Organic Acidurias Inborn errors of metabolism leading to accumulation of organic acids. As a group, common cause of infantile encephalopathy due to inherited metabolic diseases. Rapid diagnosis crucial: some curable;…

Peroxisomal Diseases: Adrenoleukodystrophy, Zellweger Syndrome, Refsum Disease Peroxisomal functions: degrade very long chain fatty acids (VLCFA); initiate synthesis of plasmalogens (myelin sheath lipids). Classification Peroxisome biogenesis disorders: abnormalities in more…

Hyperammonemia Causes of high blood ammonia levels: Table 88.1. Differential diagnosis differs according to age of patient. Table 88.1 Major Causes of Hyperammonemia Newborn Period Asymptomatic infant    Transient hyperammonemia of the…

Disorders of DNA Maintenance, Transcription, and Translation May be caused by abnormality in: (1) DNA repair following exposure to mutagens (nucleotide excision repair); (2) DNA duplication and transcription, (3) RNA…

Glucose Transporter Type 1 Deficiency Syndrome Clinical features: usual presentation is with seizures in early infancy. Variable features: delayed motor development, microcephaly, ataxia, hypotonia, spasticity. Isolated mental retardation or choreoathetosis…

Disorders of Carbohydrate Metabolism Glycogen Storage Diseases Abnormal metabolism of glycogen, glucose. Due to specific enzyme deficiency (Table 85.1). May present with: fasting hypoglycemia, pathologic glycogen storage (e.g., hepatomegaly), or…

Lysosomal and Other Storage Diseases Storage material (complex lipid, saccharide, or protein) accumulates in lysosomes due to genetically determined deficiency of a catabolic enzyme. Inheritance recessive, usually autosomal, occasionally X-linked….

Disorders of Purine and Pyrimidine Metabolism Purines and pyrimidines: heterocyclic compounds with important roles in nucleotide synthesis, generation of energy compounds (ADP, ATP), signaling pathways (cyclic AMP). Several distinct disorders…

Disorders of Amino Acid Metabolism Incidence: phenylketonuria 1:10,000; defective amino-acid transport 2:10,000; all other aminoacidopathies <8:100,000. Neurologic damage frequently preventable with early treatment; mass newborn screening important for early diagnosis….

Chromosomal Diseases Abnormal total number of chromosomes (aneuploidy) or structural rearrangement (deletion, translocation, duplication). Clinical manifestations: mental retardation (most common), variable congenital malformations. Trisomy 21 (Down Syndrome) Extra copy of…