title: Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes: a clinical, biochemical and genetic study.
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.
authors: Unit of Neuromuscular Disorders, Rehabilitation and Laboratory of Biochemistry, Bambino Gesu' Children's Research Hospital IRCCS, Rome, Italy.
authors: Marianna
authors: M
authors: Ciccolella
authors: Michela
authors: M
authors: Catteruccia
authors: Sabina
authors: S
authors: Benedetti
authors: Isabella
authors: I
authors: Moroni
authors: Graziella
authors: G
authors: Uziel
authors: Chiara
authors: C
authors: Pantaleoni
authors: Luisa
authors: L
authors: Chiapparini
authors: Alberto
authors: A
authors: Bizzi
authors: Adele
authors: A
authors: D'Amico
authors: Fabiana
authors: F
authors: Fattori
authors: Maria Letizia
authors: ML
authors: Salsano
authors: Anna
authors: A
authors: Pastore
authors: Giulia
authors: G
authors: Tozzi
authors: Fiorella
authors: F
authors: Piemonte
authors: Enrico
authors: E
authors: Bertini
mesh_terms: D000293:Adolescent; D010244:Bulbar Palsy, Progressive / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003638:Deafness / Q000150:complications / Q000235:genetics; D018450:Disease Progression; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D009154:Mutation / Q000235:genetics; D012256:Riboflavin / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D012256:Riboflavin