Five-year update on siblings with riboflavin transporter deficiency

O'Brien MA, Culican SM, Shinawi MS, Zaidman CM. Child Neurology: Five-Year Update on Siblings With Riboflavin Transporter Deficiency: Stable Visual and Neurologic Status With Continued Riboflavin Therapy. Neurology. 2024 Dec 10;103(11):e209969. doi: 10.1212/WNL.0000000000209969. Epub 2024 Nov 15. PMID: 39546739.

Abstract

Riboflavin transporter deficiency (RTD), previously referred to as Brown-Vialetto-Van Laere syndrome, is caused by pathogenic variants in the SLC52A1, SLC52A2, or SLC52A3 genes, resulting in RTD types 1, 2, and 3, respectively. Researchers estimate an occurrence of approximately 1 in 1,000,000. There is only one case of type 1 described in medical literature. Type 2 is characterized by muscle weakness in the arms and neck, vision loss, hearing impairment, and sensory ataxia. In type 3, vocal cord paralysis is more common and muscle weakness is more generalized. In 2018, we described a case of a 6-year-old girl with RTD type 2 who made remarkable visual recovery after initiation of treatment with oral riboflavin and coenzyme Q10 supplementation. The patient's younger brother began the same treatment regimen after genetic testing confirmed that he carried the same genetic variant. In this report, we update the visual and neurologic status in these siblings 5 years after our initial report and 7.5 years after initiation of riboflavin treatment.

Excerpt

This report provides long-term follow-up (>7 years) on visual and neurologic status after riboflavin supplementation in 2 patients with RTD. OCT imaging illustrates irreversible damage to the nonmyelinated axons of retinal ganglion cells, apparent as severe but stable RNFL thinning and corresponding 360 degrees of peripheral visual field constriction. The optic nerve, on the contrary, consists of heavily myelinated axons. We hypothesize that reintroduction of riboflavin allows coenzymes FAD and FMN to enhance availability of intracellular ATP and mitochondrial survival. This is followed by an increase in myelin production along the optic nerve, restoring fibers that allow for return to 20/20 visual acuity.
Starting riboflavin treatment as soon as RTD is suspected is recommended to minimize the risk of permanent neurological and visual damage. Given the safety of riboflavin, supplementation may be given to patients (and siblings) with suspicion of RTD while waiting for results of genetic testing. Until more long-term research or a cure is available, patients must continue lifelong riboflavin supplementation.