Neuropathy transporter deficiency Riboflavin (Riboflavin transporter deficiency neuronopathy) - Genes SLC52A2 or SLC52A3
Neuropathy riboflavin transporter deficiency is a process that affects neurons. People usually have sensorineural hearing loss and other signs of damage to auditory nerves. In addition to the nerves in the inner ear disease it affects the nerves found in the brainstem, specifically in the pontobulbar region. Damage to these nerves causes paralysis pontobulbar. The nerves in the region pontobulbar help control voluntary muscle several activities, including breathing, speech and limb movement. Pontobulbar as a result of paralysis, affected individuals may exhibit respiratory problems, slurred speech and muscle weakness of the face, neck, shoulders and limbs. Affected individuals may also have spasticity and exaggerated reflexes.
The age of onset of neuropathy transporter deficiency of riboflavin can vary from infancy to adulthood. When the disease manifests in infancy, the early symptoms usually include respiratory problems due to nerve damage, which can be potentially fatal. When the disease begins in children or young adults, sensorineural hearing loss usually occurs first, followed by pontobulbar signs of paralysis. If left untreated, the signs and symptoms of neuropathy transporter deficiency of riboflavin worsen over time. Severe breathing problems and respiratory infections are the most common cause of death in people with this disease. Without treatment, affected children usually survive less than one year. However, people who develop the disease after age 4, usually survive more than 10 years.
Neuropathy transporter deficiency of riboflavin encompasses two entities previously considered distinct: syndrome Brown-Vialetto-Van Laere (BVVLS) and Fazio-Londe disease. Both entities have similar signs and symptoms, but the disease Fazio-Londe not include sensorineural hearing loss. Because these two diseases share a genetic cause and have features that overlap, it has been proposed that are forms of the same disease.
This may be due to mutations in the SLC52A2 gene (solute carrier family 52 member 2), located on the long arm of chromosome 8 (8q24.3) or SLC52A3 (solute carrier family 52 member 3) gene, located in the short arm of chromosome 20 (20p13). These genes encode transporters riboflavin 2 (RFVT2) and 3 (RFVT3), respectively. Both proteins transported riboflavin (also called vitamin B2) through the cell membrane. The RFVT3 protein is found in especially high concentrations in the small intestine cells and is important for the absorption of riboflavin during digestion so that vitamin can be metabolized in the body. The RFVT2 protein is found in brain cells and spinal cord and is important to ensure that these tissues have enough riboflavin for proper operation. In body cells, riboflavin is the main component adenine dinucleotide molecules flavin (FAD) and flavin mononucleotide (FMN). FAD and FMN are involved in many different chemical reactions and are needed for a variety of cellular processes. An important function of these molecules in cellular energy production. FAD and FMN are also involved in the breakdown of carbohydrates, fats and proteins.
They have been described at least 11 SLC52A2 gene mutations and 24 mutations in the SLC52A3 gene in people with neuropathy transporter deficiency of riboflavin. Mutations in the SLC52A3 gene SLC52A2 or inhibit protein synthesis or give rise to a carrier protein abnormal riboflavin with impaired ability to transport riboflavin. Consequently, a decrease in the amount of riboflavin available is produced in the body. It is unclear how these changes lead to nerve problems characteristic of the disease.
Neuropathy riboflavin transporter deficiency usually follows an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with neuropathy transporter deficiency riboflavin, by complete PCR amplification of exons SLC52A2 and SLC52A3 of, respectively, and subsequent sequencing genes.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).