Hyper-beta-alaninemia. Hyperalaninemia.
Incidence
Autosomal recessive. Very rare occurrence.
Clinical Characteristics
Scriver et al. (1966) described a somnolent convulsing male infant who had hyper-beta-alaninemia. Beta amino acids (beta-alanine, beta-amino-isobutyric acid and taurine) were excreted in excess in the urine, probably as a result of an interaction between beta-alanine and a specific cellular transport system with preference for beta-amino compounds. GABA (gamma-amino-butyric acid) was also present in the urine but this was independent of plasma levels of alanine. Postmortem tissues had elevated levels of beta-alanine and carnosine. The authors suggested a defect in beta-alanine-alpha-ketoglutarate transaminase which could expand the free beta-alanine pool and increase tissue carnosine. Beta-alanine is a central nervous system depressant. Inhibition of GABA transaminase and displacement of GABA from central nervous system binding sites may account for GABA-uria and convulsions. The parents were healthy and not related. Three half sibs were normal. One infant died 4 hours after birth with 'breathing trouble.' A fifth pregnancy ended in miscarriage. Higgins et al. (1994) demonstrated hyper-beta-alaninemia and a pyridoxine-responsive deficiency of beta-alanyl-alpha-ketoglutarate transaminase in a 4-year-old girl with intermittent metabolic encephalopathy. Her cultured fibroblasts were more sensitive to low concentrations of beta-alanine than were those of controls. Addition of 0.1 mM of pyridoxine abolished the toxic effects of beta-alanine in the cultures. The patient was treated for 2 years with oral pyridoxine during which time she had no further seizures or somnolence.
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
Aminoacids in serum and urine, quantitative.