Beta-Amino Acid and Gamma-Amino Acid Disorders

Hyper-beta-alaninemia (237400*)

Beta-alanine-alpha-ketoglutarate aminotransferase

Biochemical profile: Elevated urinary beta-alanine, taurine, GABA, and beta-aminoisobutyrate

Clinical features: Seizures, somnolence, death

Treatment:Pyridoxine

Methylmalonate/malonate semialdehyde dehydrogenase deficiency with 3-amino and 3-hydroxy aciduria (236795*)

Methylmalonate/malonate semialdehyde dehydrogenase

Biochemical profile: Elevated 3-hydroxyisobutyrate 3-aminoisobutyrate, 3-hydroxypropionate beta-alanine, and 2-ethyl-3-hydroxypropionate

Clinical features: None to mild

Treatment: Not determined

Methylmalonic semialdehyde dehydrogenase deficiency with mild methylmalonic acidemia

Methylmalonic semialdehyde dehydrogenase (see also Branched-chain amino acid metabolism)

Biochemical profile: Moderately elevated urine methylmalonate

Clinical features: Developmental delay, seizures

Treatment: No effective treatment

Hyper-beta-aminoisobutyric aciduria (210100*)

D(R)-3-Aminoisobutyrate:pyruvate aminotransferase

Biochemical profile: Elevated beta-aminoisobutyric acid

Clinical features: Benign

Treatment: None needed

Pyridoxine dependency with seizures (266100*)

Not determined

Biochemical profile: Elevated cerebrospinal fluid glutamate

Clinical features: Seizure disorder refractory to conventional anticonvulsants, high-pitched cry, hypothermia, jitteriness, dystonia, hepatomegaly, hypotonia, dyspraxia, developmental delay

Treatment:Pyridoxine

GABA-transaminase deficiency (137150*)

4-Aminobutyrate-alpha-ketoglutarate aminotransferase

Biochemical profile: Elevated plasma and cerebrospinal fluid GABA and beta-alanine, elevated carnosine

Clinical features: Accelerated linear growth, seizures, cerebellar hypoplasia, psychomotor delay, leukodystrophy, burst suppression electroencephalographic pattern

Treatment: No known treatment

4-Hydroxybutyric aciduria (271980*)

Succinic semialdehyde dehydrogenase

Biochemical profile:Elevated urinary 4-hydroxybutyrate and glycine

Clinical features: Psychomotor retardation, speech delay, hypotonia

Treatment:Vigabatrin

Carnosinemia (212200*), homocarnosinosis (236130*), or both

Carnosinase

Biochemical profile: In carnosinemia phenotype, carnosinuria despite meat-free diet, elevated urine anserine after ingestion of food containing imidazole dipeptides, normal cerebrospinal fluid

In homocarnosinosis phenotype, elevated cerebrospinal fluid homocarnosine, normal serum carnosine

Clinical features: Usually benign; reported symptoms probably due to ascertainment bias

Treatment: None needed