Dataset Information

Successful treatment of a genetic childhood ataxia due to riboflavin transporter deficiency.

ABSTRACT:

Background

Riboflavin transporter deficiency (Brown-Vialetto-Van Laere syndrome) is a rare recessive neurodegenerative disorder that can present with gait ataxia, primarily due to sensory neuropathy as well as cerebellar involvement. Although sensorineural hearing loss, bulbar palsy, and optic atrophy are typical, presentation may be variable and an atypical condition may be difficult to recognize clinically.

Case presentation

Here we report a patient presenting at age 8 with progressive ataxia since the age of 2.5 years with cerebellar atrophy and peripheral polyneuropathy. Whole exome sequencing identified a known pathogenic mutation in the SLC52A2 gene consistent with a diagnosis of Brown-Vialetto-Van Laere syndrome despite the absence of common symptoms including motor neuropathy, bulbar palsy, optic atrophy, and sensorineural hearing loss. High-dose riboflavin therapy was initiated, symptoms stabilized, metabolic abnormalities resolved, and the patient is doing well with a near-normal examination at age 15.

Conclusions

Riboflavin transporter deficiency can be fatal if left untreated. The excellent outcome of this case illustrates the importance of identifying this potentially treatable neurologic condition. In this patient, clinical diagnosis was limited by an atypical presentation lacking several common features which was overcome through the use of genomic sequencing identifying the pathogenic mutation enabling correct diagnosis and subsequent treatment. Riboflavin transporter deficiency should be considered early in the diagnostic evaluation as a treatable form of ataxia in children, even if patients lack typical features.

SUBMITTER: Fan J

PROVIDER: S-EPMC6196015 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Successful treatment of a genetic childhood ataxia due to riboflavin transporter deficiency.

Fan Judy J Fogel Brent L BL

Cerebellum & ataxias 20181020

<h4>Background</h4>Riboflavin transporter deficiency (Brown-Vialetto-Van Laere syndrome) is a rare recessive neurodegenerative disorder that can present with gait ataxia, primarily due to sensory neuropathy as well as cerebellar involvement. Although sensorineural hearing loss, bulbar palsy, and optic atrophy are typical, presentation may be variable and an atypical condition may be difficult to recognize clinically.<h4>Case presentation</h4>Here we report a patient presenting at age 8 with prog ...[more]

PMID: 30377535

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Project description:Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms.

Dataset Information

Successful treatment of a genetic childhood ataxia due to riboflavin transporter deficiency.

Background

Case presentation

Conclusions

Publications

Successful treatment of a genetic childhood ataxia due to riboflavin transporter deficiency.

Similar Datasets

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