Dhashene Gunaseelan1*, Farah Asyfatin Johari1, Yusnita Yakob2, Lock-Hock Ngu1
1. Department of Genetics, Kuala Lumpur Hospital, Ministry of Health Malaysia, Jalan Pahang, 50588 Kuala Lumpur, Malaysia
2. Molecular Diagnostics Unit, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Jalan Pahang, 50588 Kuala Lumpur, Malaysia
*Corresponding author: Dhashene Gunaseelan, Department of Genetics, Kuala Lumpur Hospital, Ministry of Health Malaysia, Jalan Pahang, 50588 Kuala Lumpur, Malaysia,
CITATION: Gunaseelan D, Johari FA, Yakob Y, Ngu LH. Levodopa therapy resulted in significant motor recovery in children with tyrosine hydroxylase deficiency: a case series. International Medical Research Journal. 2023 Jun;9(1):63–9.
ABSTRACT
Tyrosine hydroxylase (TH) deficiency (OMIM #191290) is an autosomal recessive disorder resulting from impaired biosynthesis of cerebral catecholamine neurotransmitters. It has a broad continuous clinical spectrum, manifesting from infancy to adulthood as progressive encephalopathy, as well as abnormal movements including dystonia and Parkinsonism. Early treatment with Levodopa may prevent these devastating manifestations. We hereby report three patients with TH deficiency, highlighting the challenges in diagnosing this rare condition, and the favourable therapeutic outcomes. The first patient is a male, presented with unexplained psychomotor delay, limb dystonia, truncal hypotonia, feeding difficulties and oculogyric crises since infancy; was initially diagnosed as cerebral palsy. At the age of 5, a genetic test revealed 2 pathogenic variants of TH gene: c.698G>A [p.(Arg233His)]; c.1293+5G>C. The second patient is the female sibling of the first patient; diagnosed at 3 years old upon family screening. The third patient is a female, who developed encephalopathy, and paroxysmal periods of lethargy alternated with irritability at 3 months of age. Diagnosis remained elusive even after consulting multiple doctors. A genetic test was finally performed at 7 months of age, and 2 pathogenic missense variants were identified in the TH gene: c.943G>A [p.(Gly315Ser)]; c.1196C>T [p.(Thr399Met)]. Treatment was started at a very low dose and gradually increased to the maximum effective dose of levodopa. During follow-up session, all of them showed significant motor recovery. The first patient, who is currently 9 years old, was able to ambulate with assistance. In addition, both the second patient (7 years of age) and the third patient (28 months of age) were able to walk independently. Hence, we concluded that TH deficiency is a treatable disorder if recognized early and should be considered in children with unexplained neurological symptoms.
KEYWORDS: M protein, Multiple myeloma. Immunofixation, Protein electrophoresis, younger age
