TY - JOUR
T1 - Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes
T2 - A clinical, biochemical and genetic study
AU - Ciccolella, Marianna
AU - Catteruccia, Michela
AU - Benedetti, Sabina
AU - Moroni, Isabella
AU - Uziel, Graziella
AU - Pantaleoni, Chiara
AU - Chiapparini, Luisa
AU - Bizzi, Alberto
AU - D'Amico, Adele
AU - Fattori, Fabiana
AU - Salsano, Maria Letizia
AU - Pastore, Anna
AU - Tozzi, Giulia
AU - Piemonte, Fiorella
AU - Bertini, Enrico
PY - 2012/12
Y1 - 2012/12
N2 - 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 (10 mg/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.
AB - 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 (10 mg/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.
UR - http://www.scopus.com/inward/record.url?scp=84870392607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870392607&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2012.05.007
DO - 10.1016/j.nmd.2012.05.007
M3 - Article
C2 - 22824638
AN - SCOPUS:84870392607
VL - 22
SP - 1075
EP - 1082
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
IS - 12
ER -