Delineating the phenotypic spectrum of sulfite oxidase and molybdenum cofactor deficiency
Albert Misko, Ye Liang, Joshua B. Kohl, Florian Eichler
Abstract
OBJECTIVE: To define the phenotypic spectrum of isolated sulfite oxidase (ISOD) and molybdenum cofactor deficiency (MoCD), aiming to promote timely diagnosis and assist in future clinical trial design. METHODS: We analyzed clinical, radiographic, biochemical, and genetic data from 146 patients reported in the literature. RESULTS: We stratified patients into 2 phenotypic subgroups based on clinical and radiographic characteristics. In the first (Class I), patients presented early in life (age 1-50 days) with acute onset of neurologic symptoms and development of diffuse brain injury with cystic leukomalacia. Patients in the second subgroup (Class II) presented later in life (age 30 days-23 years) with prominent movement abnormalities and selective injury of the basal ganglia and cerebellum. A significant difference in survival estimates correlated with milder disease severity among Class II patients. Substantial overlap in sulfur-containing metabolite levels prevented discrimination of subgroups based on diagnostic biomarkers, but genotype-phenotype correlations suggested that residual SUOX activity may contribute to milder phenotypes. CONCLUSIONS: Patients with SUOX and MoCD gravitate toward 1 of 2 distinct clinicoradiographic profiles. Patient stratification may help promote accurate diagnosis, prognostication, and aid in the design of future clinical trials.