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Pyridoxine-responsive hyper-ß-alaninemia associated with Cohen's syndrome

Clinical Neurogenetics Unit, Clinical Neuroscience Branch (Dr. Higgins) and the Developmental and Metabolic Neurology Branch (Drs. Brady and Barton, and C.R. Kaneski), National Institute of Neurological Disorders and Stroke, and the Human Genetics Branch (I. Bernardini), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

We report intermittent seizures, lethargy, and Cohen's syndrome in a 4-year-old girl with hyper-ß-alaninemia and a partial deficiency of ß-alanyl--ketoglutarate transaminase (AKT). To examine the role of ß-alanine (ßALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of ßALA. At concentrations of 10 to 25 mM, ßALA caused more than a 50% reduction in the growth of her cells compared with normal control skin fibroblasts. The addition of 0.1 mM of pyridoxine to the culture medium abolished these toxic effects and increased her skin fibroblast AKT enzyme activity more than twofold. During a 2-year period of clinical observation, there were no further episodes of seizures or somnolence in our patient while she received oral pyridoxine therapy.

Address correspondence and reprint requests to Dr. Joseph J. Higgins, Clinical Neurogenetics Unit, Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5N214, Bethesda, MD 20892.

Received December 15, 1993. Accepted in final form February 17, 1994.

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