Pediatric emergency medicine trisk 607

Aminoacidopathies Alkaptonuria Cystinuria types I–III Hartnup disease Hawkinsinuria Histidinemia Homocystinuria types Ia, Ib, II Nonketotic hyperglycinemia Phenylketonuria Tyrosinemia types I–III Organic acidemias b 3-Hydroxy-3-methylglutaric aciduria 3-Methylcrotonylglycinuria 3-Methylglutaconic aciduria types I–IV Biotinidase deficiency Glutaric acidemia type I Holocarboxylase synthetase deficiency Hydroxyglutaric aciduria Isovaleric acidemia Maple syrup urine disease Methylmalonic acidemia Propionic acidemia types I, II β-Ketothiolase deficiency Urea cycle defects and disorders of ammonia detoxification Urea cycle defects Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase deficiency Citrullinemia N-acetyl glutamate synthetase deficiency Ornithine transcarbamylase deficiency Hepatic amino acid transport Homocitrullinuria, hyperornithinemia, and hyperammonemia (HHH) syndrome Lysinuric protein intolerance Fatty acid oxidation defects Carnitine palmitoyltransferase deficiency types I, II Carnitine transporter deficiency Carnitine-acylcarnitine translocase deficiency Hydroxymethylglutaryl-CoA (HMG-CoA) lyase deficiency, HMG-CoA synthetase deficiency Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency Medium-chain 3-ketoacyl thiolase (MCKAT) deficiency Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency Short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency Short-chain acyl-CoA dehydrogenase (SCAD) deficiency Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency Disorders of carbohydrate metabolism Carbohydrate intolerance disorders Galactosemia Galactokinase deficiency Hereditary fructose intolerance Fructosuria Fructose-1,6-diphosphatase deficiency Carbohydrate production/utilization disorders Glycogen storage disorder types 0, Ia (von Gierke), Ib/c, Ic, II (Pompe), IIb, III (Cori or Forbes), IV (Anderson), V (McArdle), VI (Hers), VII (Tarui), VIII, IX, X, XI Lysosomal storage disorders Mucopolysaccharidosis (MPS) MPS IH (Hurler), IH/S (Hurler–Scheie), IS (Scheie), MSII (Hunter), IIIA–D (Sanfilippo), IVA, B (Morquio), VI (Maroteaux–Lamy), VII (Sly) Sphingolipidoses Canavan disease Fabry disease Farber disease Gaucher disease types I–III GM1 gangliosidosis types 1–3 GM2 gangliosidosis types (Tay–Sachs), (Sandhoff) GM3 gangliosidosis Krabbe disease Metachromatic leukodystrophy—infantile, juvenile, adult Multiple sulfatase deficiency Niemann–Pick disease—types IS, IC, IIA, IIS, IIC Oligosaccharidoses (glycoproteinoses) Aspartylglucosaminuria Fucosidosis types I, II Galactosialidosis Mannosidosis α types I, II, β Pycnodysostosis (Maroteaux–Lamy III) Schindler disease Sialidosis types I, II (previously mucolipidosis I) Sialolipidosis Mucolipidosis Mucolipidosis types II (I-cell), III (pseudo-Hurler), IV Mitochondrial disorders 2-Ketoglutarate dehydrogenase complex deficiency Friedreich ataxia Fumarase deficiency Glutaric acidemia type II Kearns–Sayre syndrome Leigh disease Mitochondrial encephalomyopathy lactic acidosis stroke-like episodes Myoclonic epilepsy, ragged red fiber disease Pearson syndrome Phosphoenolpyruvate carboxylase deficiency Pyruvate carboxylase deficiency Pyruvate dehydrogenase complex deficiency Succinate dehydrogenase deficiency Peroxisomal disorders Adrenomyeloneuropathy Adrenoleukodystrophy in neonatal, adult Catalase deficiency Glutaric acidemia type III Leber hereditary optic neuropathy Refsum disease infantile, adult Rhizomelic chondrodysplasia punctata Wolfram syndrome Zellweger syndrome Congenital disorders of glycosylation Disorders of metal transport Disorders of heme metabolism Disorders of nucleic acid metabolism Disorders of cholesterol synthesis Disorders of bile acid synthesis Disorders of neurotransmitter metabolism Laboratory Findings In the patient with potentially life-threatening symptoms, evaluation for possible IEM should be initiated immediately The initial laboratory evaluation of a patient with suspected IEM includes electrolytes, glucose, venous blood gas, CBC, ammonia, lactate, blood urea nitrogen (BUN), creatinine, liver tests (aspartate transaminase [AST] and alanine transaminase [ALT], prothrombin time [PT], partial thromboplastin time [PTT]), uric acid and urinalysis If possible, the initial evaluation should also include samples for specialized testing including plasma amino acids, urine organic acids, and acylcarnitine profile ( Table 95.4 ) In addition to these studies, patients with history or physical examination suggestive of myopathy should have lactate dehydrogenase, aldolase, creatinine phosphokinase, and urine myoglobin measured as part of their initial screen If a metabolic disease is suspected, consultation with an IEM specialist should be considered to guide further laboratory evaluation and assist with the appropriate collection and processing of specimens Blood should be collected and sent for plasma amino acids and acylcarnitine profile, while urine should be collected for potential analysis of organic acids, acylglycine, and/or orotic acid ( Table 95.5 ) Additional blood and urine for possible further testing should be obtained and stored Cerebrospinal fluid (CSF), if obtained, should be collected at the same time as plasma and immediately frozen and stored for possible further testing for neurometabolic disorders, most commonly nonketotic hyperglycinemia, disorders of serine biosynthesis, and/or neurotransmitter disorders Measurement of lactate and pyruvate are important components of the ED evaluation but may be difficult to interpret, particularly in the patient with hypoxia, poor perfusion, seizure, and/or sepsis Laboratory abnormalities are often transient, particularly if fluids and/or glucose are administered; therefore, normal values not rule out an IEM It is critical to obtain pretreatment specimens, if possible If pretreatment specimens were not obtained, as is often the case because many IEMs are first suspected based on results of routine laboratory studies, discarded pretreatment samples are likely to be more informative than those collected after therapy Collection of samples during acute illness is usually preferred to provocative testing by metabolic challenge performed when the child is otherwise well because this method may not yield diagnostic specimens and may be dangerous The confirmatory specific diagnosis of most IEMs requires additional specialized testing for abnormal metabolites, perturbed enzymatic function, or molecular testing When a child dies in the ED and an IEM is suspected, it is extremely important to attempt to diagnose that disease because of the possibility that asymptomatic family members are affected or future children are at risk Routine autopsy does not usually provide a definitive diagnosis of IEM but may rule out other causes of death and offer clues IEMs can be diagnosed in the child who has just died by collecting the appropriate specimens ( Table 95.6 ) In some situations, exome sequencing, genome sequencing, or metabolomics may be used to evaluate for an underlying cause of decompensation This evaluation is usually guided by specialty consultation Most IEMs can be categorized based on findings of initial laboratory evaluations Nearly all patients with IEMs that present as acute life-threatening disease will have hypoglycemia, metabolic acidosis, and/or hyperammonemia These initial findings will guide immediate treatment and further evaluation Important exceptions are nonketotic hyperglycinemia (usually presents within 48 hours of birth with lethargy, coma, seizures, hypotonia, spasticity, hiccups, and apnea) and pyridoxine deficiency and folinic acid–responsive disorders (which present with intractable seizures with or without encephalopathy as neonate)