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Aromatic L-amino acid decarboxylase deficiency

Clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis

Department of Child Health (Drs. Hyland, Surtees, and Clayton), Institute of Child Health, London, UK; and the Institute of Obstetrics and Gynaecology (Dr. Rodeck), London, UK.

We report the clinical features, biochemical details, and treatment of the first detected cases of an inborn error of aromatic L-amino acid decarboxylase. Male monozygotic twins presented with extreme hypotonia and oculogyric crises. Concentrations of biogenic amines and their metabolites were reduced considerably both centrally and peripherally. Pterin and phenylalanine metabolism were normal. Activity of aromatic L-amino acid decarboxylase was virtually absent in a liver biopsy sample and greatly reduced in plasma. Concentrations of L-dopa, 3-methoxytyro-sine, and 5-hydroxytryptophan were elevated in CSF, plasma, and urine. CSF S-adenosylmethionine concentrations were reduced. Pyridoxine treatment had no clinical effect but led to a fall in CSF L-dopa and 3-methoxytyrosine and a rise in S-adenosylmethionine. Treatment with either bromocriptine or tranylcypromine stopped the abnormal eye movements; tranylcypromine treatment also improved muscle tone and led to a rise in plasma norepinephrine and whole blood serotonin. Combined treatment with pyridoxine, bromocriptine, and tranylcypromine produced sustained improvement in tone and voluntary movements. The twins' parents were asymptomatic but had reduced plasma aromatic L-amino acid decarboxylase activity, consistent with heterozygosity. We monitored a subsequent pregnancy through biochemical analyses of a fetal liver biopsy sample and of amniotic fluid. We predicted an unaffected fetus, which was confirmed clinically and biochemically after birth.

Address correspondence and reprint requests to Dr. Keith Hyland, Baylor Research Institute, 3812 Elm Street, P.O. Box 710699, Dallas, TX 75226.

K.H. was supported by Action Research for the Crippled Child, and R.S. by the Wellcome Trust.

Received October 22, 1991. Accepted for publication in final form March 27, 1992.

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