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A variety of inherited systemic conditions cause different types of disease-producing chemical imbalances affecting essentially all organs to some degree; these conditions are called inborn errors of metabolism and also are termed inherited metabolic disorders.1–16 Each is characterized by a specific genetic defect resulting in an abnormality of an enzyme necessary for the degradation of a chemical substance.2,6 The disruption of the chemical constituent’s degradation results in disease by causing either a deficiency of a substance or a pathologic accumulation of a substance.1,2,6,9 The first of these disorders was identified by Sir Archibald Garrod, who coined the term inborn errors of metabolism in 1902.14 There are currently more than 600 inborn errors of metabolism that have been discovered.2,15
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Each specific inborn error of metabolism is rare, but overall, approximately 1 in 1000 people are affected.1,2,6 Most show autosomal recessive inheritance; however, X-linked recessive inheritance occurs, and, less commonly, autosomal dominant inheritance.9 Most of these diseases arise in children; however, with the identification of attenuated variants, and with continuing improved survival, some of the conditions must be considered in any-age patients.1,2,6
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Inborn errors of metabolism often present with unexpected findings and lead to a high clinical suspicion. Fast and accurate radiologic diagnosis and clinical–radiologic correlation are critical for successful therapy because newer and more effective approaches are being designed and require early diagnosis.2,6 While specialists with expertise in various inborn errors of metabolism are found in academic institutions, primary care physicians and pediatricians are frequently the first physicians to encounter these patients.9
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Some conditions fall into a few broad groups, including disorders of amino acid metabolism, organic acidurias, urea cycle defects, disorders of ketogenesis and ketolysis, disorders of fatty acid oxidation, lysosomal storage disorders, and mitochondrial disease.2,6 The lung is rarely a primary site of clinical disease in these patients; however, pulmonary involvement occurs in many of the disorders, resulting in clinically significant lung disease in some.2,5,16 Pulmonary infections are not an uncommon secondary feature in many inborn errors of metabolism. This chapter highlights some specific inborn errors of metabolism in which lung disease may be a clinically significant feature.
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ACID SPHINGOMYELINASE DEFICIENCY (NIEMANN-PICK DISEASE TYPES A AND B)
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An autosomal recessive condition, acid sphingomyelinase (ASM) deficiency, has a phenotype that occurs in a continuum. Niemann-Pick disease type A (NPA) shows severe, neuropathic disease with early symptoms, resulting in death in infancy or early childhood. Niemann-Pick disease type B (NPB) shows nonneuropathic disease with generally later onset and milder symptoms.1–4,17–25 Patients with NPA typically develop hepatosplenomegaly by approximately 3 months of age. Hepatosplenomegaly may become massive and is often fatal within 3 years. ...