Nationwide patient registry for GNE myopathy in Japan

Abstract

BackgroundGNE myopathy is a slowly progressive autosomal recessive myopathy caused by mutations in the GNE (glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase) gene. This study aimed to (1) develop a nationwide patient registry for GNE myopathy in order to facilitate the planning of clinical trials and recruitment of candidates, and (2) gain further insight into the disease for the purpose of improving therapy and care.MethodsMedical records of genetically-confirmed patients with GNE myopathy at the National Center Hospital of the National Center of Neurology and Psychiatry (NCNP) were retrospectively reviewed in order to obtain data reflecting the severity and progression of the disease. We also referred to items in the datasheet of the nationwide registry of dystrophinopathy patients in the Registry of Muscular Dystrophies (Remudy). Items selected for the registration sheet included age, sex, age at onset, past history and complications, family history, body weight and height, pathological findings of muscle biopsy, grip power, walking ability, respiratory function, cardiac function, willingness to join upcoming clinical trials, and participation in patient associations. A copy of the original genetic analysis report was required of each patient.ResultsWe successfully established the Remudy-GNE myopathy. Currently, 121 patients are registered nationwide, and 93 physicians from 73 hospitals collaborated to establish the registry. The mean age at onset was 27.7 ± 9.6 years, and 19.8% (24/121) of patients could walk without assistance. Mean presumed durations from onset to use of assistive devices (cane and/or braces) and a wheelchair, and loss of ambulation were 12.4, 15.2, and 21.1 years, respectively. Three patients had a past history and/or complication of idiopathic thrombocytopenia. To share the progress of this study with the community, newsletters were published on a regular basis, and included information regarding new phase I clinical trials for GNE myopathy. The newsletters also served as a medium to bring attention to the importance of respiratory evaluation and care for respiratory insufficiency.ConclusionThe Japanese Remudy-GNE myopathy is useful for clarifying the natural history of the disease and recruiting patients with genetically-confirmed GNE myopathy for clinical trials.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0150-4) contains supplementary material, which is available to authorized users.

GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges

“…Cardiac involvement has been reported in a mouse model of GNE myopathy [21] but is not usually seen in patients. As part of the Japanese Registry of GNE myopathy, all 35 subjects who had an echocardiogram had normal cardiac function [22]. A cohort of Bulgarian Roma patients had cardiac abnormalities detected by electrocardiogram (EKG) (n = 12) or echocardiogram (n = 33), but most of these were subclinical or due to other predisposing factors [20].…”

“…Thrombocytopenia has been reported in a small number of patients with GNE myopathy [25,26], but one study determined the occurrence of thrombocytopenia was similar to that of the general population in Japan [10,22]. Congenital thrombocytopenia has also been reported in families with compound heterozygous GNE mutations, and although the etiology still needs to be determined, the authors suggested hyposialylation of platelets leading to increased platelet clearance as a possible mechanism [26,27].…”

215th ENMC International Workshop VCP-related multi-system proteinopathy (IBMPFD) 13–15 November 2015, Heemskerk, The Netherlands

“…However, these two are industry funded and thus any natural history study on VCP will have to have adequate funding to support such aims. Perhaps these can be run under the umbrella of TREAT-MND ALLIANCE, as exemplified by the Japanese GNE myopathy study [65]. Such a natural history study should address the current gaps, including natural history of the disease, variability in interfamilial as well as intrafamilial phenotypes, and provide phenotype–genotype correlations, information about disease modifiers and helpful biomarkers in the disease.…”

Identification of a GNE homozygous mutation in a Han‐Chinese family with GNE myopathy

“…It is a rare, recessively inherited, early adult‐onset myopathy . It is typically characterized by slow progression that preferentially affects the tibialis anterior muscles, commonly spares the quadriceps femoris muscles and gradually spreads to other muscles . GNE myopathy occurs worldwide.…”

“…1 It is typically characterized by slow progression that preferentially affects the tibialis anterior muscles, commonly spares the quadriceps femoris muscles and gradually spreads to other muscles. 2,3 GNE myopathy occurs worldwide. The prevalence ranges from 1/1 000 000 to 21/ 1 000 000, although it may be underestimated as many patients escape diagnosis.…”