Clinical Guidance
Riboflavin transporter deficiency 2 (caused by biallelic SLC52A2 pathogenic variants) and riboflavin transporter deficiency 3 (caused by biallelic SLC52A3 pathogenic variants) are clinically characterized by motor neuropathy, sensory neuropathy, and cranial neuronopathy . Motor neuropathy manifests as proximal and distal limb weakness (often with severe distal wasting and breathing problems due to paralysis of the diaphragm), sensory neuropathy as gait ataxia, and cranial neuronopathy as optic atrophy, sensorineural hearing loss, and bulbar palsy. In contrast, RTD1 (possibly caused by biallelic SLC52A1 pathogenic variants), reported in a single case report, may manifest in infancy as generalized or focal tonic-clonic seizures, metabolic acidosis, and hyperammonemia, responsive to riboflavin supplementation . Riboflavin Deciency 2 and 3 While most individuals with RTD2 or RTD3 (caused by biallelic pathogenic variants in SLC52A2 or SLC52A3, respectively) present early in life, late onset (ages 10-30 years) has been reported in persons with RTD3. Males and females are equally affected. summarizes the frequency of select features in 136 individuals with molecularly confirmed RTD2 and RTD3. Table 2. Riboflavin Transporter Deficiency 2 and 3: Select Features Feature | % of Persons w/Feature
RTD2 (n=60) | RTD3 (n=76) | RTD2 RTD3 (n=136) |
|---|
Age of onset | Mean 3.2 yrs | Mean 8.5 yrs |
Peripheral neuropathy | 92% | 84% |
Motor neuropathy (weakness, hypotonia) | 77% | 80% |
Sensory neuropathy (gait abnormality, ataxia) | 60% | 13% |
Optic nerve atrophy/ ophthalmoplegia | 43% | 19% |
Facial weakness | 34% | 55% |
Hearing loss | 85% | 82% |
Bulbar palsy | 55% | 62% |
Respiratory involvement | 48% | 57% |
Feeding difficulties | 23% | 41% |
Abnormal cranial MRI | 19% (7/37) | 22% (13/60) |
Source: GeneReviews — "Riboflavin Transporter Deficiency"
