Brown-Vialetto-Van laere syndrome
At a minimum, these SNPs are known to be related, and others may also be
BVVL is a rare, progressive, neurodegenerative motor neuron disorder that specifically includes palsies (paralysis) of the cranial nerves. In 2010, the first gene for BVVL was discovered, elucidating the disease as a possible riboflavin transporter gene mutation. Since then, other genes have been discovered with similar malfunction. There are over 70 known cases of BVVL, based on recessively inherited mutations in either the SLC52A2 or SLC52A3 genes, leading to either BVVL type 2 or type 1, respectively.
Symptoms vary from infancy to the third decade. In many cases, children lead a normal life developmentally, disease-free, for years before developing symptoms. Typically, the first symptom is sensorineural deafness. Other examples of nerve degeneration include vocal cord paralysis, ptosis (droopy eyelids), facial weakness, slurred speech, dysphagia (difficulty swallowing), visual difficulty secondary to optic atrophy, neck and shoulder weakness, limb weakness, autonomic dysfunction, and respiratory compromise.
A 2016 publication summarizing the first 5 years of oral supplementation with riboflavin concludes that this treatment is lifesaving for both types of BVVL. Therefore, if a riboflavin transporter deficiency is suspected, treatment must be started immediately without first awaiting the results of molecular diagnostics.[PMID 26973221]
Brown-Vialetto-Van Laere syndrome-1 (BVVLS1) is caused by homozygous or compound heterozygous mutation in the SLC52A3 (also known as C20Orf54) gene on chromosome 20. Mutations in the SLC52A3 gene also result in Fazio-Londe disease, a disorder similar to BVVLS but without sensorineural deafness.