P.387 - Riboflavin transporter deficiency diagnosed 30 years after onset of symptoms

Abstract

Mutations in the riboflavin transporter genes SLC52A2 and SLC52A3 cause a neurodegenerative disorder formerly known as Brown–Vialetto–van Laere (BVVL) syndrome, now renamed to riboflavin transporter deficiency. We present a patient who developed hypotonia, respiratory problems and feeding problems at the age of 8 months. His respiratory problems necessitated mechanical ventilation for 8 months. During follow up global developmental delay, bilateral sensorineural deafness and profound sensory ataxia were diagnosed. Extensive additional investigations (MRI, EMG, metabolic workup, CSF analysis and muscle biopsy) in infancy did not reveal any abnormalities apart from raised ethylmalonic acid. As a mitochondrial disorder was suspected he was treated with thiamine, riboflavin, biotin and carnitine. In the ensuing years these supplements were discontinued twice. Each time parents noticed worsening of his clinical condition. A second muscle biopsy performed at the age of 15 years showed central cores. Sequencing of RYR1 gene revealed one missense mutation, which was also present in the asymptomatic mother. Whole exome sequencing performed at the age of 30 years revealed a homozygous mutation in SLC52A3 gene (c.1128C > G(p.(Tyr376*)), which led to the diagnosis of Brown–Vialetto–van Laere syndrome. Riboflavin transporter deficiencies formerly known as Brown–Vialetto–van Laere syndrome present with cranial nerve deficits including hearing loss, weakness, sensory symptoms including sensory ataxia, feeding difficulties and respiratory difficulties which are caused by a progressive axonal sensory and motor peripheral neuropathy and a cranial neuropathy. Diagnosis can only be made through molecular analysis of all genes. Treatment with oral supplementation of riboflavin is lifesaving.