What is RTD – Riboflavin Transporter Deficiency ?
RTD is a disorder characterized by nerve problems, particularly hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss). The age at which this condition begins varies from infancy to young adulthood. When RTDbegins in infancy, the first symptom is often breathing problems caused by nerve damage. When the condition begins in children or young adults, sensorineural hearing loss usually occurs first, followed by signs of other nerve problems.
RTD involves nerves found in the part of the brain that is connected to the spinal cord (the brainstem). In particular, certain nerves that are found in a region of the brainstem known as the pontobulbar region are damaged in people with this condition, causing paralysis of muscles controlled by the affected nerves. This abnormality is called pontobulbar palsy. Nerves in this region help control voluntary muscle activities such as walking, speaking, and some aspects of breathing. As a result of pontobulbar palsy, people with RTD can have breathing problems; slurred speech; and muscle weakness in the face, neck, shoulders, and limbs. Affected individuals can also have muscle stiffness (spasticity) and exaggerated reflexes.
The signs and symptoms of this condition worsen with age. Approximately one-third of affected individuals survive more than 10 years after the condition begins. Severe breathing problems and respiratory infections are often fatal in people with BVVLS. For unknown reasons, RTD occurs in approximately three times more females than males, but males seem to be more severely affected.
A condition called Fazio-Londe disease has similar signs and symptoms as RTD except without sensorineural hearing loss. It is unclear if Fazio-Londe disease and RTD are separate disorders or forms of the same condition.
How common is RTD?
RTD is a rare condition. Approximately 74 cases have been reported in the scientific literature
What genes are related to BVVLS?
RTDS is caused by mutations in the SLC52A1/SLC52A2/SLC52A3 genes (previously called the C20orf54 gene). These genes provides instructions for making the riboflavin transporter 1,2 & 3 (RFT1, RFT2, RFT3 )proteins, which transports a vitamin called riboflavin (or vitamin B2) across the cell membrane. Riboflavin cannot be made by the body, so it must be obtained from the food a person eats. The protein is found at especially high levels in cells of the small intestine and is important for absorbing riboflavin from the small intestine after digestion so that the vitamin can be used in the body.
Riboflavin is the core component of molecules called flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). These molecules function as coenzymes, which means they help enzymes carry out chemical reactions. FAD and FMN are involved in many different chemical reactions and are required for a variety of cellular processes. One important role of these coenzymes is in the production of energy for cells. FAD and FMN are also involved in the breakdown (metabolism) of carbohydrates, fats, and proteins.
Mutations in the SLC52A1/A2/A3 genes that cause RTD lead to an abnormal RFT1/2/3 proteins with impaired ability to transport riboflavin. Consequently, there is a reduction of riboflavin available in the body. However, it is unclear how these changes lead to the signs and symptoms of RTD
How do people inherit RTD ?
About half of all cases of RTD are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
The other half of RTD cases are not inherited and occur in people with no history of the condition in their family. These cases are described as sporadic.