Novel mutations in the tyrosine hydroxylase gene in the first Czech patient with tyrosine hydroxylase deficiency.
Tyrosine hydroxylase deficiency manifests mainly in early childhood             and includes two clinical phenotypes: an infantile progressive hypokinetic-rigid             syndrome with dystonia (type A) and a neonatal complex encephalopathy (type B).             The biochemical diagnostics is exclusively based on the quantitative determination             of the neurotransmitters or their metabolites in cerebrospinal fluid (CSF). The             implementation of neurotransmitter analysis in clinical praxis is necessary for early             diagnosis and adequate treatment. Neurotransmitter metabolites in CSF were             analyzed in 82 children (at the age 1 month to 17 years) with clinical suspicion for             neurometabolic disorders using high performance liquid chromatography (HPLC)             with electrochemical detection. The CSF level of homovanillic acid (HVA) was             markedly decreased in three children (64, 79 and 94 nmol/l) in comparison to             age related controls (lower limit 218-450 nmol/l). Neurological findings including             severe psychomotor retardation, quadruspasticity and microcephaly accompanied             with marked dystonia, excessive sweating in the first patient was compatible with             the diagnosis of tyrosine hydroxylase (TH) deficiency (type B) and subsequent             molecular analysis revealed two novel heterozygous mutations c.636A>C and             c.1124G>C in the TH gene. The treatment with L-DOPA/carbidopa resulted in the             improvement of dystonia. Magnetic resonance imaging studies in two other patients             with microcephaly revealed postischaemic brain damage, therefore secondary             HVA deficit was considered in these children. Diagnostic work-up in patients with             neurometabolic disorders should include analysis of neurotransmitter metabolites in             CSF.
Department of Pediatrics and Adolescent Medicine, Charles University, Prague, Czech Republic.
K
K
Szentiványi
H
H
Hansíková
J
J
Krijt
K
K
Vinšová
M
M
Tesařová
E
E
Rozsypalová
P
P
Klement
J
J
Zeman
T
T
Honzík
D000293:Adolescent; D001928:Brain Diseases, Metabolic / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D020821:Dystonic Disorders / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency* / Q000235:genetics*
D018377:Neurotransmitter Agents; D014446:Tyrosine 3-Monooxygenase