Phenylketonuria (PKU), with classic and mild forms (261600*)

Phenylalanine hydroxylase

Biochemical profile: Elevated plasma phenylalanine

Clinical features: Intellectual disability, behavioral problems

Treatment: Dietary phenylalanine restriction, tyrosine supplementation

Dihydropteridine reductase deficiency (261630*)

Dihydropteridine reductase

Biochemical profile: Elevated plasma phenylalanine, high urine biopterin, low plasma biopterin

Clinical features: Similar to mild PKU, but if neurotransmitter deficiency is unrecognized, development of intellectual disability, seizures, and dystonia

Treatment: Dietary phenylalanine restriction, tyrosine supplementation, folinic acid, neurotransmitter replacement

Pterin-4alpha-carbinolamine dehydratase deficiency (264070*)

Pterin-4alpha-carbinolamine dehydratase

Biochemical profile: Elevated plasma phenylalanine, high urine neopterin and primapterin, low plasma biopterin

Clinical features: Similar to mild PKU, but if neurotransmitter deficiency is unrecognized, development of intellectual disability, seizures, and dystonia

Treatment: Dietary phenylalanine restriction, tyrosine supplementation, neurotransmitter replacement

Biopterin synthesis deficiency

GTP-cyclohydrolase (233910*)

Biochemical profile: Elevated plasma phenylalanine, low urine biopterin, low (GCH) or high (PTS and SPR) urine neopterin

Clinical features: Similar to mild PKU, but if neurotransmitter deficiency is unrecognized, development of intellectual disability, seizures, and dystonia

Treatment: Tetrahydrobiopterin and neurotransmitter supplementation

6-Pyruvoyl-tetrahydropterin synthase (261640*)

Sepiapterin reductase (182125*)

Tyrosinemia type I (hepatorenal; 276700*)

Fumarylacetoacetate hydrolase

Biochemical profile: Elevated plasma tyrosine, elevated plasma and urinary succinylacetone

Clinical features: Cirrhosis, acute liver failure, peripheral neuropathy, Fanconi syndrome

Treatment:

Tyrosinemia type II (oculocutaneous; 276600*)

Tyrosine aminotransferase

Biochemical profile: Elevated plasma tyrosine and phenylalanine

Clinical features: Intellectual disability, palmoplantar hyperkeratitis, corneal ulcers

Treatment: Dietary phenylalanine and tyrosine restriction

Tyrosinemia type III (276710, 609695*)

4-Hydroxyphenylpyruvate dioxygenase

Biochemical profile: Elevated plasma tyrosine, elevated urinary 4-hydroxyphenyl derivatives

Clinical features: Developmental delay, seizures, ataxia

Treatment: Dietary phenylalanine and tyrosine restriction, ascorbate supplementation

Transient tyrosinemia of the newborn

4-Hydroxyphenylpyruvate dioxygenase

Biochemical profile: Elevated plasma phenylalanine and tyrosine

Clinical features: Usually occurring in preterm infants; mostly asymptomatic

Occasionally poor feeding and lethargy

Treatment: Tyrosine restriction and ascorbate supplementation for symptomatic patients only

Hawkinsinuria (140350*)

4-Hydroxyphenylpyruvate dioxygenase complex

Biochemical profile: Mild hypertyrosinemia, elevated urinary hawkinsin

Clinical features: Failure to thrive, ketotic metabolic acidosis

Treatment: Dietary phenylalanine and tyrosine restriction, ascorbate supplementation

Alkaptonuria (203500*)

Homogentisate oxidase

Biochemical profile: Elevated urine homogentisic acid

Clinical features: Dark urine, ochronosis, arthritis

Treatment: None; ascorbate supplementation to reduce pigmentation

Oculocutaneous albinism type I (A and B; 203100*)

Tyrosinase

Biochemical profile: No abnormality in plasma and urine amino acids, absent (IA) or decreased (IB) tyrosinase

Clinical features: Absent (IA) or decreased (IB) pigment in skin, hair, iris, and retina; nystagmus; blindness; skin cancer

Treatment: Protection of skin and eyes from actinic radiation