GNE Myopathy: Current Update and Future Therapy

Overview

Journal J Neurol Neurosurg Psychiatry

Publisher BMJ Publishing Group

Specialties Neurology
Neurosurgery
Psychiatry

Date 2014 Jul 9

PMID 25002140

Citations 67

Authors

Ichizo Nishino

Nuria Carrillo-Carrasco

Zohar Argov

Affiliations

Soon will be listed here.

Abstract

GNE myopathy is an autosomal recessive muscle disease caused by biallelic mutations in GNE, a gene encoding for a single protein with key enzymatic activities, UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase, in sialic acid biosynthetic pathway. The diagnosis should be considered primarily in patients presenting with distal weakness (foot drop) in early adulthood (other onset symptoms are possible too). The disease slowly progresses to involve other lower and upper extremities' muscles, with marked sparing of the quadriceps. Characteristic findings on biopsies of affected muscles include 'rimmed' (autophagic) vacuoles, aggregation of various proteins and fibre size variation. The diagnosis is confirmed by sequencing of the GNE gene. Note that we use a new mutation nomenclature based on the longest transcript (GenBank: NM_001128227), which encodes a 31-amino acid longer protein than the originally described one (GenBank: NM_005476), which has been used previously in most papers. Based upon the pathophysiology of the disease, recent clinical trials as well as early gene therapy trials have evaluated the use of sialic acid or N-acetylmannosamine (a precursor of sialic acid) in patients with GNE myopathy. Now that therapies are under investigation, it is critical that a timely and accurate diagnosis is made in patients with GNE myopathy.

Citing Articles

Novel biallelic GNE variants identified in a patient with chronic thrombocytopenia without any symptoms of myopathy.

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PMID: 39576359 DOI: 10.1007/s00277-024-06104-0.

GNE Myopathy: Genotype - Phenotype Correlation and Disease Progression in an Indian Cohort.

Baskar D, Reddy N, Preethish-Kumar V, Polavarapu K, Nishadham V, Vengalil S J Neuromuscul Dis. 2024; 11(5):959-968.

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Recessive Mutations in Korean Nonaka Distal Myopathy Patients with or without Peripheral Neuropathy.

Tamanna N, Pi B, Lee A, Kanwal S, Choi B, Chung K Genes (Basel). 2024; 15(4).

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Efficacy confirmation study of aceneuramic acid administration for GNE myopathy in Japan.

Mori-Yoshimura M, Suzuki N, Katsuno M, Takahashi M, Yamashita S, Oya Y Orphanet J Rare Dis. 2023; 18(1):241.

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Development of Assays to Measure GNE Gene Potency and Gene Replacement in Skeletal Muscle.

Zygmunt D, Lam P, Ashbrook A, Koczwara K, Lek A, Lek M J Neuromuscul Dis. 2023; 10(5):797-812.

PMID: 37458043 PMC: 10578240. DOI: 10.3233/JND-221596.

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