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GNE myopathy(NM)

MedGen UID:
381298
Concept ID:
C1853926
Disease or Syndrome
Synonyms: IBM 2; Inclusion body myopathy 2; INCLUSION BODY MYOPATHY 2, AUTOSOMAL RECESSIVE; Inclusion body myopathy autosomal recessive; Inclusion body myopathy quadriceps sparing; INCLUSION BODY MYOPATHY, HEREDITARY, AUTOSOMAL RECESSIVE; MYOPATHY, DISTAL, WITH OR WITHOUT RIMMED VACUOLES; NM; Nonaka distal myopathy; Nonaka myopathy
SNOMED CT: Hereditary inclusion body myopathy (702382000); Rimmed vacuole myopathy (702382000); Inclusion body myopathy 2 (702382000); Distal myopathy with rimmed vacuoles (702382000); Quadricep sparing inclusion body myopathy (702382000); Nonaka myopathy (702382000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): GNE (9p13.3)
 
Monarch Initiative: MONDO:0011603
OMIM®: 605820
Orphanet: ORPHA602

Disease characteristics

Excerpted from the GeneReview: GNE Myopathy
GNE myopathy is a slowly progressive muscle disease that typically presents between age 20 and 40 years with bilateral foot drop caused by anterior tibialis weakness. Lower-extremity muscle involvement progresses from the anterior to the posterior compartment of the lower leg, followed by hamstrings, then hip girdle muscles, with relative sparing of the quadriceps. A wheelchair may be needed about ten to 20 years after the onset of manifestations. The upper extremities, which may be affected within five to ten years of disease onset, do not necessarily follow a distal-to-proximal progression. In advanced stages, neck and core muscles can become affected. [from GeneReviews]
Authors:
Nuria Carrillo  |  May Christine Malicdan  |  Marjan Huizing   view full author information

Additional descriptions

From OMIM
Nonaka myopathy (NM) is an autosomal recessive progressive adult-onset myopathy with a predeliction for distal muscle involvement, usually affecting the lower limbs and resulting in gait abnormalities or loss of ambulation. Some individuals may have involvement of the upper limbs or proximal muscles (Argov et al., 2003). In rare cases (up to 2.5%), the myopathy can be associated with mild, asymptomatic thrombocytopenia, as observed in the allelic disorder THC12 (summary by Revel-Vilk et al., 2018). Historically, the disorder has had several different names, including distal myopathy with rimmed vacuoles, inclusion body myopathy, and quadriceps-sparing myopathy. Huizing et al. (2014) proposed using the term 'GNE myopathy' to refer to this disorder.  http://www.omim.org/entry/605820
From MedlinePlus Genetics
GNE myopathy is a condition that primarily affects skeletal muscles, which are muscles that the body uses for movement. This disorder causes muscle weakness that appears in late adolescence or early adulthood and worsens over time.

Difficulty lifting the front part of the foot (foot drop) is often the first sign of GNE myopathy. For individuals with GNE myopathy, foot drop is caused by weakness of a muscle in the lower leg called the tibialis anterior. This muscle helps raise the foot up. Weakness in the tibialis anterior alters the way a person walks and makes it difficult to run and climb stairs. As the disorder progresses, weakness also develops in the muscles of the upper legs, hips, shoulders, and hands. Unlike most forms of myopathy, GNE myopathy usually does not affect the quadriceps, which are a group of large muscles at the front of the thigh. This condition also does not affect the muscles of the eye or heart, and it does not cause neurological problems. Weakness in leg muscles makes walking increasingly difficult, and most people with GNE myopathy require wheelchair assistance within 20 years after the signs and symptoms of the disorder appear.

People with the characteristic features of GNE myopathy have been described in several different populations. When the condition was first reported in Japanese families, researchers called it distal myopathy with rimmed vacuoles (DMRV) or Nonaka myopathy. When a similar disorder was discovered in Iranian Jewish families, researchers called it rimmed vacuole myopathy or hereditary inclusion body myopathy (HIBM). It has since become clear that these conditions are variations of a single disorder caused by changes in the same gene.  https://medlineplus.gov/genetics/condition/gne-myopathy

Clinical features

From HPO
Distal lower limb muscle weakness
MedGen UID:
324514
Concept ID:
C1836450
Finding
Reduced strength of the distal musculature of the legs.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Rimmed vacuoles
MedGen UID:
340089
Concept ID:
C1853932
Finding
Presence of abnormal vacuoles (membrane-bound organelles) in the sarcolemma. On histological staining with hematoxylin and eosin, rimmed vacuoles are popcorn-like clear vacuoles with a densely blue rim. The vacuoles are often associated with cytoplasmic and occasionally intranuclear eosinophilic inclusions.
Deposits immunoreactive to beta-amyloid protein
MedGen UID:
343012
Concept ID:
C1853934
Finding
EMG: myopathic abnormalities
MedGen UID:
867362
Concept ID:
C4021726
Pathologic Function
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Rao D, Ganguli M
J Biosci 2024;49 PMID: 38383972
Mair D, Biskup S, Kress W, Abicht A, Brück W, Zechel S, Knop KC, Koenig FB, Tey S, Nikolin S, Eggermann K, Kurth I, Ferbert A, Weis J
Brain Pathol 2020 Sep;30(5):877-896. Epub 2020 Jun 15 doi: 10.1111/bpa.12864. PMID: 32419263Free PMC Article
Pogoryelova O, Cammish P, Mansbach H, Argov Z, Nishino I, Skrinar A, Chan Y, Nafissi S, Shamshiri H, Kakkis E, Lochmüller H
Neuromuscul Disord 2018 Feb;28(2):158-168. Epub 2017 Nov 14 doi: 10.1016/j.nmd.2017.11.001. PMID: 29305133Free PMC Article

Recent clinical studies

Etiology

Mori-Yoshimura M, Suzuki N, Katsuno M, Takahashi MP, Yamashita S, Oya Y, Hashizume A, Yamada S, Nakamori M, Izumi R, Kato M, Warita H, Tateyama M, Kuroda H, Asada R, Yamaguchi T, Nishino I, Aoki M
Orphanet J Rare Dis 2023 Aug 11;18(1):241. doi: 10.1186/s13023-023-02850-y. PMID: 37568154Free PMC Article
Wang M, Yang H, Lin Z, Li X, Liu L, Huang S, Zhao H, Zhu X, Xiao Q, Duan R, Wang J, Zuchner S, Tang B, Zhang R
J Neurol 2023 Oct;270(10):4959-4967. Epub 2023 Jun 26 doi: 10.1007/s00415-023-11821-z. PMID: 37365282
Murtazina A, Nikitin S, Rudenskaya G, Sharkova I, Borovikov A, Sparber P, Shchagina O, Chukhrova A, Ryzhkova O, Shatokhina O, Orlova A, Udalova V, Kanivets I, Korostelev S, Polyakov A, Dadali E, Kutsev S
Genes (Basel) 2022 Oct 31;13(11) doi: 10.3390/genes13111991. PMID: 36360228Free PMC Article
Lv XQ, Xu L, Lin PF, Yan CZ
Neurol Sci 2022 Jul;43(7):4483-4491. Epub 2022 Feb 9 doi: 10.1007/s10072-022-05938-8. PMID: 35138478
Broccolini A, Mirabella M
Biochim Biophys Acta 2015 Apr;1852(4):644-50. Epub 2014 Aug 19 doi: 10.1016/j.bbadis.2014.08.007. PMID: 25149037

Diagnosis

Wang M, Yang H, Lin Z, Li X, Liu L, Huang S, Zhao H, Zhu X, Xiao Q, Duan R, Wang J, Zuchner S, Tang B, Zhang R
J Neurol 2023 Oct;270(10):4959-4967. Epub 2023 Jun 26 doi: 10.1007/s00415-023-11821-z. PMID: 37365282
Beecher G, Fleming MD, Liewluck T
Muscle Nerve 2022 Apr;65(4):374-390. Epub 2022 Jan 5 doi: 10.1002/mus.27474. PMID: 34985130
Carrillo N, Malicdan MC, Huizing M
Neurotherapeutics 2018 Oct;15(4):900-914. doi: 10.1007/s13311-018-0671-y. PMID: 30338442Free PMC Article
Nishino I, Carrillo-Carrasco N, Argov Z
J Neurol Neurosurg Psychiatry 2015 Apr;86(4):385-92. Epub 2014 Jul 7 doi: 10.1136/jnnp-2013-307051. PMID: 25002140Free PMC Article
Celeste FV, Vilboux T, Ciccone C, de Dios JK, Malicdan MC, Leoyklang P, McKew JC, Gahl WA, Carrillo-Carrasco N, Huizing M
Hum Mutat 2014 Aug;35(8):915-26. doi: 10.1002/humu.22583. PMID: 24796702Free PMC Article

Therapy

Park YE, Park E, Choi J, Go H, Park DB, Kim MY, Sung NJ, Kim L, Shin JH
Biomed Pharmacother 2023 Dec;168:115689. Epub 2023 Oct 16 doi: 10.1016/j.biopha.2023.115689. PMID: 37852099
Mori-Yoshimura M, Suzuki N, Katsuno M, Takahashi MP, Yamashita S, Oya Y, Hashizume A, Yamada S, Nakamori M, Izumi R, Kato M, Warita H, Tateyama M, Kuroda H, Asada R, Yamaguchi T, Nishino I, Aoki M
Orphanet J Rare Dis 2023 Aug 11;18(1):241. doi: 10.1186/s13023-023-02850-y. PMID: 37568154Free PMC Article
Yoshioka W, Nishino I, Noguchi S
Curr Opin Neurol 2022 Oct 1;35(5):629-636. Epub 2022 Aug 11 doi: 10.1097/WCO.0000000000001090. PMID: 35959526
Pogoryelova O, González Coraspe JA, Nikolenko N, Lochmüller H, Roos A
Orphanet J Rare Dis 2018 May 2;13(1):70. doi: 10.1186/s13023-018-0802-x. PMID: 29720219Free PMC Article
Nishino I, Carrillo-Carrasco N, Argov Z
J Neurol Neurosurg Psychiatry 2015 Apr;86(4):385-92. Epub 2014 Jul 7 doi: 10.1136/jnnp-2013-307051. PMID: 25002140Free PMC Article

Prognosis

Mitrani-Rosenbaum S, Attali R, Argov Z
Neuromuscul Disord 2023 Oct;33(10):762-768. Epub 2023 Aug 27 doi: 10.1016/j.nmd.2023.08.013. PMID: 37666692
Van Wart S, Mager DE, Bednasz CJ, Huizing M, Carrillo N
Drugs R D 2021 Jun;21(2):189-202. Epub 2021 Apr 24 doi: 10.1007/s40268-021-00343-6. PMID: 33893973Free PMC Article
Khadilkar SV, Chaudhari AD, Singla MB, Dastur RS, Gaitonde PS, Bhutada AG, Hegde MR
Muscle Nerve 2021 Feb;63(2):199-203. Epub 2020 Nov 28 doi: 10.1002/mus.27117. PMID: 33197058
Celeste FV, Vilboux T, Ciccone C, de Dios JK, Malicdan MC, Leoyklang P, McKew JC, Gahl WA, Carrillo-Carrasco N, Huizing M
Hum Mutat 2014 Aug;35(8):915-26. doi: 10.1002/humu.22583. PMID: 24796702Free PMC Article
Li H, Chen Q, Liu F, Zhang X, Li W, Liu S, Zhao Y, Gong Y, Yan C
PLoS One 2013;8(3):e58116. Epub 2013 Mar 5 doi: 10.1371/journal.pone.0058116. PMID: 23472144Free PMC Article

Clinical prediction guides

Park YE, Park E, Choi J, Go H, Park DB, Kim MY, Sung NJ, Kim L, Shin JH
Biomed Pharmacother 2023 Dec;168:115689. Epub 2023 Oct 16 doi: 10.1016/j.biopha.2023.115689. PMID: 37852099
Mori-Yoshimura M, Suzuki N, Katsuno M, Takahashi MP, Yamashita S, Oya Y, Hashizume A, Yamada S, Nakamori M, Izumi R, Kato M, Warita H, Tateyama M, Kuroda H, Asada R, Yamaguchi T, Nishino I, Aoki M
Orphanet J Rare Dis 2023 Aug 11;18(1):241. doi: 10.1186/s13023-023-02850-y. PMID: 37568154Free PMC Article
Murtazina A, Nikitin S, Rudenskaya G, Sharkova I, Borovikov A, Sparber P, Shchagina O, Chukhrova A, Ryzhkova O, Shatokhina O, Orlova A, Udalova V, Kanivets I, Korostelev S, Polyakov A, Dadali E, Kutsev S
Genes (Basel) 2022 Oct 31;13(11) doi: 10.3390/genes13111991. PMID: 36360228Free PMC Article
Margeta M
Annu Rev Pathol 2020 Jan 24;15:261-285. Epub 2019 Oct 8 doi: 10.1146/annurev-pathmechdis-012419-032618. PMID: 31594457
Celeste FV, Vilboux T, Ciccone C, de Dios JK, Malicdan MC, Leoyklang P, McKew JC, Gahl WA, Carrillo-Carrasco N, Huizing M
Hum Mutat 2014 Aug;35(8):915-26. doi: 10.1002/humu.22583. PMID: 24796702Free PMC Article

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