(CS11) Levadopa Therapy Resulted In A Significant Motor Recovery In Children With Tyrosine Hydroxylase Deficiency: Three Cases From Hospital Kuala Lumpur

Introduction: Tyrosine hydroxylase (TH) deficiency (OMIM #191290) is an autosomal recessive disorder resulting from impaired cerebral catecholamine neurotransmitters biosynthesis. It has a broad continuous clinical spectrum, manifesting from infancy to adulthood as progressive encephalopathy, abnormal movements including dystonia and Parkinsonism. Early treatment with Levodopa may prevent these devastating manifestations. We reported here 3 patients with TH deficiency, highlighting the challenges in diagnosing this rare condition, and the favourable therapeutic outcome. Case Presentation : Patient 1, male, presented with unexplained psychomotor delay, limb dystonia, truncal hypotonia, feeding difficulties and oculogyric crises since infancy; was initially diagnosed as cerebral palsy. At five-year old, genetic test revealed 2 pathogenic variants of TH gene: c.698G>A [p.(Arg233His)]; c.1293+5G>C. Patient 2, female sibling of Patient 1, diagnosed at 3 years old following family screening. Patient 3, female, developed encephalopathy, and paroxysmal periods of lethargy alternated with irritability at three-month old. Diagnosis remained elusive after consulting multiple doctors. Finally genetic test was performed at five-months old and 2 pathogenic missense variants were identified in TH gene: c.943G>A [p.(Gly315Ser)]; c.1196C>T [p.(Thr399Met)]. All three patients were treated with levodopa, initiated at very low dose, gradually titrated to the maximal beneficial dose. On follow up, all of them showed a significant motor recovery. Patient 1, currently at nine-years old, is able to ambulate with assistance. Patient 2 (now seven years) and Patient 3 (28 months) are able to walk independently. Conclusion : TH deficiency is a treatable disorder if recognized early and should be considered in children with unexplained neurological symptoms