Two Rare Cases of Long Surviving Riboflavin Transporter Deficiency with Co-Existing Adenosine Monophosphate Deaminase (AMP) Deficiency

Research output: Contribution to journalArticleOtherpeer-review

1 Citation (Scopus)


(1) Background: Riboflavin transporter deficiency (RTD), formerly known as Brown–Vialetto–Van Laere syndrome, is a rare condition that causes a progressive neurological syndrome in early life with features of auditory and optic neuropathy, weakness of bulbar muscles and the diaphragm and sensorimotor neuropathy. Pathologic mutations in the genes that code for riboflavin transporters have been identified as the genetic basis of RTD, and the majority of the genetically confirmed cases are caused by mutations of SLC52A3, a riboflavin transporter 2 coding gene or compound mutations in SLC52A2, encoding riboflavin transporter 3. Fatality in childhood is common if the condition is left untreated, but survival into adulthood has been reported in cases treated with high-dose oral riboflavin. (2) Case summary: We report two long-term survivors of RTD type 2 due to compound heterozygous 185T> G and 1258G>A mutations in gene SLC2A2. They are two brothers in a family in which two female siblings died in childhood from a similar neurological disorder. Brother one, the older RTD survivor, is aged 71, and brother two is aged 58. Both have significant visual impairment from optic nerve atrophy and sensory ataxia. Their muscle biopsies showed decreased muscle adenosine monophosphate (AMP) deaminase activity. No AMPD1 mutation was detected through whole-genome sequencing. (3) Conclusion: Co-existing riboflavin transporter deficiency (RTD) type 2 and muscle AMP deaminase deficiency has not been previously reported. Apart from the possibility that there is a milder phenotype associated with these mutations in SLC2A2, AMP deaminase deficiency might have contributed to a survival benefit by preserving muscle function through accumulating intracellular AMP.

Original languageEnglish
Article number1605
Number of pages5
JournalBrain Sciences
Issue number12
Publication statusPublished - Dec 2022


  • adenosine monophosphate deaminase
  • AMPD1 mutation
  • riboflavin transporter deficiency

Cite this