Nonaka type Distal myopathy

A hereditary autosomal recessive muscular disorder with early adult onset that is characterized by weakness of the anterior compartment of the lower limbs, however the quadriceps muscles are spared. Numerous rimmed VACUOLES are present in muscle biopsy, but there appear to be no inflammatory cells. Mutations in the GNE gene have been identified; inclusion body myopathy 2 (OMIM: 600737) is an allelic disorder. OMIM: 605820

Also Known As:

Distal myopathy, Nonaka type; Distal Myopathy with Rimmed Vacuoles; Hereditary Inclusion Body Myopathy; Ibm2; Inclusion Body Myopathy 2; Myopathy, distal, with rimmed vacuoles; Nonaka Myopathy; Nonaka distal myopathy; Rimmed Vacuole Myopathy

Networked: 138 relevant articles (2 outcomes, 11 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease)
2.	Frontotemporal Dementia (Semantic Dementia)
3.	Nonaka type Distal myopathy
4.	Muscular Diseases (Myopathy)
5.	Myofibrillar Myopathy

Experts

1.	Nishino, Ichizo: 16 articles (09/2015 - 03/2004)
2.	Noguchi, Satoru: 13 articles (06/2014 - 03/2004)
3.	Malicdan, May Christine V: 10 articles (07/2012 - 10/2005)
4.	Gahl, William A: 8 articles (11/2011 - 03/2004)
5.	Huizing, Marjan: 8 articles (11/2011 - 03/2004)
6.	Hayashi, Yukiko K: 7 articles (07/2012 - 03/2004)
7.	Hinderlich, Stephan: 6 articles (07/2009 - 05/2004)
8.	Broccolini, Aldobrando: 5 articles (04/2015 - 02/2005)
9.	Mirabella, Massimiliano: 5 articles (04/2015 - 02/2005)
10.	Krause, Sabine: 5 articles (05/2010 - 12/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Nonaka type Distal myopathy:

1.	Proteins (Proteins, Gene)FDA Link 10/01/2023 - "The Arabidopsis RRM domain proteins EDM3 and IBM2 coordinate the floral transition and basal immune responses." 12/11/2014 - "Point mutations within IBM2 abolished leukemogenic transformation by MLL-AF9, validating that this newly identified motif is essential for the oncogenic activity of MLL fusion proteins. " 07/01/2009 - "An additional characteristic of GNE is its interaction with proteins involved in the regulation of development, which might play a crucial role in the hereditary inclusion body myopathy. " 11/01/2000 - "Increased lysosome-related proteins in the skeletal muscles of distal myopathy with rimmed vacuoles." 11/01/2008 - "However, despite the high homology between these two proteins, the biological role of BACE2 is still controversial, even though a few studies have suggested a pathogenetic role in sporadic inclusion-body myositis and hereditary inclusion-body myopathy, which are characterized by vacuolization of muscular fibers with intracellular deposits of proteins similar to those found in the brain of AD patients. "
2.	AcidsIBA 10/01/2023 - "[Efficacy of Aceneuramic Acid for Distal Myopathy with Rimmed Vacuoles]."
3.	Racemases and Epimerases (Epimerases and Racemases)IBA 04/01/2007 - "Heterozygous mutations affecting the epimerase domain of the GNE gene causing distal myopathy with rimmed vacuoles in a Taiwanese family." 12/01/2011 - "Biochemical characterization of the M712T-mutation of the UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosaminekinase in hereditary inclusion body myopathy." 01/01/2003 - "Because GNE is relatively weakly expressed in skeletal muscle cells, and involvement of other organs are not clinically evident in patients affected with IBM2, it is likely that the missense mutation(s) found in these patients cause a partial reduction of the efficiency of either the epimerase or the kinase activity of this enzyme. " 01/01/2019 - "UDP N-acetylglucosamine2-epimerase/N-acetylmannosamine-kinase (GNE) gene mutations can cause mostly autosomal-recessive myopathy with juvenile-onset known as hereditary inclusion-body myopathy (HIBM). " 01/01/2002 - "Mutations associated with sialuria are located in the epimerase domain, and those associated with IBM2 are in the epimerase or the kinase domain or both, whereas the mutations we observed in the Nonaka myopathy patients were located in the sugar kinase domain of the gene. "
4.	Uridine Diphosphate (UDP)IBA 12/01/2011 - "Biochemical characterization of the M712T-mutation of the UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosaminekinase in hereditary inclusion body myopathy." 01/01/2019 - "UDP N-acetylglucosamine2-epimerase/N-acetylmannosamine-kinase (GNE) gene mutations can cause mostly autosomal-recessive myopathy with juvenile-onset known as hereditary inclusion-body myopathy (HIBM). " 04/01/2007 - "Studies of distal myopathy with rimmed vacuoles (DMRV) revealed that most patients had mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. " 05/11/2004 - "Study of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE) revealed that almost all cases of distal myopathy with rimmed vacuoles were caused by GNE mutations. " 07/08/2015 - "Muscle biopsy and UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene mutation analysis in two Chinese patients with distal myopathy with rimmed vacuoles."
5.	N-acylmannosamine kinaseIBA 05/01/2012 - "We report novel compound heterozygous mutations of the UDP-N-acetylglucosamine-2-epimerase and N-acetylmannosamine kinase (GNE) gene, c.302G>A (p.R101H) and c.617-4A>G, in a Japanese family with distal myopathy with rimmed vacuoles (DMRV) presenting with slow progression. " 11/01/2005 - "Use of a cell-free system to determine UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities in human hereditary inclusion body myopathy." 01/01/2014 - "Distal myopathy with rimmed vacuoles (DMRV) is an autosomal recessive or sporadic early adult-onset myopathy caused by mutations in the UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase (GNE) gene. " 01/01/2019 - "UDP N-acetylglucosamine2-epimerase/N-acetylmannosamine-kinase (GNE) gene mutations can cause mostly autosomal-recessive myopathy with juvenile-onset known as hereditary inclusion-body myopathy (HIBM). " 04/01/2007 - "Studies of distal myopathy with rimmed vacuoles (DMRV) revealed that most patients had mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. "
6.	AcetylglucosamineIBA 12/01/2011 - "Biochemical characterization of the M712T-mutation of the UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosaminekinase in hereditary inclusion body myopathy." 04/01/2007 - "Studies of distal myopathy with rimmed vacuoles (DMRV) revealed that most patients had mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. " 05/11/2004 - "Study of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE) revealed that almost all cases of distal myopathy with rimmed vacuoles were caused by GNE mutations. " 07/08/2015 - "Muscle biopsy and UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene mutation analysis in two Chinese patients with distal myopathy with rimmed vacuoles." 02/01/2011 - "Homozygous mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene cause hereditary inclusion body myopathy type 2 (HIBM2). "
7.	N-Acetylneuraminic Acid (Sialic Acid)IBA 09/01/2015 - "[Sialic Acid Replacement Therapy for Distal Myopathy with Rimmed Vacuoles]." 03/01/2012 - "[Sialic Acid supplementation therapy for distal myopathy with rimmed vacuoles]." 01/01/2012 - "[Sialic acid supplementation therapy for distal myopathy with rimmed vacuoles (GNE myopathy)]." 02/01/2003 - "Hereditary inclusion body myopathy and Nonaka myopathy result from defects in sialic acid production. " 06/01/2014 - "Several studies in humans have been performed regarding changes in sialic acid expression in a particular pathology, hereditary inclusion body myopathy, leading to muscular weakness and atrophy, with a similar phenomenon appearing also in sarcopenia of aging. "
8.	SugarsIBA 06/01/2010 - "[Animal model of distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy and preclinical trial with sugar compounds]." 03/01/2010 - "A preclinical trial of sialic acid metabolites on distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy, a sugar-deficient myopathy: a review." 01/01/2002 - "Mutations associated with sialuria are located in the epimerase domain, and those associated with IBM2 are in the epimerase or the kinase domain or both, whereas the mutations we observed in the Nonaka myopathy patients were located in the sugar kinase domain of the gene. "
9.	EnzymesIBA 06/01/2004 - "This bifunctional enzyme is involved in the development of different diseases like sialuria or hereditary inclusion body myopathy. " 05/01/2012 - "Hereditary inclusion body myopathy (HIBM) is a young-adult onset autosomal recessive disorder caused by a hypomorphic rate limiting enzyme of sialic acid biosynthesis. " 06/18/2008 - "Hereditary inclusion body myopathy (HIBM) is a rare neuromuscular disorder caused by mutations in GNE, the key enzyme in the biosynthetic pathway of sialic acid. " 11/01/2002 - "These findings further confirm that homozygous or compound heterozygous mutations of GNE/MNK gene associated with IBM2 are not confined to any single specific region of the enzyme outside its negative feedback regulatory domain located at codons 249-275." 01/01/2017 - "GNE myopathy (GNEM), also known as hereditary inclusion body myopathy (HIBM), is a late- onset, progressive myopathy caused by mutations in the GNE gene encoding the enzyme responsible for the first regulated step in the biosynthesis of sialic acid (SA). "
10.	DesminIBA 03/01/1991 - "Auriculo-ventricular block and distal myopathy with rimmed vacuoles and desmin storage." 12/01/2010 - "Suspected cases of mitochondrial neurogastrointestinal encephalopathy (MNGIE), myofibrillar myopathy (MFM) and distal myopathy with rimmed vacuoles (DMRV) were confirmed by molecular genetic studies examining thymidine phosphorylase, GNE, ZASP myotilin, desmin, abeta-crystalline and filamin C genes. " 03/01/2007 - "In desmin myopathy but not hereditary inclusion-body myopathy (hIBM), there is accumulation of myofibrillar proteins including desmin, myotilin, dystrophin, gelsolin, actin, and CDC kinase. "

Therapies and Procedures

1.	Transcutaneous Electric Nerve Stimulation (TENS) 06/30/2011 - "A hydroponics-based genetical genomics study in roots of a Zea mays IBM2 Syn10 double haploid population identified tens of thousands of cis-acting and trans-acting eQTL. "
2.	Therapeutics 12/01/2019 - "Although clinically distinct from sporadic IBM, preclinical models of hereditary inclusion body myopathy have offered an opportunity to move some therapies toward clinical development. " 05/01/2010 - "Hereditary inclusion body myopathy: single patient response to GNE gene Lipoplex therapy." 11/01/2009 - "[Development of therapy for distal myopathy with rimmed vacuoles]." 09/01/2009 - "Hereditary inclusion-body myopathy: clues on pathogenesis and possible therapy." 10/01/2008 - "The hereditary inclusion body myopathy enigma and its future therapy."
3.	Orthopedic Procedures 06/01/1998 - "Seeking evidence of transport abnormalities in distal myopathy with rimmed vacuoles (DMRV), we performed immunohistochemistry for clathrin in muscle biopsy specimens from patients with this disorder or other neuromuscular disorders, and also in control muscle samples resected in orthopedic procedures. "
4.	Denervation 10/05/1998 - "To investigate whether abnormally accumulated betaAPP may be responsible for denervation of muscle fibers that are present in hereditary inclusion-body myopathy (h-IBM) and sporadic inclusion-body myositis (s-IBM), we cultured five h-IBM and eight normal muscle biopsies. "