Metabolic disorders

Cystathionine beta-synthase

Marfanoid habitus, DOWNWARD lens dislocation, thrombosis, intellectual disability, osteoporosis

Galactocerebrosidase

Optic atrophy, peripheral neuropathy, globoid cells, developmental regression

ALA dehydratase and ferrochelatase

Microcytic anaemia with basophilic stippling, abdominal colic, wrist/foot drop, encephalopathy, gingival lead lines

Multiple ETC / PDC subunits

Subacute necrotising encephalomyelopathy; brainstem and basal ganglia lesions

Hypoxanthine-guanine phosphoribosyltransferase

Hyperuricaemia, gout, orange sand in nappies, self-mutilation, choreoathetosis, intellectual disability

Branched-chain alpha-ketoacid dehydrogenase

Burnt-sugar/maple urine odour, poor feeding, ketoacidosis, encephalopathy

Medium-chain acyl-CoA dehydrogenase

Hypoketotic hypoglycaemia on fasting, vomiting, coma, SIDS-like death

Myophosphorylase

Exercise intolerance, cramps, myoglobinuria, second-wind phenomenon; normal blood glucose

Mitochondrial tRNA-Leu(UUR) mutation (commonly m.3243A>G); impairs synthesis of mtDNA-encoded respiratory subunits, Complex I most severely

Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes; ragged red fibres

Arylsulfatase A

Central and peripheral demyelination, ataxia, dementia

Methylmalonyl-CoA mutase (or cobalamin handling)

Ketoacidosis, hyperammonaemia, failure to thrive

Acid sphingomyelinase

Hepatosplenomegaly, cherry-red macula, neurodegeneration (type A), foam cells

Tyrosinase

Hypopigmentation of skin/hair/eyes, photophobia, nystagmus, high skin cancer risk

Ornithine transcarbamylase

Commonest urea cycle defect; hyperammonaemia, vomiting, encephalopathy; low BUN, no megaloblastic anaemia

Phenylalanine hydroxylase (or BH4 synthesis/recycling)

Intellectual disability, musty odour, hypopigmentation, eczema, seizures