SUCCESSFUL PREGNANCY IN A NEW PATIENT WITH EARLY ONSET DOPA-RESPONSIVE DYSTONIA DUE TO AUTOSOMAL RECESSIVE GTP CYCLOHYDROLASE (AR GTP-CH) DEFICIENCY WITHOUT HYPERPHENYLALANINEMIA

Background: The effect of pregnancy as well as treatment in genetically confirmed AR GTP-CH deficiency has never been reported. Case report: We report the first case of pregnancy in a 27-year-old woman with this disorder. Since the age of 2 she presented progressive generalized rigidity, limb and cervical dystonia with diurnal fluctuation. At the age of 7 CSF examination showed: neopterin 4 nmol/L (r.v. 9-20), biopterin 13 nmol/L (r.v 10-30), normal homovanillic acid and 5- hydroxyindoleacetic acid. Neopterin and biopterin (mmol/mol Creatinine) were low in urine (0.1 r.v. 0.3-4.0, and 0.24 r.v. 0.5-3.0, respectively). Blood phenylalanine (Phe) was persistently normal, whereas oral Phe loading test revealed a severely impaired Phe clearance. GCH1 gene examination detected two novel missense mutations involving exon 3 (c.508A>G; R170G) and exon 6 (c.745A>G; R249G), which were transmitted by the proband father and mother, respectively. L-Dopa/Carbidopa treatment (10 mg/kg/day) started promptly, normalised neurological status. She became pregnant when 25. L-Dopa/Carbidopa dosage was reduced to 2 mg/kg/day. She delivered a healthy male infant, who was heterozygous for exon 3 mutation and showed a mild transient trunk dystonia during the first 2 years of life. Conclusion: Normal pregnancy and delivery as well as levodopa-carbidopa therapy are compatible with AR GTP-CH deficiency condition.