Three cases of adult-onset Brown-Vialetto-Van Laere syndrome: Novel variants in SLC52A3 gene and MRI abnormalities

Carey, Guillaume; Kuchcinski, Grégory; Gauvrit, F.; Defebvre, Luc; Nguyen, Sylvie; Dhaenens, Claire‐Marie; Dessein, Anne Frédérique; Vianey‐Saban, Christine; Acquaviva, Cécile; Tard, Céline

doi:10.1016/j.nmd.2021.06.009

Cited by 8 publications

(6 citation statements)

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“…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.…”

Section: Resultsmentioning

confidence: 99%

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

Fennessy

Cornett

Burns

et al. 2023

J Peripheral Nervous Sys

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Background and AimsRiboflavin Transporter Deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised by pontobulbar palsy, sensorineural deafness, sensory ataxia, muscle weakness, optic atrophy and respiratory failure. Riboflavin supplementation has been shown to be beneficial in short‐term reports but the quantum of benefit in various clinical domains is not well understood.MethodsA PubMed search was conducted which identified 94 genetically confirmed cases of RTD who received riboflavin supplementation and had follow‐up assessments. Information on the clinical and functional status before and after riboflavin supplementation was collected and analysed.ResultsSeventy‐six of the 94 patients (80.9%) showed an overall improvement after riboflavin supplementation, and the remaining (19.1%) were stable, though some patients had deteriorations in individual domains with no reported deaths. The domains that had the highest rates of response to riboflavin supplementation were gross motor function (93.3% improved), bulbar palsy (91.3%), and ataxia (90.0%). Improvements were also seen in limb muscle weakness, audiology, facial nerve palsy and respiratory function. Despite treatment, many patients required assistance to ambulate and had severe or profound hearing loss and some remained gastrostomy or tracheostomy‐dependent.InterpretationRiboflavin supplementation is a life‐saving intervention for patients with RTD and results in profound improvement in several functional domains, with early diagnosis and treatment further improving outcomes. Despite treatment, patients are left with residual disability. There is a need to accurately measure functional outcomes in children with RTD and develop additional disease modifying therapies.This article is protected by copyright. All rights reserved.

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Section: Resultsmentioning

confidence: 99%

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

Fennessy

Cornett

Burns

et al. 2023

J Peripheral Nervous Sys

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“…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. This mutation was previously reported by Bashford et al (2016) in a patient with symptom onset at age 35, with bulbar and motor symptoms and dramatic response to riboflavin replacement.…”

Section: Discussionmentioning

confidence: 99%

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

Marques,

Santos,

Fidalski

et al. 2024

Journal of Pediatric Neurology

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Brown–Vialetto–Van Laere syndrome or riboflavin transporter deficiency is a rare and genetically determined condition that results in a spectrum of neurological signs and symptoms from generalized muscle weakness to cranial nerve involvement with medullary symptoms and respiratory failure. Most patients have SLC52A3 gene biallelic variants, but some of them may have impairment of SLC52A2 gene, both related to the cell transport of riboflavin. We report the case of three unrelated Brazilian patients under 18 years of age with this diagnosis confirmed by molecular genetic sequencing. We observed that the clinical manifestations found were compatible with those already described in the literature by age group. Unusual findings of retinitis pigmentosa and immunodeficiency were identified related to pathogenic variants in the SLC52A2 gene. All patients received riboflavin replacement at a therapeutic dose without gastrointestinal intolerance and with clinical improvement after starting treatment.

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“…There was a marked improvement in audiometric tests, from 80 dB at 8 kHz before riboflavin therapy to 40–55 dB at 8 kHz afterwards [ 3 ]. Recently, Carey and colleagues reported hearing improvement in 3 cases after long-term (3–6 months) treatment with riboflavin (1–1.5 g/d), use of hearing aids, and speech therapy [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

A Case Report of Riboflavin Treatment and Cochlear Implants in a 4-Year-Old Girl with Progressive Hearing Loss and Delayed Speech Development: Brown-Vialetto-Van Laere Syndrome

Piecuch,

Skarżyński,

Skarżyński

2023

Am J Case Rep

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Patient: Female, 4-year-old Final Diagnosis: Brown-Vialetto-Van Laere syndrome Symptoms: Hearing loss auditory neuropathy • delayed speech development • pontobulbar palsy Clinical Procedure: Bilateral cochlear implantation Specialty: Otolaryngology Objective: Rare disease Background: Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a motor neuron disorder of childhood, which can be associated with sensorineural deafness. This report describes a 4-year-old Polish girl with progressive hearing loss and delayed speech development diagnosed with Brown-Vialetto-Van Laere syndrome who was treated with riboflavin (vitamin B2) and cochlear implants. Case Report: The case report concerns a girl from Poland who, at the age of 2 years 10 months, developed progressive atypical neurological symptoms of unknown etiology: ataxia of the upper and lower limbs, gait abnormalities, generalized muscle weakness, visual and hearing problems, and regression of speech development. A karyotype study (whole-exome sequencing) revealed alterations within SLC52A2, leading to the diagnosis of Brown-Vialetto-Van Laere syndrome and initiation of high-dose riboflavin treatment. As a 4-year-old child, she presented to the Institute of Physiology and Pathology of Hearing – World Hearing Center in Poland with progressive hearing loss and speech regression. Hearing tests revealed bilateral profound sensorineural hearing loss with auditory neuropathy. Surgical treatment was applied in the form of bilateral cochlear implantation. Conclusions: This report shows the importance of genetic testing in infants who present with atypical symptoms or signs. In this case, the diagnosis of Brown-Vialetto-Van Laere syndrome resulted in timely correction of the genetic riboflavin (vitamin B2) deficiency and improved hearing following the use of cochlear implants.

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Three cases of adult-onset Brown-Vialetto-Van Laere syndrome: Novel variants in SLC52A3 gene and MRI abnormalities

Cited by 8 publications

References 8 publications

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

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

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

A Case Report of Riboflavin Treatment and Cochlear Implants in a 4-Year-Old Girl with Progressive Hearing Loss and Delayed Speech Development: Brown-Vialetto-Van Laere Syndrome

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