Hereditary Inclusion Body Myopathy (HIBM)

HIBM is an adult-onset, autosomal recessive disorder, characterized by slow progression of muscle weakness, both distal and proximal, but with the unusual feature of relative sparing of the quadriceps even in the advanced stages of the disease. The first symptoms usually involve weakness of the lower extremities, with affected individuals often presenting with foot drop. Age-of-onset ranges from late teens to the fourth decade. Severe incapacitation usually occurs within 10-20 years of disease onset, although the quadriceps sparing often allows patients to remain ambulatory until very late in the course of disease. Muscle biopsy from affected individuals show a typical rimmed vacuole myopathy with cytoplasmic inclusions of 15-18nm filaments. Mutations in the GNE gene, coding for the enzyme, UDP-N-Acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, cause at least three disorders: HIBM, Nonaka myopathy, and a rare dominant inborn error of metabolism, sialuria (MIM: 269921). The enzyme is bifunctional and catalyzes the first two steps in the biosynthesis of sialic acid. The epimerase enzyme activity is mediated by the amino-terminus of the enzyme and converts UDP-GlcNAc into ManNAc. The kinase activity is mediated by the carboxyterminus and converts ManNAc into ManNAc-6P. Missense mutations associated with the dominant disorder sialuria result in loss of feedback inhibition of the epimerase domain. Missense mutations associated with the recessive disorders HIBM and Nonaka myopathy may affect either the epimerase or kinase domain.

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ACTA1, ANO5, ASAH1, ATP2A1, B3GALNT2, B4GAT1, BAG3, BICD2, BIN1, BVES, CACNA1S, CAPN3, CAV3, CCDC78, CFL2, CHKB, CLCN1, CNTN1, COL12A1, COL6A1, COL6A2, COL6A3, CRYAB, DAG1, DES, DMD, DNAJB2, DNAJB6, DNM2, DOK7, DPM1, DPM2, DPM3, DYNC1H1, DYSF, EGR2, EMD, FHL1, FKRP, FKTN, FLNC, GAA, GBE1, GMPPB, GNE, IGHMBP2, ISPD, ITGA7, KBTBD13, KLHL40, KLHL41, LAMA2, LAMP2, LARGE, LDB3, LMNA, LMOD3, MEGF10, MICU1, MTM1, MYH2, MYH7, MYOT, NEB, PHKA1, PLEC, PLEKHG5, POMGNT1, POMK, POMT1, POMT2, PYGM, RYR1, SCN4A, SEPN1, SGCA, SGCB, SGCD, SGCG, SIL1, SLC52A2, SLC52A3, SYNE1, TCAP, TMEM5, TNNI2, TNNT1, TNPO3, TOR1AIP1, TPM2, TPM3, TRAPPC11, TRIM32, TRIP4, TRPV4, TTN, UBA1, VCP, VRK1
  • Molecular confirmation of a clinical diagnosis
  • Identification of at-risk family members
  • Assist with treatment/ management decisions
  • Recurrence risk assessment
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

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