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Clara Marecos1, 2; Maria Rosário Rodrigues3; Sofia Duarte1

1- Serviço de Neurologia Pediátrica, Área de Pediatria Médica, Hospital Dona Estefânia, Centro Hospitalar Lisboa Central, Lisboa
2- Serviço de Pediatria Hospital Fernando Fonseca, Amadora
3- Patologia Clínica, Laboratório de Bioquímica Genética/Endocrinologia Especial, Hospital Dona Estefânia, Centro Hospitalar Lisboa Central, Lisboa

5th International Symposium on Paediatric Movement Disorders, 2-3 Fevereiro 2017, Barcelona (poster)

Background: Neurotransmitter related disorders are an expanding group of neurometabolic syndromes. Diagnosis is made through detailed clinical assessment, analysis of cerebrospinal fluid pattern (CSF) neurotransmitter metabolites and additional supportive diagnostic investigations. Tyrosine hydroxylase deficiency (TH) is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. This devastating, but treatable neurometabolic disorder, has several presentations on clinical phenotypes and therapeutic approaches. Decreased CSF levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and HVA/5-HIAA ratio, together with normal tyrosine and 5-hydroxyindoleacetic acid (5-HIAA) concentrations are the biochemical diagnostic hallmarks of TH deficiency.
Case report: Eighteen-month-old girl, first child of non-consanguineous parents, born of a term uneventful pregnancy and normal delivery. She was admitted at 6 months of age on the second day of a bronchiolitis due to sudden onset of episodes of global dystonia. On physical exam outside the episodes she presented global hypotonia with poor movements and absence of cervical control, tremor, hyperreflexia in lower limbs striatal toe and developmental delay. There were no signs of parkinsonism or dysautonomia. LCR study showed reduced HVA, MHPG and HVA/5-HIAA ratio, with normal serotonergic pathway, suggestive of tyrosine hydroxylase deficiency. Levodopa 4mg/kg/day was introduced during admission with improvement of dystonic crisis, tremor and interaction. Currently she is on the same therapy. She continues to make slow acquisitions, has a good interaction, smiles, walks, says a few simple words and has sporadic episodes of abnormal. Dystonic postures of the legs. Genetic study revealed a heterozygous mutation in the TH gene (c.698G>A) and a polymorphism in the SLC18A1 gene (previously associated with reduced vesicular monoamine transporter 1 function). MLPA of the TH gene was normal. Exome sequencing is now being performed.
Conclusions: We report a case of a girl with a neurotransmitter profile suggestive of TH deficiency, with hypokinesia, hypotonia, dystonia, tremor and global delay starting in the first year of life. L-dopa was started and clinical improvement was significant, with normal motor development. The CSF signature guided a timely therapeutic intervention with a significant clinical improvement.