PYRIDOXINE-RESPONSIVE HYPER-BETA-ALANINEMIA ASSOCIATED WITH COHENS SYNDROME

We report intermittent seizures, lethargy, and Cohen's syndrome in a 4 -year-old girl with hyper-beta-alaninemia and a partial deficiency of beta-alanyl-alpha-ketoglutarate transaminase (AKT). To examine the rol e of beta-alanine (beta ALA) in cellular metabolism, we cultured her s kin fibroblasts in medium containing increasing amounts of beta ALA. A t concentrations of 10 to 25 mM, beta ALA caused more than a 50% reduc tion in the growth of her cells compared with normal control skin fibr oblasts. The addition of 0.1 mM of pyridoxine to the culture medium ab olished these toxic effects and increased her skin fibroblast AKT enzy me activity more than twofold. During a 2-year period of clinical obse rvation, there were no further episodes of seizures or somnolence in o ur patient while she received oral pyridoxine therapy.