Defective GNE causes sialuria, NK and IBM2

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). Sialuria is characterised by a large cytoplasmic accumulation and urinary excretion of Neu5Ac. 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. 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.

Summary from Reactome (R-HSA-4085011), read 2026-09-23.