyscoria Miosis Mydriasis Corectopia Anisocoria Lens anomalies 184 Aphakia Abnormal shape Dislocated lens Lens opacity Retinal anomalies 186 Haemorrhages Hard exudates Cotton wool spots Retinal neovascularization Retinal vasculitis Maculopathy Pale retinal lesions Retinal detachment Folds in the fundus The optic disc 191 Optic disc swelling Optic atrophy Small optic disc Large optic disc Large optic disc cup The orbit 194 Abnormalities of globe position Lacrimal gland enlargement Eye movement disorders 196 Ocular deviation in primary gaze Anomalous eye movements Abnormal head positions CHAPTER Neurology Neurological examination: cranial nerves 205 Myasthenia 207 Disorders of eye movement 208 Facial palsy 209 Lower cranial nerve abnormalities 211 Wilson’s disease 212 Sydenham’s chorea 212 Motor system 213 Segawa syndrome (Doparesponsive dystonia) 215 Ataxia 216 Ataxia-telangiectasia Friedreich’s ataxia Hypotonia in infancy 218 Hereditary motor and sensory neuropathy (CharcotMarie-Tooth disease) 220 Spinal muscular atrophy type (WerdnigHoffman disease) 221 Acute generalized weakness in a previously well child 221 Guillain-Barré syndrome 222 Dermatomyositis 223 Spinal cord disorders 224 Chronic and progressive weakness in the older child 225 Cerebral palsy 227 Spina bifida 229 Headaches 230 Migraine Psychogenic headaches Intracranial hypertension Hydrocephalus 232 Brain tumours 234 Common brain tumours in children 236 Macrocephaly 237 Psuedotumor cerebri (benign intracranial hypertension) 237 Learning difficulties 238 Epilepsy 240 Neurological and cognitive deterioration 243 Common conditions with neurological deterioration 244 Multiple sclerosis Adrenoleukodystrophy Krabbe’s (globoid cell) leukodystrophy Metachromic leukodystrophy Ceroid lipofuscinoses Tay Sach’s disease Leigh’s disease Coma and acute encephalopathies 246 Stroke 249 Contents CHAPTER Gastroenterology Clinical presentation 253 Acute gastroenteritis Failure to thrive Constipation Infantile colic Recurrent abdominal pain Toddler’s diarrhoea Chronic intractable diarrhoea Chronic intestinal failure Gastrointestinal diagnoses 261 Fabricated and induced illness Coeliac disease Food-sensitive enteropathy Autoimmune enteropathy Eosinophilic gastroenteropathy Classic inflammatory bowel disease Ulcerative colitis Crohn’s disease Allergic colitis Lymphangiectasia Ulcers Polyps Infections and infestations 272 Helicobacter pylori Campylobacter jejuni Clostridium difficile Salmonella Pathogenic Escherichia coli Giardia lamblia Yersinia enterocolitica Cryptosporidium Ascaris lumbricoides (roundworm) Enterobius vermicularis (threadworm) Feeding problems 277 Gastro-oesophageal reflux 278 Intestinal pseudoobstruction 279 Short bowel syndrome 279 Congenital and inherited disorders 281 Congenital chloride diarrhoea Glucose galactose malabsorption Sucrose-isomaltase deficiency Lactose malabsorption Cystic fibrosis Pancreatic disease 284 Shwachman-Diamond syndrome Acute pancreatitis Chronic/hereditary pancreatitis Liver disease 286 Sclerosing cholangitis Chronic hepatitis Acute hepatitis Alagille syndrome Mineral deficiencies 288 Zinc deficiency Iron deficiency Copper deficiency Copper excess: Wilson’s disease Selenium deficiency Vitamin deficiencies 291 Scurvy, vitamin C/ascorbic acid deficiency Beriberi, vitamin B1, thiamin deficiency Pellagra/niacin deficiency Riboflavin/vitamin B2 deficiency Cyanocobalamin/vitamin B12 deficiency Vitamin K/napthaquinone deficiency Retinol/vitamin A deficiency Tocopherol/vitamin E deficiency Vitamin D deficiency CHAPTER 10 Renal Diseases Haemolytic uraemic syndrome (HUS) 297 Nephrotic syndrome 299 Polycystic kidney diseases 301 Vesico-ureteric reflux and its nephropathy 302 Henoch-Schönlein purpura 304 Renal agenesis and dysplasia 305 Renal Fanconi syndrome 306 Childhood hypertension due to reno-vascular disease 307 Renal bone disease in children with chronic renal failure 308 Acute renal failure 310 CHAPTER 11 Blood Diseases Hodgkin’s lymphoma 313 B-cell non-Hodgkin’s lymphoma 314 T-cell non-Hodgkin’s lymphoma (NHL)/leukaemia 315 Monocytic and myelomonocytic leukaemia 316 Extramedullary acute lymphoblastic leukaemia 317 Juvenile myelomonocytic leukaemia 318 Eosinophilic myeloproliferative disorder with chromosomal 5;12 translocation (t5;12) 319 Severe haemophilia A and B (classic haemophilia and Christmas disease) 320 Kasabach-Merritt syndrome 321 Von Willebrand’s disease (vWD) 321 Thrombocytopenia with absent radius (TAR) 322 Bernard-Soulier syndrome 323 Transcobalamin II deficiency 324 Fanconi anaemia 324 Dyskeratosis congenita 325 Congenital erythropoietic porphyria (CEP) 326 Idiopathic pulmonary haemosiderosis 327 Beta thalassaemia major 328 Pyruvate kinase deficiency 330 Sickle cell disease 330 Hereditary elliptocytosis 332 Iron deficiency anaemia 332 Sideroblastic anaemia 333 Glucose-6-phosphate deficiency 333 Leishmaniasis 334 Gaucher disease 334 Osteopetrosis 335 CHAPTER 12 Solid Tumours and Histiocytosis Introduction 337 Wilms’ tumour and other renal tumours 338 Liver tumours 341 Histiocytosis 342 Langerhans cell histiocytosis (LCH) Haemophagocytic lymphohistiocytosis (HLH) Rhabdomyosarcoma, other soft tissue sarcomas and fibromatosis 348 Neuroblastoma 352 Retinoblastoma 354 Contents Ewing’s sarcoma and peripheral primitive neuroectodermal tumour (pPNET) 355 Osteosarcoma 356 Extracranial malignant germ cell tumours 357 Tumours of the central nervous system 358 Ependymoma Medulloblastoma/pNET High-grade supratentorial glioma Brain stem glioma Low grade astrocytoma Rare tumours and rare manifestations of common tumours 361 Carcinomas 361 Thyroid carcinoma Nasopharyngeal carcinoma (NPC) Adrenocortical carcinoma (ACC) Salivary gland tumours Renal cell carcinoma (RCC) Skin cancers 364 Late effects of cancer treatment 365 CHAPTER 13 Endocrinology Ambiguous genitalia 367 The short child 368 Turner syndrome 370 Low birth weight syndrome 371 Prader-Willi syndrome 372 Skeletal dysplasias 373 Growth hormone deficiency/insufficiency 374 Laron-type dwarfism 376 Tall stature 377 Marfan syndrome 378 Pituitary gigantism 379 Early puberty 380 Premature thelarche/thelarche variant or ‘benign’ precocious puberty 381 Gonadotrophin-dependent (central) precocious puberty 382 McCune-Albright syndrome 383 Polycystic ovarian disease 384 Late puberty 385 Klinefelter syndrome 386 Congenital hypothyroidism 387 Acquired hypothyroidism 388 Primary adrenal insufficiency 389 Cushing syndrome 390 Congenital adrenal hyperplasia 392 Rickets 393 Graves’ disease 394 Hypoparathyroidism/pseudohypoparathyroidism 395 Williams syndrome 397 Hyperinsulinism 398 Insulin resistance syndromes 399 Diabetes mellitus 400 Adrenoleukodystrophy 406 Gaucher disease 407 Hurler’s disease 408 Urea cycle disorders 409 Galactosaemia 410 Fatty acid oxidation defects 411 Tyrosinaemia 412 Glycogen storage disease type 413 Peroxisomal biogenesis disorders 414 Leigh syndrome 415 Menke’s disease 416 Wilson’s disease 417 Phenylketonuria 418 Biotin disorders 419 Alpha-1-antitypsin deficiency (AT) 420 De Lange syndrome 428 Angelman syndrome 429 Frontonasal dysplasia 430 VATER association 430 Goldenhar syndrome 431 Bardet-Biedl syndrome 432 CHARGE association 432 Marfan syndrome 433 Velocardiofacial syndrome 433 Tuberous sclerosis 434 Neurofibromatosis type 435 Moebius syndrome 436 Stickler syndrome 436 Russell-Silver syndrome 437 Achondroplasia 437 Hypochondroplasia 438 Osteogenesis imperfecta 438 Ehlers-Danlos syndrome 439 Beckwith-Wiedemann syndrome 440 Sotos syndrome 440 Robinow syndrome 441 EEC syndrome 441 Cockayne syndrome 442 Apert syndrome 442 Pfeiffer syndrome 443 Crouzon syndrome 444 Holoprosencephaly 444 Coffin-Lowry syndrome 445 Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) 445 Meckel-Gruber syndrome 446 Greig syndrome 446 Holt-Oram syndrome 447 Roberts syndrome 447 Microcephaly 448 Fanconi anaemia 448 CHAPTER 15 Genetics CHAPTER 16 Immunology Down syndrome (trisomy 21) 421 Edwards syndrome (trisomy 18) 422 Patau syndrome (trisomy 13) 422 Wolf-Hirschhorn syndrome (4p–) 423 Cri-du-chat syndrome (5p–) 423 Turner syndrome (XO) 424 Noonan syndrome 424 Chromosome mosaicism 425 Fragile X syndrome 426 Williams syndrome 426 Rubinstein-Taybi syndrome 427 Common variable immunodeficiency (CVID) 449 Hypogammaglobulinaemia with hyper-IgM (CD40 ligand deficiency) 450 Wiskott-Aldrich syndrome 451 X-linked agammaglobulinemia (Bruton’s disease) 452 Chronic mucocutaneous candidiasis (CMC) 453 Ataxia-telangiectasia 454 X-linked lymphoproliferative disease (XLP, Duncan’s syndrome) 455 Chediak-Higashi syndrome 456 Leukocyte adhesion defects 457 Type diabetes Type diabetes Maturity Onset Diabetes of the Young (MODY) CHAPTER 14 Metabolic Diseases Contents Di George syndrome 459 Chronic granulomatous disease (CGD) 460 Hyper-IgE syndrome 461 Severe combined immunodeficiency (SCID) 462 Omenn syndrome (SCID variant) 463 Adenosine deaminase (ADA) deficiency (SCID variant) 464 MHC (major histocompatibility complex) class II deficiency 465 CHAPTER 17 Rheumatology Juvenile idiopathic arthritis (JIA) 467 Systemic onset JIA Polyarticular onset: rheumatoid factor negative JIA Polyarticular onset: rheumatoid factor positive JIA Oligoarticular arthritis Enthesitis-related arthritis 470 Psoriatic arthritis 471 Arthritis associated with other chronic diseases 471 Scleroderma 472 Systemic sclerosis Localized scleroderma Dermatomyositis 473 Vasculitides 474 Kawasaki disease Polyarteritis nodosa (PAN) Henoch-Schönlein purpura 475 Mixed connective tissue disease (MCTD) 475 Systemic lupus erythematosus (SLE) 476 Overlap connective tissue disease (CTD) 476 Chronic infantile neurological cutaneous and articular syndrome (CINCA) 477 Chronic recurrent multifocal osteomyelitis (CRMO) 478 Periodic fever syndromes 478 Familial Mediterranean fever Other genetic periodic fevers Chronic pain syndrome 479 Fibromyalgia 479 Reflex sympathetic dystrophy (algodystrophy) 479 Benign joint hypermobility syndrome 480 CHAPTER 18 Speech and Language Therapy Introduction 481 Developmental difficulties: speech 482 Developmental difficulties: language 483 Alternative and augmentative communication (AAC) 484 Acquired neurological speech and language disorders 484 Acquired childhood aphasia Aquired childhood dysarthria Acquired childhood articulatory dyspraxia Stammering/stuttering dysfluency 486 Voice disorders/dysphonia 487 Tracheostomy 488 Resonance/airflow disorders 489 Dysphagia 490 Craniofacial conditions 491 Cleft lip/palate 492 CHAPTER 19 Neonatal and General Paediatric Surgery Oesophageal atresia 496 Congenital diaphragmatic hernia 497 Neonatal intestinal obstruction 499 Meconium ileus Duodenal atresia Intestinal atresia Anorectal anomalies Hirschsprung’s disease Malrotation Duplications of the alimentary tract Necrotizing enterocolitis (NEC) Exomphalos Gastroschisis Umbilical hernia Umbilical anomalies 510 Gastrointestinal haemorrhage 511 Meckel’s diverticulum 512 Intussusception 513 Sacrococcygeal teratoma 514 Appendicitis 515 Neck lesions 516 Cystic hygroma Branchial sinus/cyst Preauricular sinus Dermoid cysts Thyroglossal cysts/fistulae Inguinal hernia 518 Hydrocoele 519 Undescended testis 520 Torsion of the testis 520 Phimosis 521 Biliary atresia 522 Choledochal cyst 522 Vascular malformations 525 Haemangioma Congenital vascular malformations Klippel-Trenaunay syndrome Lymphoedema 525 Spina bifida 526 CHAPTER 20 Otorhinolaryngology Otitis media with effusion (OME, ‘glue ear’) 529 Acute otitis media (AOM) 531 Cholesteatoma 532 Chronic suppurative otitis media (CSOM) 533 Otitis externa 534 Aural polyps 534 Aural foreign bodies 535 Congenital anomalies of the ear 535 Pre-auricular sinus and abscess External ear Middle ear anomalies Inner ear anomalies Nasal polyps 536 Rhinosinusitis 537 Nasal mass 538 Nasal glioma Postnasal angiofibroma Nasal foreign bodies 539 Choanal atresia 539 Tonsillitis (acute, chronic and recurrent) 540 Peritonsillar abscess (quinsy) 541 Retropharyngeal abscess 541 Obstructive sleep apnoea (OSA) 541 322 Blood diseases TREATMENT The majority are treated with DDAVP, which releases endogenous vWF from endothelium and megakaryocytes Severe (type III) patients are treated with a combination of von Willebrand factor protein and factor VIII The prognosis is excellent and the same infective risks of blood products apply to patients with von Willebrand’s disease as with other bleeding disorders THROMBOCYTOPENIA WITH ABSENT RADIUS (TAR) PRESENTATION The diagnosis is usually made at birth because of the characteristic physical appearance combined with thrombocytopenia The pathognomonic physical finding is bilateral absence of the radii with thumbs present (11.26) which can distinguish TAR from Fanconi anaemia (see page 324) in which thumbs may be absent and the radii are present (11.27) DIAGNOSIS Clinical observation and blood count showing severe thrombocytopenia There may be other associated findings, including hand anomalies and abnormalities of the shoulder, neck and lower limbs Skin haemangiomas also occasionally occur Females are more often affected than boys, as opposed to Fanconi anaemia where there is a male predominance The diagnosis must be distinguished from ITP and from megakaryocytic thrombocytopenia (other than ITP) because this latter condition has a propensity to the development of marrow aplasia and myelodysplasia TREATMENT Most patients bleed in infancy and then improve after the first year In the past, mortality was approximately 25%, the majority of deaths occurring in the first year Platelet transfusions should be used during bleeding episodes or operations, including those to correct the deformities Occasional transient responses to splenectomy have occurred and tranexamic acid may be useful for mucosal bleeding but must not be used when haematuria (macroscopic or microscopic) occurs There are also anecdotal reports of responses to immunoglobulin therapy 11.26 Thrombocytopenia with absent radius (TAR) X-ray showing that radii are absent PROGNOSIS If the patient survives the first year the prognosis is excellent 11.27 X-ray showing that thumbs are absent in Fanconi anaemia Bernard-Soulier syndrome BERNARD–SOULIER SYNDROME PRESENTATION Usually with epistaxis and mucocutaneous bleeding within the first year of life Bleeding into joints or muscles does not occur DIAGNOSIS Like the other thrombocytopenias of infancy, the predominant clinical feature is bleeding (see above) The gene has been mapped to the short arm of chromosome 17 (in the region 17pter-17p12) Platelets from these patients have a reduced number of platelet membrane glycoproteins Bernard-Soulier syndrome is caused by mutations in GPIb-α, GPIb-β or GPIX These proteins act as receptors for von Willebrand's factor and, when absent, platelets fail to adhere to the subendothelial matrix The proteins are usually quantified on the platelet surface via fluorescence-activated cell-sorting (FACS) analysis, using specific monoclonal antibodies The other main diagnostic pointer is the presence of a reduced number of platelets (40–80 × 109/l) which are usually large in size Differential diagnosis for thrombocytopenia would include Wiskott-Aldrich syndrome which, unlike the Bernard-Soulier defect (11.28, 11.29), is associated with very small platelets, TAR, amegakaryocytic thrombocytopenia, and artefactual thrombocytopenia (11.30) This artefact is usually caused by an EDTA-induced antibody and the effect can be abrogated by the use of an alternative anticoagulant such as citric acid TREATMENT The only available therapy is transfusion with platelet concentrates Affected patients usually receive this therapy only for persistent and significant haemorrhage, since the transfused patient may develop antibodies against the missing blood protein, making them permanently refractory to therapy Tranexamic acid may be used for mucosal bleeds but not for patients with haematuria 11.28 Bernard-Soulier syndrome Blood film 11.29 Bernard-Soulier syndrome Blood film 323 11.30 Artefactual thrombocytopenia Blood diseases 324 TRANSCOBALAMIN II DEFICIENCY PRESENTATION Patients usually present at three to five weeks of age with failure to thrive, weakness, hypotonia (11.31) and diarrhoea, in addition to pallor due to severe progressive anaemia Some patients present with pancytopenia Transcobalamin II is the principal transporter for B12 entry into cells, and the serum vitamin B12 level is normal because it is transported in the plasma by transcobalamin I The bone marrow is severely megaloblastic (11.32) and the blood film shows macrocytosis and other features of megaloblastic anaemia Homocystinuria and methylmalonic aciduria have also been found in some cases There is some evidence of autosomal inheritance associated with an abnormality in chromosome 22 DIAGNOSIS Absence of the protein capable of binding radiolabelled cobalamin and migrating with TCII, on chromotography or gel electrophoresis TREATMENT Vitamin B12 must be kept high with systemic injections of hydroxycobalamin (IM) approximately 500–1,000 mg twice-weekly The prognosis for neurological abnormalities depends upon whether or not treatment is instituted early and patients must be closely monitored for any deterioration in neurological status at which stage the vitamin B12 injections should be increased in dosage FANCONI ANAEMIA PRESENTATION Usually at around six years of age, with hyperand hypo-pigmentation (11.33), short stature, abnormalities of the thumbs and radii (11.34), hypogonadism, microcephaly and microphthalmia (11.35) Renal abnormalities are also common and, being a bone marrow failure syndrome, the patients may present with bleeding and infection 11.31 Transcobalamin II deficiency DIAGNOSIS Laboratory: investigations include blood count showing a single cytopenia (usually thrombocytopenia but pancytopenia may also be the presenting haematological feature) Confirmation is by increased spontaneous chromosomal breakage induced with clastogenic agents (e.g diepoxybutane [DEB]) TREATMENT Chromosome fragility syndromes are associated with a high risk of developing acute leukaemia The progressive bone marrow failure may be temporarily managed with oxymetholone but the only curative procedure is bone marrow transplantation Gene therapy may be a future possible treatment 11.32 Transcobalamin II deficiency Blood film showing megaloblastic bone marrow Dyskeratosis congenita 325 DYSKERATOSIS CONGENITA PRESENTATION This is a rare form of ectodermal dysplasia Skin and nail changes are usually seen in the first decade of life, with leukoplakia in the second All features become more extreme with age There is a reticulated type of pigmentation of the face, neck and shoulders, dystrophic nails (11.36) and mucous membrane leukoplakia Aplastic anaemia occurs in 50% of patients, usually during the second decade and cancer in 10% by the 3rd and 4th decade 11.33 Fanconi anaemia Facial appearance DIAGNOSIS Most patients present with thrombocytopenia or anaemia and then develop pancytopenia Macrocytosis and elevated haemoglobin F are common Chromosomal breakage studies are usually normal The Xq28 restriction fragment length polymorphism (RFLP) might be used for prenatal diagnosis There is an association with failure of cerebellar development (the HH syndrome) TREATMENT Some patients respond to androgens, but supportive care has been the only effective holding measure, with bone marrow transplantation the only possible chance of cure 11.34 Fanconi anaemia Thumb abnormalities 11.35 Fanconi anaemia Microphthalmia 11.36 Dyskeratosis congenita Dystrophic nails 326 Blood diseases CONGENITAL ERYTHROPOIETIC PORPHYRIA (CEP) 11.37 Congenital erythropoietic porphyria Skin erosions as a result of photosensitivity 11.38 Congenital erythropoietic porphyria Phototoxic damage to hands PRESENTATION A rare form of porphyria; this diagnosis may be suspected when pink to dark brown stains are noted in the nappy (due to large amounts of porphyrins in the urine) At an early stage, cutaneous photosensitivity is obvious and is exacerbated by any exposure to sunlight Initial subepidermal bullous lesions progress to crusted erosions (11.37–11.40) which heal with scarring and (usually) increased pigmentation Hypertrichosis and alopecia are frequent and erythrodontia (red fluorescence under ultraviolet light) (11.41) are virtually pathognomonic of the disease The patients may also display symptoms of haemolytic anaemia with splenomegaly and gall stones DIAGNOSIS Urinary porphyrins are greatly elevated due to decreased activity of uroporphyrinogen III cosynthase activity The bone marrow shows porphyrin fluorescence in the red cells when exposed to UV light The definitive diagnosis is a demonstration of a deficiency of uroporphyrinogen III cosynthase activity TREATMENT Avoid sunlight and trauma to the skin Topical sun screens may be of help, as may oral treatment with beta-carotine The haemolysis may be mild or more severe and should be treated with blood transfusion and sometimes splenectomy Bone marrow transplantation may be curative 11.39 Congenital erythropoietic porphyria 11.40 Congenital erythropoietic porphyria Blistering on hands 11.41 Congenital erythropoietic porphyria Discolouration of the teeth Idiopathic pulmonary haemosiderosis IDIOPATHIC PULMONARY HAEMOSIDEROSIS PRESENTATION The disease may present at any time in childhood and as early as the neonatal period It is characterized by recurrent intrapulmonary haemorrhage The patient may have haemoptysis and dyspnoea, with a subsequent iron deficiency anaemia The sputum is characteristically ‘rusty’ There may be associated fever, tachycardia, tachypnoea, leukocytosis and occasionally abdominal pain DIAGNOSIS The direct Coombs’ test may be positive The blood count shows microcytic hypochromic anaemia Chest x-rays vary from minimal infiltrates (11.42) to massive ones with parenchymal involvement, atelectasis, emphysema and hilar adenopathy (11.43) Siderophages are found in the gastric aspirate and they stain positive with Prussian blue Lung biopsy shows alveolar epithelial hyperplasia, degeneration with excessive shedding of cells, large numbers of siderocytes, varying amounts of interstitial fibrosis and mast cell accumulation, elastic fibre degeneration and sclerotic vascular changes 11.42 Idiopathic pulmonary haemosiderosis Chest x-ray showing minimum infiltrates TREATMENT Steroid therapy sometimes produces a remission, and there have been alleged responses to withdrawal of milk from the diet in a few cases 11.43 Idiopathic pulmonary haemosiderosis Chest x-ray showing hilar adenopathy 327 Blood diseases 328 BETA THALASSAEMIA MAJOR PRESENTATION Severe anaemia, very often exacerbated by folic acid deficiency, which may lead to pancytopenia At a later stage, patients who are severely affected develop overgrowth of the bones due to marrow expansion A good example is shown in 11.44, where the patient on the right was not transfusion-dependent and developed marrow overgrowth because of failure of marrow suppression The patient on the left also had beta thalassaemia major and developed hyperpigmentation of the skin due to iron overload from blood transfusion, but the marrow was adequately suppressed and thus maxillary and other bony overgrowth did not occur If patients are not transfused they develop massive hepatosplenomegaly and wasting (11.45) The x-rays opposite (11.46–11.48) show expansion of the marrow cavity leading to a ‘hair on end’ appearance in the skull and expansion and thinning of the bones elsewhere DIAGNOSIS The diagnosis depends on showing the presence of beta thalassaemia trait in the parents, along with either a raised haemoglobin A2 level or the existence of a coexisting haemoglobinopathy such as haemoglobin E The blood film (11.49) shows hypochromia and microcytosis, and haemoglobin electrophoresis of the patient shows mainly HbF with some haemoglobin A2 Confirmation is either with demonstration of the lack of globin chain synthesis or by molecular methods 11.44 Beta thalassaemia major The patient on the right has developed marrow overgrowth in the facial bones 11.45 Beta thalassaemia major Hepatosplenomegaly Beta thalassaemia major TREATMENT The only curative treatment at present is with bone marrow transplantation, the outcome of which is excellent if a matched sibling donor is available and the transplant is carried out in the first few years of life Otherwise, unrelated donor transplant could be considered, but the standard treatment at present is with regular blood transfusion, splenectomy following vaccination against Pneumococcus, Haemophilus and Meningococcus C, and supplementation with vitamin C, folic acid and penicillin prophylaxis (post splenectomy) At a later stage, iron overload becomes a major problem and regular chelation with at least five times per week subcutaneous desferrioxamine is required If iron overload ensues, multiple endocrinopathies including diabetes mellitus occur, with eventual cardiac failure 11.48 Beta thalassaemia major 11.46 Beta thalassaemia major 11.47 Beta thalassaemia major 11.49 Beta thalassaemia major Blood film 329 Blood diseases 330 PYRUVATE KINASE DEFICIENCY PRESENTATION The child has a congenital non-spherocytic haemolytic anaemia which may present with hyperbilirubinaemia Autosomal recessive inheritance is usually observed Splenomegaly is usually present Found predominantly in people of Northern European descent Erythroblastopenic crisis from parvovirus B19 infection is not uncommon DIAGNOSIS Blood film shows macrocytosis and occasional shrunken, spiculated erythrocytes (Echinocytes, 11.50) Direct measurement of the pyruvate kinase (PK) enzyme shows a reduced level and there should be a concomitant high level of 2,3-Diphosphoglycerate (2,3DPG) Red cell intermediates of metabolism may be helpful in those patients with a marginally low PK level, or with a dysfunctional enzyme or very high reticulocyte count A severe anaemia is usually present and this may be well tolerated due to a shift to the right of the oxygen dissociation curve, secondary to a raised 2,3DPG Hyperbilirubinaemia, low haptoglobins and raised reticulocyte levels are usually found The enzyme level may be spuriously elevated due to relatively high PK levels in the reticulocytes and the assay must be corrected for this TREATMENT The patients often tolerate a low haemoglobin of around 6g/dL very well because of the compensatory raised 2,3DPG level Eventually the patients require splenectomy and, contrary to some previous reports, the results are usually very good Folic acid supplementation is indicated SICKLE CELL DISEASE PRESENTATION These patients are nowadays picked up on haemoglobinopathy screening and by neonatal screening programmes The most common problem is a painful crisis, which may involve the hand and produce dactylitis (11.51), possibly leading to osteomyelitis (11.52, 11.53,) Sickle chest syndrome involves sequestration in the lungs (11.54) The patient may also present at an early age with an aplastic crisis in which red cell production is impaired by parvovirus B19 infection Also, an early and life threatening problem is sickle cell sequestration in the spleen and a rapid drop in haemoglobin due to pooling of blood DIAGNOSIS Diagnosis is by haemoglobin electrophoresis and family studies The electrophoretic pattern will show haemoglobin S In haemoglobin SC 11.51 Sickle cell disease Dactylitis 11.50 Pyruvate kinase deficiency Blood film showing macrocytosis and spiculated erythrocytes Sickle cell disease disease, there is an extra band on electrophoresis and in haemoglobin S beta thalassaemia one parent will have sickle cell trait and one parent will have beta thalassaemia trait Blood films shows the presence of sickle and target cells; the latter being more common in haemoglobin SC disease (11.55, 11.56) MANAGEMENT Early diagnosis is essential and may be picked up on neonatal screening Early institution of penicillin prophylaxis is essential and treatment of painful crisis is with plentiful fluids and patient-controlled analgesia For serious complications, such as chest syndrome and stroke, exchange transfusion is essential at a very early stage Patients with recurrent severe problems may be considered for bone marrow transplantation 11.54 Sickle cell disease Pulmonary sequestration 11.52 Sickle cell disease Periosteal elevation due to osteomyelitis 11.55 Sickle cell disease Blood film showing sickled cells and target cells 11.53 Sickle cell disease Osteomyelitis 11.56 Sickle cell disease Blood film showing sickled cells and target cells 331 Blood diseases 332 HEREDITARY ELLIPTOCYTOSIS PRESENTATION Often asymptomatic When there is recessive inheritance, the patient may present with a severe haemolytic anaemia if homozygous DIAGNOSIS This disorder is associated with classic blood film appearances (11.57) of many ovalocytes In patients with the severe form of hereditary homozygous elliptocytosis, red cell fragmentation is often present TREATMENT Most patients with hereditary elliptocytosis need no therapy at all Patients with the severe homozygous form may require splenectomy IRON DEFICIENCY ANAEMIA PRESENTATION May often be asymptomatic Can be associated with pica and is often associated with a poor diet with regard to iron content In severe cases, cardiac failure, failure to thrive or developmental delay may be the presenting clinical features The patient may look very pale but the ability to pick this up clinically is limited (11.58) DIAGNOSIS This is a controversial area because none of the tests are very satisfactory A low haemoglobin with low mean red cell volume and low red cell count in the blood, associated with a low ferritin, low iron and raised total iron binding capacity (TIBC), is the classical presentation Serum transferrin receptor level estimation may add additional information TREATMENT The patient must be treated with iron until the haemoglobin rises to a normal level and then for a further three months to replete the iron stores This must be associated with extensive dietary advice otherwise the problem will recur If the problem is a recurrent one then causes of blood loss such as intestinal parasites, or a malabsorptive disorder such as coeliac disease should be considered See also ‘Gastroenterology’ chapter 11.57 Hereditary elliptocytosis Blood film showing ovalocytes 11.58 Iron deficiency anaemia Facial appearance Glucose-6-phosphate deficiency SIDEROBLASTIC ANAEMIA PRESENTATION The sideroblastic anaemias (SA) are a heterogeneous group of anaemias and thus can present with mild to severe anaemia at any stage during childhood Characteristically they have a hypochromic/microcytic or normochromic/microcytic anaemia, refractory to iron therapy, and hepatosplenomegaly is not an uncommon finding at presentation Of the congenital types, X-linked inheritance is the commonest When the anaemia is macrocytic and refractory to pyridoxine within the first six months of life, Pearson’s syndrome should be considered This is a multi-system disorder, characterized by deletion rearrangements of mitochondrial DNA (mt DNA), that leads to defects in respiratory chain function Vacuolization of marrow precursors and the presence of sideroblasts, along with exocrine pancreatic insufficiency, suggest the diagnosis Acquired sideroblastic anaemia has been associated with drugs, autoimmune disease, neoplasia and endocrinopathies DIAGNOSIS Bone marrow aspirate with iron staining showing ringed sideroblasts (11.59), plus quantitative measurement of haemoglobin A2 and HbF, are necessary as a screening test for this disorder Southern blotting analysis of mtDNA is required to make the diagnosis of Pearson’s syndrome TREATMENT Transfusion and iron chelation is the mainstay of treatment for SA A trial of pyridoxine therapy is worthwhile Allogeneic bone marrow transplantation has been used successfully in severe forms Treatment of the underlying cause in the acquired forms usually alleviates the SA 11.59 Sideroblastic anaemia Bone marrow aspirate showing ringed sideroblasts 333 GLUCOSE-6-PHOSPHATE DEFICIENCY PRESENTATION Most patients are asymptomatic and are picked up on screening prior to surgery or drug therapy such as anti-malarial treatment Some patients present with intravascular haemolysis and haemoglobinuria (‘Coca-Cola urine’) This haemolysis is usually precipitated by the use of a drug or the ingestion of broad beans (favism) Occasional patients can present with chronic haemolysis and the consequent production of gallstones DIAGNOSIS The diagnosis is based on a screening test for glucose phosphate dehydrogenase (G6PD) Patients with massive intravascular haemolysis often have bucket-handle forms of the red blood cells (11.60) This is due to retraction of haemoglobin away from the red cell membrane TREATMENT Specific treatment is not required except in the vary rare case of chronic haemolysis, which may respond to splenectomy The majority of patients should be issued with a list of drugs and foods to be avoided Drugs and chemicals that may cause haemolysis in G6PD deficiency • • • • • • Acetanilide Chloramphenicol Daunorubicin Dapsone Methylene blue Nalidixic acid • • • • • Nitrofurantoin Pamaquine Pentaquine Phenylhydrazine Sulphonamides 11.60 G6PD deficiency Blood film showing ‘bucket-handle’ forms of red blood cells Blood diseases 334 LEISHMANIASIS GAUCHER DISEASE PRESENTATION Visceral leishmaniasis (Kala-azar) is a chronic debilitating infection that is endemic in the Mediterranean basin, East Africa, Northern East India, China and South America The causative organism is Leishmania donovanii (LD), which is transmitted by the sandfly (Phlebotomus) The type seen in the Mediterranean usually affects younger children (Leishmania infantum) The protozoan infects the macrophage compartment of the reticuloendothelial system resulting in massive splenomegaly, hepatomegaly, pancytopenia and swinging fevers See also ‘Metabolic Diseases’ chapter DIAGNOSIS Usually made following analysis of the bone marrow, in which macrophages are glutted with LD bodies (amastigotes, 11.61) Splenic aspiration and serological markers are alternative diagnostic modalities PRESENTATION This is the commonest type of inherited lipidosis There is great inter-individual variation in the degree of clinical involvement Most patients have hepatosplenomegaly (11.62), Gaucher cells in the bone marrow and accumulation of glucosylceramide The presentation depends on the disease type: • Type Chronic, non-neuronopathic adult-type Gaucher disease • Type Acute, neuronopathic (infantile type) Gaucher disease • Type Sub-acute, neuronopathic-type juvenile Gaucher disease Diagnosis is thus based on the measurement of the enzyme and detection of Gaucher cells in the marrow aspirate (11.63) and trephine (11.64) TREATMENT Worldwide, antimonials are the most frequently used agents in kala-azar These are not without serious side-effects (kidney/liver/heart) and, more recently, amphotericin B and the more effective liposomal amphotericin B have been used with impressive results 11.62 Gaucher disease Hepatosplenomegaly 11.61 Leishmaniasis Amastigotes in the bone marrow 11.63 Gaucher cells in marrow aspirate Osteopetrosis TREATMENT Patients with type 1, adult, chronic, neuronopathic Gaucher disease may be treated with ceridase, which is a commercial form of the missing enzyme, or with bone marrow transplantation The patients with the acute, neuronopathic, type 2, infantile Gaucher disease have an early onset and fatal outcome and thus prenatal diagnosis is the most feasible alternative management course Patients with type 3, subacute, neuronopathic, juvenile Gaucher disease have a relentlessly progressive neurological deterioration and are prime candidates for enzyme replacement and bone marrow replacement 335 OSTEOPETROSIS PRESENTATION There are two main forms, which are approximately equal in incidence – the benign autosomal-dominant form, and the severe autosomal-recessive form Rarely, abnormalities of macrophage-colony stimulating factor (M-CSF) and carbonic anhydrase have been detected Consanguinity is frequent and the gender ratio is equal The milder dominant variety is diagnosed in late childhood and is characterized by dense bones that fracture easily These patients have no specific haematological problems The more severe recessive disorder presents in early infancy with fractures, because of a defect in bone resorption by osteoclasts These patients have large heads, sclerotic bones and hepatosplenomegaly (11.65) They rapidly develop blindness, deafness, cranial nerve palsies and pancytopenia DIAGNOSIS Based on the presence of abnormally sclerotic bones on x-ray and, in the recessive form, by the presence of a leukoerythroblastic blood film 11.64 Gaucher cells in trephine TREATMENT Patients with osteopetrosis must be assessed at a very early stage for bone marrow transplantation, either from a matched sibling donor or from a haploidentical family donor and unrelated donor, before they develop problems such as blindness Symptomatic anaemia and thrombocytopenia are treated with transfusion of red cells and platelets The development of hypersplenism decreases the efficacy of such treatment and splenectomy is required Some patients with the dominant form of the disease have responded transiently to steroid therapy, an effect that is due to reticuloendothelial suppression Ultrasonography can be used to detect increased bone density, fractures, macrocephaly and hydrocephalus prenatally 11.65 Osteopetrosis Blood diseases 336 REFERENCES Hodgkin’s lymphoma Donaldson SS A discourse: The 2002 Wataru W Sutow lecture, Hodgkin Disease in Children – perspectives and progress Med Pediatr Oncol 2003; 40: 73–81 B-cell non-Hodgkin’s lymphoma Magrath I Malignant Non-Hodgkins Lymphoma in Children In: Pizzo PA, Poplach DG (eds) Principles and Practice of Pediatric Oncology (2nd edn) Philadelphia: Lippincott, 1993 T-Cell non-Hodgkin’s lymphoma (NHL)/Leukaemia Hirsch-Ginsberg C, Huh Y, Kagan J et al Advances in the diagnosis of acute leukaemia 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Hematology of Infancy and Childhood (4th edn) Philadelphia: Saunders, 1993 Severe haemophilia A and B (classic haemophilia and Christmas disease) Hathway WE, Goodnight Jr SJ (eds) Disorders of Hemostasis and Thrombosis – a Clinical Guide New York: McGraw Hill, 1993 von Willebrand’s disease (vWD) Lusher JM, Kessler CM (eds) Hemophilia and von Willebrand’s Disease in the 1990s New York: Excerpta Medica, 1991 Thrombocytopaenia with absent radius (TAR) Beardsley DS Platelet Abnormalities in Infancy and Childhood In: Nathan PG, Oski FA (eds) Hematology of Infancy and Childhood (4th edn) Philadelphia: Saunders, 1993 Bernard-Soulier syndrome Blanchette VS, Sparling C, Turner C Inherited Bleeding Disorders In: Hann IM Gibson BES (eds) Baillière’s Clinical Haematology (vol 4) Philadelphia: Baillière Tindall, 1991 Kasabach-Merritt syndrome Bick RL (ed) Perplexing Thrombotic and Hemorrhagic Disorders Hematology/Oncology Clinics of North America (vol 6) Philadelphia: Saunders, 1992 Fanconi anaemia Young NS, Alter BP Clinical Fractures of Fanconi’s Anaemia In: Young NS, Alter BP (eds) Aplastic Anaemia Acquired and Inherited Philadelphia: Saunders, 1994 Dyskeratosis congenita Young NS, Alter BP Dyskeratosis Congenita In: Young NS, Alter BP (eds) Aplastic Anaemia Acquired and Inherited Philadelphia: Saunders, 1994 Transcobalamin II deficiency Chanarin L The Megaloblastic Anaemias (3rd edn) Oxford: Blackwell, 1990 Congenital erythropoietic porphyria Sassa S, Kappas A The Porphyrias In: Nathan DG, Oski FA (eds) Hematology of Infancy and Childhood (4th edn) Philadelphia: Saunders, 1993 Idiopathic pulmonary hemosiderosis Cutz E Idiopathic pulmonaiy hemosiderosis and related disorders in infancy and childhood Perspect Pediatr Pathol 1987; 11: 47–81 Pyruvate kinase deficiency Mentzer WC, Jr Pyruvate Kinase Deficiency and Disorders of Glycolysis In: Nathan DG, Oski FA (eds) Hematology of lnfancy and Childhood Philadelphia: Saunders, 1993 Beta thalassaemia major McDonagh T, Nienhuis AW The Thalassaemia In: Nathan DG, Oski FA (eds) Hematology of Infancy and Childhood Philadelphia: Saunders, 1993 Sickle cell disease Davies SC, Wonke B The Management of Haemoglobinopathies In: Hann IM, Gibson BES (eds) Baillière’s Clinical Hematology (vol 4) Philadelphia: Baillière Tindall, 1991 Hereditary elliptocytosis Becker PS, Lux SE Disorders of the Red Cell Membrane In: Nathan DG, Oski FA (Eds) Hematology of lnfancy and Childhood Philadelphia: Saunders, 1993 Sideroblastic anaemia Will AM Sideroblastic Anaemias In:Lilleyman J, Hann I, Blanchette V (eds) Pediatric Hermatology (2nd edn) Edinburgh: Churchill Livingstone, 1999: 112–115 G6PD deficiency Luzzatto L G6PD defiency and Haemolytic Anaemia In: Nathan DG, Oski FA, (eds) Hematology of lnfancy and Childhood Philadelphia: Saunders, 1993 Leishmaniasis Smith OP, Hann IM, Novelli V et al Visceral leishmanias: rapid response to AmBisome Arch Dis Child 1995; 73: 157–159 Gaucher’s disease Barton NW, Brady RD, Dambrosia JM et al Replacement therapy for inherited enzyme defiency-macrophagetargeted glusocerebrosidase for Gaucher’s disease N Eng J Med 1991; 324: 1464–1470 Cox T, Lachmann R, Hollak C et al Novel oral treatment of Gaucher’s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis Lancet 2000; 355: 1481–1485 Osteopetrosis Lenarsky C, Kohn DB, Weinberg KI et al Bone marrow transplantation for genetic diseases Hematol Oncol Clin N Am 1990; 4: 589–602 ... 11 4 Tetralogy of Fallot (ToF) 11 6 Pulmonary stenosis 11 8 Aortic stenosis 11 9 Cardiomyopathy 12 0 Supraventricular tachycardia (SVT) 12 1 Pericarditis and pericardial... latex 1. 1 Severe anaphylaxis in a 11 -month-old baby caused by bee stings with oedematous eyelids and lips, wheeze and shock 15 16 Emergency Medicine Anaphylaxis may progress slowly or rapidly and. .. drying in the airway 1. 4 Bacterial tracheitis in an 18 -month-old child who presented with a high pyrexia, shock and stridor 18 Emergency Medicine 1. 5 and 1. 6 Inspiratory (left) and expiratory (right)