Disorder	∼Incidence	Inheritance	Metabolic error	Key manifestation	Key laboratory test	Therapy approach
Amino acid metabolism
Phenylketonuria	1:15,000	Autosomal recessive	Phenylalanine hydroxylase (> 98 percent)	Mental retardation, acquired microcephaly	Plasma phenylalanine concentration	Diet low in phenylalanine hydroxylase
Phenylketonuria	1:15,000	Autosomal recessive	Biopterin metabolic defects (< 2 percent)	Mental retardation, acquired microcephaly	Plasma phenylalanine concentration	Diet low in phenylalanine hydroxylase
Maple syrup urine disease	1:150,000 (1:1,000 in Mennonites)	Autosomal recessive	Branched-chain α-keto acid dehydrogenase	Acute encephalopathy, metabolic acidosis, mental retardation	Plasma amino acids and urine organic acids	Restriction of dietary branched-chain amino acids
Maple syrup urine disease	1:150,000 (1:1,000 in Mennonites)	Autosomal recessive	Branched-chain α-keto acid dehydrogenase		Dinitrophenylhydrazine for ketones	Restriction of dietary branched-chain amino acids
Carbohydrate metabolism
Galactosemia	1:40,000	Autosomal recessive	Galactose 1-phosphate uridyltransferase (most common); galactokinase; epimerase	Hepatocellular dysfunction, cataracts	Enzyme assays, galactose and galactose 1-phosphate assay, molecular assay	Lactose-free diet
Glycogen storage disease, type Ia (von Gierke's disease)	1:100,000	Autosomal recessive	Glucose-6-phosphatase	Hypoglycemia, lactic acidosis, ketosis	Liver biopsy enzyme assay	Corn starch and continuous overnight feeds
Fatty acid oxidation
Medium-chain acyl-CoA dehydrogenase deficiency	1:15,000	Autosomal recessive	Medium-chain acyl-CoA dehydrogenase	Nonketotic hypoglycemia, acute encephalopathy, coma, sudden infant death	Urine organic acids, acylcarnitines, gene test	Avoid hypoglycemia, avoid fasting
Lactic acidemia
Pyruvate dehydrogenase deficiency	1:200,000	X-linked	E₁ subunit defect most common	Hypotonia, psychomotor retardation, failure to thrive, seizures, lactic acidosis	Plasma lactate	Correct acidosis; high-fat, low-carbohydrate diet
Pyruvate dehydrogenase deficiency	1:200,000	X-linked	E₁ subunit defect most common		Skin fibroblast culture for enzyme assay	Correct acidosis; high-fat, low-carbohydrate diet
Lysosomal storage
Gaucher's disease	1:60,000; type 1–1:900 in Ashkenazi Jews	Autosomal recessive	β-glucocerebrosidase	Coarse facial features, hepatosplenomegaly	Leukocyte β-glucocere-brosidase assay	Enzyme therapy, bone marrow transplant
Fabry's disease	1:80,000 to 1:117,000	X-linked	α-galactosidase A	Acroparesthesias, angiokeratomas hypohidrosis, corneal opacities, renal insufficiency	Leukocyte α-galactosidase A assay	Enzyme replacement therapy
Hurler's syndrome	1:100,000	Autosomal recessive	α-l-iduronidase	Coarse facial features, hepatosplenomegaly	Urine mucopolysaccharides Leukocyte α-l-iduronidase assay	Bone marrow transplant
Organic aciduria
Methylmalonicaciduria	1:20,000	Autosomal recessive	Methylmalonyl-CoA mutase, cobalamin metabolism	Acute encephalopathy, metabolic acidosis, hyperammonemia	Urine organic acids Skin fibroblasts for enzyme assay	Sodium bicarbonate, carnitine, vitamin B₁₂, low-protein diet, liver transplant
Propionic aciduria	1:50,000	Autosomal recessive	Propionyl-CoA carboxylase	Metabolic acidosis, hyperammonemia	Urine organic acids	Dialysis, bicarbonate, sodium benzoate, carnitine, low-protein diet, liver transplant
Peroxisomes
Zellweger syndrome	1:50,000	Autosomal recessive	Peroxisome membrane protein	Hypotonia, seizures, liver dysfunction	Plasma very-long-chain fatty acids	No specific treatment available
Urea cycle
Ornithine transcarbamylase deficiency	1:70,000	X-linked	Ornithine transcarbamylase	Acute encephalopathy	Plasma ammonia, plasma amino acids	Sodium benzoate, arginine, low-protein diet, essential amino acids; dialysis in acute stage
					Urine orotic acid
					Liver (biopsy) enzyme concentration