To Be or No B2: A Rare Cause of Stridor and Weakness in a Toddler

Abstract

We present a case of a young child with a rare metabolic disorder whose clinical presentation resembled that of autoimmune myasthenia gravis. The differential diagnosis was expanded when autoantibody testing was negative and the patient did not respond to standard immunomodulatory therapies. Rapid whole genome sequencing identified 2 rare variants of uncertain significance in the SLC52A3 gene shown to be in compound heterozygous state after parental testing. Biallelic mutations in SLC52A3 are associated with Riboflavin Transporter Deficiency, which in its untreated form, results in progressive neurodegeneration and death. Supplementation with oral riboflavin has been shown to limit disease progression and improve symptoms in some patients. When the diagnosis is suspected, patients should be started on supplementation immediately while awaiting results from genetic studies.

Benefit of high‐dose oral riboflavin therapy in riboflavin transporter deficiency

“…A summary of the articles that reported follow‐up data in each of the domains is shown in Table S1. Forty‐seven of those patients had RTD2 due to biallelic mutations in SLC52A2 , 2–4,12,14–33 46 had RTD3 due to biallelic mutations in SLC52A3 18,20,24,27,31,34–57 and one patient had a mutation in both SLC52A2 and SLC52A3 58 . Seventy‐six of the 94 patients (80.9%) showed an overall improvement after riboflavin supplementation, and the remaining (19.1%) were stable after riboflavin supplementation.…”

Phenotypic Variability Related to Mutations in Riboflavin Transporter in Brazilian Children: Pediatric Case Series

“…[33][34][35][36] Nonsense mutations in the SLC52A3 gene have been reported in patients with severe conditions, often with fatal evolution in a short time, and with an early onset. 37,38 Missense variants can lead to different clinical presentations, with manifestations occurring in both early and late onset. 10,39,40 The D461Y variant represents a mutation in exon 5 of the SLC52A3 gene, encoding an amino acid positioned at the end of the protein (at position 461 out of 470), situated in the last topological domain of RFVT3.…”