Nephrocalcinosis in genetically proved dopa-responsive dystonia due to sepiapterin reductase deficiency in a Libyan Girl

Abstract

Dopa-responsive dystonia (DRD) encompasses clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia and exhibit a robust and sustained response levodopa treatment. GCH1 gene mutations are the most frequent cause of DRD. Mutations in the TH or SPR gene less often cause this condition. The index case is a 12-year-old young girl presented to the pediatric neurology clinic at the age of 8 years with tiptoes walking and deterioration of her gait. She is the product of first-degree consanguineous marriage with insignificant history. The index case has two sisters, one of whom suffers from learning difficulties, epilepsy, and bilateral nephrocalcinosis. Her two uncles had severe axonal polyneuropathy and died in their forties of unknown cause. Her magnetic resonance imaging of the brain demonstrated agenesis of the corpus callosum. Renal ultrasound studies showed bilateral nephrocalcinosis. Genetic DNA evaluation (whole-exome sequencing) identified the heterozygous variant c.207C>G,p. (Asp69Glu) in the SPR gene (OMIM: 182125), which leads to an amino acid exchange. Nine out of ten bioinformatic in silica programs predict a pathogenic effect for this variant. Treatment with levodopa\ benserazide 4:1 (Madopar) has not made any changes to the girl's condition.