Abstract
Background
Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy, also called distal myopathy with rimmed
vacuoles (DMRV) or hereditary inclusion body myopathy (HIBM), is a rare, progressive
autosomal recessive disorder caused by mutations in the GNE gene. Here, we examined the relationship between genotype and clinical phenotype
in participants with GNE myopathy.
Methods
Participants with GNE myopathy were asked to complete a questionnaire regarding medical
history and current symptoms.
Results
A total of 71 participants with genetically confirmed GNE myopathy (27 males and 44
females; mean age, 43.1±13.0 (mean±SD) years) completed the questionnaire. Initial symptoms (e.g., foot drop and lower limb weakness) appeared at a mean age of 24.8±8.3 years. Among the 71 participants, 11 (15.5%) had the ability to walk, with a median
time to loss of ambulation of 17.0±2.1 years after disease onset. Participants with a homozygous mutation (p.V572L) in the
N-acetylmannosamine kinase domain (KD/KD participants) had an earlier disease onset
compared to compound heterozygous participants with mutations in the uridine diphosphate-N-acetylglucosamine
(UDP-GlcNAc) 2-epimerase and N-acetylmannosamine kinase domains (ED/KD participants; 26.3±7.3 vs. 21.2±11.1 years, respectively). KD/KD participants were more frequently non-ambulatory compared
to ED/KD participants at the time of survey (80% vs. 50%). Data were verified using
medical records available from 17 outpatient participants.
Conclusions
Homozygous KD/KD participants exhibited a more severe phenotype compared to heterozygous
ED/KD participants.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Autosomal recessive distal muscular dystrophy: a comparative study with distal myopathy with rimmed vacuole formation.Ann Neurol. 1985; 17: 51-59
- “Rimmed vacuole myopathy” sparing the quadriceps. A unique disorder in Iranian Jews.J Neurol Sci. 1984; 64: 33-43
- Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy.Neurology. 2002; 59: 1689-1693
- The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy.Nat Genet. 2001; 29: 83-87
- Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE).J Hum Genet. 2002; 47: 77-79
- UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation.Science. 1999; 284: 1372-1376
- Recent advances in distal myopathy with rimmed vacuoles (DMRV) or hIBM: treatment perspectives.Curr Opin Neurol. 2008; 21: 596-600
- Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles.J Biol Chem. 2004; 279: 11402-11407
- Hyposialylation of neprilysin possibly affects its expression and enzymatic activity in hereditary inclusion—body myopathy muscle.J Neurochem. 2008; 105: 971-981
- No overall hyposialylation in hereditary inclusion body myopathy myoblasts carrying the homozygous M712T GNE mutation.Biochem Biophys Res Commun. 2005; 328: 221-226
- A Gne knockout mouse expressing human GNE D176V mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy.Hum Mol Genet. 2007; 16: 2669-2682
- Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the GNE myopathy mouse model.Nat Med. 2009; 15: 690-695
- Hereditary inclusion body myopathy: the Middle Eastern genetic cluster.Neurology. 2003; 60: 1519-1523
- Distal myopathy with rimmed vacuoles (DMRV): new GNE mutations and splice variant.Neurology. 2004; 11: 1607-1610
- GNE mutations causing distal myopathy with rimmed vacuoles with inflammation.Neurology. 2003; 12: 384-386
- Heterozygous mutations affecting the epimerase domain of the GNE gene causing distal myopathy with rimmed vacuoles in a Taiwanese family.Clin Neurol Neurosurg. 2007; 109: 250-256
- Phenotypic variability in a Chinese family with rimmed vacuolar distal myopathy.J Neurol Neurosurg Psychiatry. 2005; 76: 752-755
- Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients.Brain. 2005; 128: 671-677
- The changing natural history of spinal muscular atrophy type 1.Neurology. 2007; 69: 1931-1936
- Classification of the gait patterns of boys with Duchenne muscular dystrophy and their relationship to function.J Child Neurol. 2010; 25: 1103-1109
- Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the quadriceps.Hum Mutat. 2003; 21: 99
Article info
Publication history
Published online: April 16, 2012
Accepted:
March 21,
2012
Received in revised form:
March 20,
2012
Received:
January 10,
2012
Identification
Copyright
© 2012 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
