Central nervous system
Acute encephalopathy
	Mitochondrial disorders (1:30,000)
	CPS deficiency (1:70,000 to 1:100,000)
Acute stroke
	5,10-methylene tetrahydrofolate reductase deficiency (common)
	Fabry's disease (1:80,000 to 1:117,000)
	Ethylmalonic-adipicaciduria (rare)
Agenesis of the corpus callosum
	Mitochondrial disorders (1:30,000; e.g., PDH deficiency [1:200,000])
	Peroxisomal disorders (1:50,000; e.g., Zellweger syndrome, neonatal adrenoleukodystrophy, Refsum's disease)
	Maternal PKU (1:35,000 pregnancies)
	Nonketotic hyperglycinemia (1:250,000 in United States)
	Pyruvate carboxylase deficiency (rare)
Cerebral calcifications
	Adrenoleukodystrophy (1:15,000)
	Mitochondrial disorders (1:30,000)
	GM2 gangliosidosis (rare)
Encephalopathy (rapidly progressive)
	Adenylosuccinate lyase deficiency (rare)
	Atypical PKU (e.g., biopterin defects [rare])
	Molybdenum cofactor deficiency or sulfite oxidase deficiency (both rare)
Macrocephaly
	Hurler's syndrome (MPS I; 1:100,000)
	Neonatal adrenoleukodystrophy (1:100,000)
	Tay-Sachs disease (1:222,000)
	4-hydroxybutyricaciduria (rare)
	Glutaricaciduria, type II (rare)
	l-2-hydroxyglutaricaciduria (rare)
	3-hydroxy-3-methylglutaricaciduriayl (rare)
	Canavan disease (rare)
	Krabbe's disease (rare)
	Mannosidosis (rare)
	Multiple sulfatase deficiency (rare)
Stroke-like episodes
	Ornithine transcarbamylase deficiency(1:70,000)
	Chédiak-Higashi syndrome (rare)
	MELAS syndrome (rare)
Subacute necrotizing encephalomyelopathy (Leigh disease)
	ETC disorders (e.g., complex I deficiency)
	Multiple carboxylase deficiency (e.g., holocarboxylase synthetase [rare]) and biotinidase deficiencies (1:60,000)
	PDH deficiency (1:200,000)
	3-methylglutaconicaciduria (rare)
Fumarase deficiency (rare)
	Pyruvate carboxylase deficiency (rare)
Skin/eye
Angiokeratomas
	Fabry's disease (1:117,000)
	Fucosidosis (rare)
	GM1 gangliosidosis (rare)
	Sialidosis (rare)
Cataracts—lenticular
	Mitochondrial disorders (1:30,000)
	Galactosemia (1:40,000)
	Fabry's disease (1:80,000 to 1:117,000)
	Cerebrotendinous xanthomatosis (rare)
	Galactokinase deficiency (rare)
	Hyperornithinemia (ornithine aminotransferase deficiency; rare)
	Lowe syndrome (rare)
	Lysinuric protein intolerance (rare)
	Mannosidosis (rare)
	Mevalonicaciduria (rare)
Cherry red macula
	Tay-Sachs disease (1:222,000)
	Galactosialidosis (rare)
	GM1 gangliosidosis (rare)
	Mucolipidosis I (rare)
	Multiple sulfatase deficiency (rare)
	Niemann-Pick disease, types A and B (rare)
	Sandhoff's disease (rare)
	Sialidosis (rare)
Corneal opacity
	Fabry's disease (1:80,000 to 1:117,000)
	Hurler's syndrome (MPS I; 1:100,000)
	Cystinosis (1:100,000 to 1:200,000)
	I-cell disease (mucolipidosis II or mucolipidosis III [rare])
	Galactosialidosis (rare)
	GM1 gangliosidosis (rare)
	Mannosidosis (rare)
	Multiple sulfatase deficiency (rare)
Dermatosis
	Acrodermatitis enteropathica (rare)
	Multiple carboxylase deficiency (e.g., holocarboxylase synthetase [rare]) and biotinidase deficiencies (1:60,000)
Hair abnormalities
	Menkes syndrome (rare; e.g., pili torti, trichorrhexis nodosa, monilethrix)
Ichthyosis
	Sjögren-Larsson syndrome (fatty aldehyde dehydrogenase deficiency, < 1:100,000)
	X-linked ichthyosis (1:6,000 boys and men; e.g., steryl-sulfatase deficiency)
Inverted nipples
	Congenital disorders of glycosylation (rare)
	Tetrahydrobiopterin synthesis disorders (rare)
Lens dislocation (ectopia lentis)
	Marfan syndrome (1:10,000)
	Homocystinuria (1:200,000)
	Molybdenum cofactor deficiency or sulfite oxidase deficiency (both rare)
Optic atrophy
	Peroxisomal disorders (1:50,000; Zellweger syndrome, neonatal adrenoleukodystrophy, Refsum's disease)
Xanthomas
	Familial hypercholesterolemia (1:500)
	Lipoprotein lipase deficiency (rare)
	Niemann-Pick disease, types A and B (both rare)
	Cerebrotendinous xanthomatosis (rare)
Muscle/bone/kidney
Arthrosis
	Farber's disease (acid ceramidase deficiency; < 1:40,000)
	Gaucher's disease (1:60,000; type 1–1:900 in Ashkenazi Jews)
	HPRT deficiency (Lesch-Nyhan syndrome; 1:100,000)
	Homocystinuria (1:200,000)
	Alkaptonuria (rare)
Cardiomyopathy
	Hemochromatosis (1:300)
	Fatty acid oxidation disorders (1:10,000)
	Mitochondrial disorders (1:30,000)
	Pompe's disease (1:40,000)
	MPS (1:50,000)
	Glycogenosis, type III (1:125,000)
	D-2-hydroxyglutaricaciduria (rare)
	3-methylglutaconicaciduria (Barth syndrome; rare)
Dysostosis multiplex
	MPS (e.g., Hurler's syndrome [MPS I; 1:100,000], Hunter's syndrome [MPS II; 1:70,000], Sanfilippo's syndrome [MPS III; 1:24,000 in Netherlands, 1:66,000 in United States]; Maroteaux-Lamy syndrome [MPS VI; rare]; Sly's syndrome [MPS VII; rare])
	I-cell disease (mucolipidosis II or mucolipidosis III [rare])
	Multiple sulfatase deficiency (rare)
	Galactosialidosis (rare)
	GM1 gangliosidosis (rare)
Osteoporosis
	Xanthine oxidase deficiency (1:45,000)
	Gaucher's disease, (1:60,000; type 1–1:900 in Ashkenazi Jews)
	Glycogenosis (1:70,000)
	Adenosine deaminase deficiency (1:100,000)
	I-cell disease (mucolipidosis II or mucolipidosis III [rare])
	Refsum's disease
	Lysinuric protein intolerance (rare)
	Menkes syndrome (rare)
Renal calculi
	Cystinuria (1:7,000)
	HPRT deficiency (Lesch-Nyhan syndrome; 1:100,000)
	Adenine phosphoribosyltransferase deficiency (rare)
	Oxaluria (rare)
	Phosphoribosylpyrophosphate synthetase deficiency (rare)
Renal Fanconi syndrome
	Hereditary fructose intolerance (1:20,000 to 1:50,000)
	Mitochondrial disorders (1:30,000; e.g., ETC disorders)
	Galactosemia (1:40,000)
	Wilson's disease (1:50,000)
	Cystinosis (1:100,000 to 1:200,000)
	Type 1 tyrosinemia (rare)
	Lowe syndrome (rare)