Defective GNE causes sialuria, NK and IBM2

Stable Identifier
Homo sapiens
Defective GNE causes sialuria, Nonaka myopathy and inclusion body myopathy 2
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Sialuria (MIM:269921) is caused by a metabolic defect where the UDP?N?acetylglucosamine 2?epimerase, N?acetylmannosamine kinase (GNE) gene lacks feedback inhibition resulting in constitutive overproduction of free sialic acid (Neu5Ac) (Montreuil et al. 1968, Fontaine et al. 1968). Sialuria is characterised by a large cytoplasmic accumulation and urinary excretion of Neu5Ac (Kamerling et al. 1979). Sialurias differ from sialidoses, in which there is storage and excretion of 'bound' Neu5Ac. Defects in GNE also cause Nonaka myopathy (NK; MIM:605820), an early adult-onset disorder characterised by muscle weakness and wasting of distal muscles, especially the anterior tibial muscles (Nonaka et al. 1981, Asaka et al. 2001). Defects in GNE also cause inclusion body myopathy 2 (IBM2; MIM:600737), an autosomal recessive disorder with a similar phenotype to Nonaka myopathy (NK). IBM2 is an adult-onset, proximal and distal muscle weakness and wasting disorder. Muscle biospsy reveals from sufferers shows a rimmed vacuole myopathy and the degenerating muscle fibers contained abnormal amounts of beta-amyloid protein such as that found in neurodegenerative diorders. However, there is no neurological symptoms in these patients (Argov & Yarom 1984).

Literature References
PubMed ID Title Journal Year
7252518 Familial distal myopathy with rimmed vacuole and lamellar (myeloid) body formation

Ishiura, S, Nonaka, I, Sunohara, N, Satoyoshi, E

J. Neurol. Sci. 1981
444571 2-Acetamidoglucal, a new metabolite isolated from the urine of a patient with sialuria

Kamerling, JP, Haverkamp, J, Dorland, L, Strecker, G, Farriaux, JP, Vliegenthart, JF

Biochim. Biophys. Acta 1979
5658957 [Description of a new type of melituria, called sialuria]

Spik, G, Biserte, G, Fontaine, G, Montreuil, J, Strecker, G, Farriaux, JP

Clin. Chim. Acta 1968
11721884 Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy)

Takamori, M, Takizawa, Y, Komai, K, Tanaka, H, Matsushima, A, Shinagawa, M, Oyake, T, Satake, R, Saito, T, Namba, R, Tanaka, K, Asaka, T, Ikeuchi, K, Sunohara, N, Konagaya, M, Suenaga, A, Honke, K, Nitta, E, Uyama, E, Tsuji, S, Endo, K, Okino, S, Takada, H, Higuchi, S, Yoshimura, T, Nishina, M

J. Hum. Genet. 2001
5678410 [Sialuria: an original metabolic disorder]

Biserte, G, Fontaine, G, Montreuil, J, Farriaux, JP, Dupont, A

Helv Paediatr Acta 1968
6737002 "Rimmed vacuole myopathy" sparing the quadriceps. A unique disorder in Iranian Jews

Yarom, R, Argov, Z

J. Neurol. Sci. 1984
Name Identifier Synonyms
sialuria DOID:3659
inclusion body myositis DOID:3429 Inclusion body myositis (disorder), inclusion body myositis
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