THÔNG TIN TÀI LIỆU
TABLE 95.2 CLINICAL AND LABORATORY FINDINGS OF INBORN ERRORS OF METABOLISM Most IEMs are autosomal recessive in their inheritance, but they may be X-linked, mitochondrial, or, uncommonly, autosomal dominant A family history of either known metabolic disease or unusual medical presentations (e.g., death due to neurologic, cardiac, and/or hepatic dysfunction; sepsis; or unexplained neonatal or sudden infant deaths in siblings or maternal male relatives) should increase suspicion for an underlying metabolic disease Maternal illness during pregnancy, particularly acute fatty liver of pregnancy or HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, may be due to maternal heterozygosity for a fatty acid oxidation defect, specifically 3-hydroxyacyl-CoA dehydrogenase deficiency A negative family history and negative NBS not rule out an IEM It is important to note that NBS varies from state-to-state and not all IEMs are part of the screen For example, several urea cycle disorders (ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase deficiency) are not detectable by NBS It is also worth keeping in mind that the results of the NBS are often not available in the first several days of life Neonate (5 years of age, adolescent, or adult In the older child, adolescent, or adult, undiagnosed metabolic disease should be considered in individuals with subtle neurologic or psychiatric abnormalities which may present with a history waxing/waning symptoms that have been attributed to other causes Most typically, these individuals are diagnosed as having birth injury, behavioral problems, attention deficit hyperactivity disorder, psychiatric disorders, or atypical forms of medical diseases such as multiple sclerosis, migraines, epilepsy, or stroke The more common findings include mild to profound developmental delay, autism, and learning disabilities Manifestations may be intermittent, precipitated by the stress of illness or dietary changes or fasting, or may be progressive For example, partial ornithine transcarbamylase deficiency can present in as a life-threatening encephalopathy in an adolescent female who has a history of protein aversion, migraine-like headaches, vomiting, abdominal pain, lethargy, and behavioral problems, and who has consumed a large amount of protein Fatty acid oxidation defects may also present in adolescence with sudden death or life-threatening cardiac arrhythmia, hypoketotic hypoglycemia, and/or rhabdomyolysis Glycogen storage disorders often present in adolescents as exercise intolerance, muscle weakness, cramping, and/or rhabdomyolysis because of their greater participation in sports during these years Some mitochondrial disorders present during adolescence or adulthood with loss of vision and/or hearing, cardiac dysfunction, myopathy, neurologic degeneration, and endocrine disturbances Stroke or stroke-like episodes with or without encephalopathy may occur with aminoacidopathies, in particular homocystinuria, urea cycle defects, organic acidemias, disorders of carbohydrate metabolism, and mitochondrial disorders, most notably mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) Disorders in which psychiatric disturbances may be the initial presenting manifestation include homocystinuria; urea cycle defects, especially partial ornithine transcarbamylase deficiency; lysosomal storage disorders; peroxisomal disorders; and Wilson disease, a disorder of copper metabolism Patients with phenylketonuria who are no longer on a low-protein diet may also manifest psychiatric symptoms Physical Examination IEMs can affect any organ system ( Table 95.1 ), and often affect multiple organ systems, and therefore should be considered in patients who present with altered level of consciousness, encephalopathy, cardiac failure, hepatic failure, skeletal muscle myopathy, weakness and/or cramping, and/or neuropsychiatric disturbance Physical examination may be normal, have subtle and/or nonspecific findings, or have findings that provide more specific diagnostic information ( Table 95.2 ) Findings tend to be related to abnormal anatomic proportion (i.e., size and shape), rather than to major structural defects and usually become more pronounced over time Some disorders have characteristic facies, short stature, organomegaly, and/or musculoskeletal abnormalities IEMs within each major category are listed in Table 95.3 Features of specific IEMs can be found in texts referenced at the end of this chapter and on various websites, including the National Center for Biotechnology Information’s “Online Mendelian Inheritance in Man” website (http://www.ncbi.nlm.nih.gov/omim ) TABLE 95.3 SPECIFIC INBORN ERRORS OF METABOLISM BY CATEGORY a
Ngày đăng: 22/10/2022, 11:13
Xem thêm: