PROCEEDINGS OF THE XIX CONGRESS OF THE ITALIAN SOCIETY OFMYOLOGY

摘要

GMPPB, encoding the guanosine-diphosphate-mannose (GDP-mannose) pyrophosphorylase B protein, has recently been associated with a wide clinical spectrum ranging from severe Walker-Warburg syndrome to pseudo-metabolic myopathy and even congenital myasthenic syndromes.In our previous research, we identified 13 additional cases from 12 families and defined seven novel mutations.In line with data from the literature, patients displayed variable phenotypes and mutations in GMPPB are more common in relatively milder forms of neuromuscular disorders.However, what our study adds to this already broad clinical spectrum is the possible presence of arthrogryposis and congenital clubfoot, particularly in patients with very severe, generalized involvement, as well as nystagmus and upgaze palsy. Ataxia could be part of the clinical picture, in line with possible evidence of cerebellar atrophy. Intellectual disability was evident in all the congenital forms, predominantly affecting the language domain.The onset of motor manifestations in the LGMD group occurred at different ages and the extent of weakness was unrelated to the timing of onset of the disease. Less severe phenotypes are also observed, such as exercise intolerance and myoglobinuria or easy fatigability or asymptomatic hyperCKemia with subtle weakness, evident only on expert clinicalexamination.We also demonstrated that few mutations recur in the ItalianGMPPB-mutated population.Our findings, combined with literature data, show that there are at leastthree forms of GMPPB-related myopathy: i) CMD, ii) earlyonset LGMD, and iii) adult onset LGMD, often with evidence of neuromuscularjunction involvement.