Riboflavin Transport Deficiency

Baby Detect > Metabology > Riboflavin Transport Deficiency

SLC52A2 and SLC52A3 gene

Also known as: Brown-Vialetto-Van Laere syndrome 1; Brown-Vialetto-Van Laere syndrome 2; Riboflavin transporter deficiency 2 (RFVT2); Riboflavin transporter deficiency 3 (RFVT3); bulbar palsy, progressive, with sensorineural deafness or pontobulbar palsy with deafness.

OMIM#211530 https://omim.org/entry/211530

OMIM#614707 https://omim.org/entry/614707

1. The disease:

Rare genetic motor neuron disease characterized by a peripheral and cranial neuropathy, neuronal loss in anterior horns and atrophy of spinal sensory tracts, causing muscle weakness, sensory loss, diaphragmatic paralysis and respiratory insufficiency, and multiple cranial nerve deficits such as sensorineural hearing loss, bulbar symptoms, and loss of vision due to optic atrophy. This group of genes causes defects in the transporter of vitamin B2 (riboflavin). Riboflavin transporter results in cellular flavin deficiency in different tissues. As flavins play an important role in mitochondrial function, mitochondrial dysfunction might act as a pathomechanism contributing to neurodegeneration in Riboflavin Transport deficiency. Depending on the transporter affected, Riboflavin transporter deficiency 2 (RFVT2) and Riboflavin transporter deficiency 3 (RFVT3) are distinguished.

2. The symptoms :

it can occur like a clinical spectrum from early infancy until adulthood, with a more severe presentation at a younger age. The most frequent presenting symptoms are cranial neuropathy, sensory ataxia, muscle weakness and respiratory insufficiency due to diaphragmatic paralysis. The cranial neuropathy leads to sensorineural hearing loss, loss of vision due to optic atrophy, dysarthria, dysphagia, feeding problems, facial weakness and eye movement impairments. Diaphragmatic paralysis in combination with general muscle weakness may rapidly lead to respiratory insufficiency, especially in infants and young children. Often, feeding through a nasogastric tube or gastrostomy device and artificial ventilation and tracheotomy are required. Sensory ataxia and optic atrophy seem more prevalent in RFVT2 than RFVT3 deficient patients. Lack of early signs or symptoms does not exclude the diagnosis.

3. Actions to take in case of early diagnosis

  • Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in one of these genes) should continue breastfeeding. Early treatment is essential in preventing chronic symptoms.
  • Biochemical correlation is essential for confirming diagnosis. Biochemical tests can show abnormalities such as abnormal (MADD-like) plasma acylcarnitine profiles, abnormal urine organic acids and decreased plasma flavin levels; however, approximately 50% of patients have normal results. In case of normal results, the follow-up in the metabolic clinic is essential.
  • RFVT is a lifelong disease that requires lifetime management and regular follow-up with a metabolic physician and a multidisciplinary approach to care.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information