Gne Myopathy: Disease Progression In A Large Cohort Of Genetically Confirmed Cases From A Single Centre In India

Disease progression of GNE myopathy is steady, relatively slow and leads to loss of ambulation within 10–20 years from onset. A retrospective study on disease progression in genetically confirmed GNE myopathy patients (2006 to 2018). Informed consent obtained from all patients. Total = 127 of 122 families. Mutation pattern: Compound heterozygous (CH) = 77(69.4%), homozygous (HOM) and only heterozygous (HET) = 17 (15.3%) each, novel = 56 (50.5%). Distal kinase domain affected = 105/111 (94.6%); epimerase domain only = 5. Common Indian mutation V727 M = 93 (83.8%). CH mutations had V727 M in one allele except in one. Roma gypsy founder mutation (I618T) = 5 (HOM-4;CH-1). Other mutations (A555V and L732F in 4 each; Y392H, G502D, P58L and G599 V in 3 each). Ninety-three cases from 88 families were studied for progression. Men = 61(65.5%). Mean age at presentation: 33 ± 7.2 years (20–55), age at onset: 27 ± 6.1 years (14–46), duration of symptoms:6.2 ± 5.1 years (1–24), total duration at presentation: 8.6 ± 5.7 years (1–28); duration of follow-up: 8.9 ± 3.3 years (1–17); age at loss of ambulation in 4 cases = 30.0 ± 6.0 years. At last follow-up, 80 patients were independently ambulant, 11 required maximum support to walk (none ever used a cane), 2 were wheel chair bound. The course was slow in 81 (87.1%) and rapid in 12 (12.9%). The initial symptom was foot drop in 74/93 (79.6%). Hip muscle weakness present in90/93 (96.8%). Distal upper limb weakness = 68 (73.1%), proximal upper limb weakness in 25 (26.9%). Beevor's sign in 57(61.3%). This is the largest series of genetically confirmed GNE myopathy from a single center. Disease progression study shows that majority had a slow progression and were ambulant more than a decade after onset and this is similar to reports from Japan and UK.