A case report of riboflavin transporter deficiency: A novel heterozygous pathogenic variant in the SLC52A3 gene.

Riboflavin transporter deficiency (RTD) is a neurodegenerative disorder that presents from infancy to adulthood with a progressive axonal neuropathy characterized by a variety of neurologic symptoms including hearing loss, weakness, bulbar palsy, and respiratory insufficiency. Pathogenic variants in SLC52A2 and SLC52A3 are implicated in the pathogenesis of RTD type 2 and 3, respectively. Early identification of this disorder is critical, as it is treatable with riboflavin supplementation. We describe a 16-year-old female with a phenotype consistent with RTD3 found to have a novel heterozygous SLC52A3 variant. Though RTD is typically considered an autosomal recessive condition, her heterozygous variant was thought to be disease causing after further genetic analysis and given her improvement in response to riboflavin supplementation. This case highlights the importance of reinterpretation of genetic testing, particularly when there is a high clinical suspicion for disease.

Brown-Vialetto-Van Laere syndrome and Fazio-Londe syndrome: A novel mutation and in silico analyses.

Brown-Vialetto-Van Laere syndrome, a rare neurological disorder is due to SLC52A3 mutations. Here, the SLC52A3 protein and its mutations are in silico structurally and functionally analyzed among all the reported patients and a novel mutation is also reported. After clinical evaluations, SLC52A3 gene was sequenced and segregation analysis of the mutations was also checked. A comprehensive search was performed on the reported mutations of SLC52A3 gene. In silico structural and functional analyses of the mutations and interactome analyses of the protein were done using available software tools. Mutations of 37 affected individuals were identified. Thirty three mutations were determined. c.502A > C was a novel variant that it was segregated within the family. One mutation (c.639C > G) was responsible for 12% of the mutations. Segregation analysis, secondary structure, functional prediction achieved for the novel mutation showed pathogenicity of this variant. BVVL is a very rare disorder; SLC52A3 mutations are distributed among different populations and there might be one frequent mutation in this gene. BVVL should be more considered in Iran. In addition to segregation analysis, computational analyses could accelerate understanding the extent of pathogenicity of the novel variants.

Fazio-Londe syndrome in siblings from India with different phenotypes.

BACKGROUND: Fazio-Londe syndrome also called progressive bulbar palsy of childhood is a very rare motor neuron disease of pediatric age group characterized by progressive paralysis of lower cranial nerves. OBJECTIVE: To describe Fazio-Londe syndrome in sibling with different phenotype. METHODS: A 6 years old female child presented with inability to close eyes, difficulty in swallowing, respiratory muscle weakness and voice change since 5 yr of age. Examination showed lower motor neuron facial nerve palsy, absent gag reflex, tongue atrophy, fasciculation, limb wasting and exaggerated deep tendon reflexes. An 11 year old boy, elder sibling of the above child presented with similar complaints at 10 years of age, other than later onset and lack of respiratory problem. Genetic testing in both cases confirmed the diagnosis of Fazio-Londe Syndrome. CONCLUSION: In any child who presents with progressive bulbar palsy with lower motor neuron facial palsy a diagnosis of Fazio-Londe Syndrome should be considered and family members should also be screened.

Riboflavin Treatment in Genetically Proven Brown-Vialetto-Van Laere Syndrome.

Brown-Vialetto-Van Laere (BVVL) syndrome is a rare motor neuron disorder of childhood, which forms a continuous spectrum with Fazio-Londe syndrome. It is an autosomal-recessive inherited disease caused by mutations in intestinal riboflavin transporter genes. We describe a child with genetically proven BVVL syndrome where prompt treatment with riboflavin showed good results.

Brown-Vialetto-Van Laere Syndrome as a Mimic of Neuroimmune Disorders: 3 Cases From the Clinic and Review of the Literature.

We present 3 patients identified at 2 different institutions with Brown-Vialetto-Van Laere syndrome. Each patient was initially diagnosed with a neuroimmune disorder for a period of a few weeks to a few months. In each case, genetic analysis revealed mutations in one of the riboflavin transporters, confirming Brown-Vialetto-Van Laere syndrome. It is likely that Brown-Vialetto-Van Laere syndrome is more common than previously reported, and because it mimics neuroimmune disorders, it may be misdiagnosed as such. It shares many features with diseases such as chronic inflammatory demyelinating neuropathy, may present with positive cerebrospinal fluid antibody titers, and may transiently respond to intravenous immunoglobulin. We review the literature on Brown-Vialetto-Van Laere syndrome and Fazio-Londe syndrome, 2 riboflavin transporter disorders, looking for clinical presentations that may lead to confusion with neuroimmune disorders. We emphasize the importance of correctly diagnosing the disease, as its treatment is relatively benign and will stop progression of the disease and may even reverse it.