Ornithine-transcarbamoylase (OTC) deficiency (311250*)

OTC

Biochemical profile: Elevated ornithine and glutamine, decreased citrulline and arginine, markedly increased urine orotate

Clinical features: In males, recurrent vomiting, irritability, lethargy, hyperammonemic coma, cerebral edema, spasticity, intellectual disability, seizures, death

In female carriers, variable manifestations, ranging from growth delay, small stature, protein aversion, and postpartum hyperammonemia to symptoms as severe as those in males with the deficiency

Treatment: Hemodialysis for emergent hyperammonemic crisis, sodium benzoate, sodium phenylacetate, sodium phenylbutyrate, low-protein diet supplemented with essential amino acid mixture and arginine, citrulline

Experimental attempts at gene therapy, liver transplantation (which is curative)

N-Acetylglutamate synthetase deficiency (237310*)

N-Acetylglutamate synthetase

Biochemical profile: Similar to OTC deficiency except for normal to low urine orotate

Clinical features: Similar to OTC deficiency except carriers are asymptomatic

Treatment: Similar to OTC deficiency but also N-carbamylglutamate supplementation

Carbamoyl phosphate synthetase (CPS) deficiency (237300*)

Carbamoyl phosphate synthetase

Biochemical profile: Similar to OTC deficiency except for normal to low urine orotate

Clinical features: Similar to OTC deficiency except carriers are asymptomatic

Treatment: Sodium benzoate and arginine

Citrullinemia type I (215700*)

Argininosuccinic acid synthetase

Biochemical profile: High plasma citrulline and glutamine, citrullinuria, orotic aciduria

Clinical features: Episodic hyperammonemia, growth failure, protein aversion, lethargy, vomiting, coma, seizures, cerebral edema, developmental delay

Treatment: Similar to that for OTC deficiency except citrulline supplementation is not recommended

Liver transplantation

Citrullinemia type II (603814*, 603471*)

Citrin

Biochemical profile: Elevated plasma citrulline, methionine, galactose, and bilirubin

Clinical features: With neonatal onset, cholestasis resolved by 3 months

With adult onset, enuresis, delayed menarche, sleep reversal, vomiting, delusions, hallucinations, psychosis, coma

Treatment: Liver transplantation; otherwise no clear treatment

Argininosuccinic aciduria (207900*)

Argininosuccinate lyase

Biochemical profile: Elevated plasma citrulline and glutamine, elevated urine argininosuccinate

Clinical features: Episodic hyperammonemia, hepatic fibrosis, elevated liver enzymes, hepatomegaly, protein aversion, vomiting, seizures, intellectual disability, ataxia, lethargy, coma, trichorrhexis nodosa

Treatment: Arginine supplementation

Argininemia (107830*)

Arginase I

Biochemical profile: Elevated plasma arginine, diaminoaciduria (argininuria, lysinuria, cystinuria, ornithinuria), orotic aciduria, pyrimidinuria

Clinical features: Growth and developmental delay, anorexia, vomiting, seizures, spasticity, irritability, hyperactivity, protein intolerance, hyperammonemia

Treatment: Low-protein diet, benzoate, phenylacetate, liver transplantation

Lysinuric protein intolerance (dibasic aminoaciduria II; 222700*)

Dibasic amino acid transporter

Biochemical profile: Elevated urine lysine, ornithine, and arginine

Clinical features: Protein intolerance, episodic hyperammonemia, growth and developmental delay, diarrhea, vomiting, hepatomegaly, cirrhosis, leucopenia, osteopenia, skeletal fragility, coma

Treatment: Low-protein diet, citrulline

Hyperornithinemia, hyperammonemia, and homocitrullinemia (238970*)

Mitochondrial ornithine translocase

Biochemical profile: Elevated plasma ornithine, homocitrullinemia

Clinical features: Intellectual disability, progressive spastic paraparesis, episodic confusion, hyperammonemia, dyspraxia, seizures, vomiting, retinopathy, abnormal nerve conduction and evoked potentials, leukodystrophy

Treatment: Lysine, ornithine, or citrulline supplementation

Ornithinemia (258870*)

Ornithine aminotransferase

Biochemical profile: Elevated plasma ornithine and urine ornithine, lysine, and arginine; low plasma lysine, glutamic acid, and glutamine

Clinical features: Myopia, night blindness, blindness, progressive loss of peripheral vision, progressive gyrate atrophy of choroid and retina, mild proximal hypotonia, myopathy

Treatment: Pyridoxine, low-arginine diet, lysine and alpha-aminoisobutyrate to increase renal loss of ornithine; proline or creatine supplementation

Hyperinsulinism-hyperammonemia syndrome (606762*)

Hyperactivity of glutamate dehydrogenase

Biochemical profile: Elevated urine alpha-ketoglutarate

Clinical features: Seizures, recurrent hypoglycemia, hyperinsulinism, asymptomatic hyperammonemia

Treatment: Prevention of hypoglycemia