A case of treatable encephalopathy, developmental regression, and proximal tremor: Expert commentary

Abstract

Dr Hull and colleagues report an instructive case of a male infant diagnosed with tyrosine hydroxylase deficiency (THD), who showed clinical benefit with levodopa therapy [ [1] Hull M. Emrick L. Sadat R. Parnes M. A case of treatable encephalopathy, developmental regression, and proximal tremor. Park. Relat. Disord. 2021; https://doi.org/10.1016/j.parkreldis.2021.04.020 Abstract Full Text Full Text PDF Scopus (1) Google Scholar ]. THD is a recessive monoamine synthesis disorder associated with loss-of-function mutations in the gene encoding the enzyme that converts tyrosine to l-dopa for subsequent dopamine synthesis; together with GCH1-related disease and sepiapterin reductase deficiency, THD is considered to be one of the dopa-responsive neurotransmitter disorders. Although THD has previously been clinically classified into Type A and B subtypes [ [2] Willemsen M.A. Verbeek M.M. Kamsteeg E.J. de Rijk-van Andel J.F. Aeby A. Blau N. Burlina A. Donati M.A. Geurtz B. Grattan-Smith P.J. Haeussler M. Hoffmann G.F. Jung H. de Klerk J.B. van der Knaap M.S. Kok F. Leuzzi V. de Lonlay P. Megarbane A. Monaghan H. Renier W.O. Rondot P. Ryan M.M. Seeger J. Smeitink J.A. Steenbergen-Spanjers G.C. Wassmer E. Weschke B. Wijburg F.A. Wilcken B. Zafeiriou D.I. Wevers R.A. Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis. Brain. 2010; 133: 1810-1822 Crossref PubMed Scopus (142) Google Scholar ], it is increasingly evident that the condition encompasses more of a phenotypic continuum, from severe neonatal encephalopathy to infantile/childhood-onset motor and cognitive delay with parkinsonism-dystonia, oculogyric crises and autonomic features. This infant clearly displays some of these core disease features, including tremor, paucity of spontaneous movement, and clear response to dopaminergic treatment.