Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes: a clinical, biochemical and genetic study

Neuromuscul Disord. 2012 Dec;22(12):1075-82. doi: 10.1016/j.nmd.2012.05.007. Epub 2012 Jul 21.

Abstract

Brown-Vialetto-van Laere (BVVL) and Fazio-Londe (FL) are rare and clinically overlapping motor neurons syndromes. Recently BVVL has been associated with mutations in C20orf54/hRFT2 and defective riboflavin transport. We compared clinical and laboratory features of 6 patients (age range 11-17 years), with features of BVVL and FL overlap syndromes. Patients were assessed as following: blood levels of riboflavin and redox status, electrophysiological, neuroradiological and pulmonary studies, ALS functional rating scale and molecular genetic analysis. Two patients manifested deafness at ages of 3 and 10 years, and developed later subacute progressive ponto-bulbar palsy. A third patient markedly improved after intravenous immunoglobulins (IVIG), but then relapsed remaining unresponsive to treatment; he was not deaf although had abnormal auditory evoked responses (BAERs). The remaining 3 patients had no deafness, although likewise manifested subacute progressive ponto-bulbar palsy. We found hRFT2 mutations in 3/6 patients manifesting deafness or abnormal BAERs. No patient had reduced riboflavin blood levels. However, on riboflavin supplementation (10mg/kg/day) the most severely affected BVVL patient stopped progression of symptoms following 8 months of treatment. BVVL and FL are severe progressive diseases with overlapping symptoms although only hRFT2 mutated patients manifest deafness. Riboflavin supplementation seems to stabilize and improve progression of the disease.

MeSH terms

  • Adolescent
  • Bulbar Palsy, Progressive / complications
  • Bulbar Palsy, Progressive / diagnosis
  • Bulbar Palsy, Progressive / drug therapy
  • Bulbar Palsy, Progressive / genetics*
  • Child
  • Child, Preschool
  • Deafness / complications
  • Deafness / genetics
  • Disease Progression
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Evoked Potentials, Auditory, Brain Stem / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Hearing Loss, Sensorineural / complications
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / drug therapy
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Motor Neurons / drug effects
  • Motor Neurons / pathology
  • Mutation / genetics
  • Riboflavin / blood
  • Riboflavin / therapeutic use
  • Treatment Outcome

Substances

  • Riboflavin

Supplementary concepts

  • Brown-Vialetto-Van Laere syndrome