What causes GMPPB-associated congenital muscular dystrophy (CMD)?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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Answer

Using exome and Sanger sequencing, homozygous or heterozygous mutations in Mannose-1-phophate guanyltransferase beta (GMPPB) were found in patients with a severe congenital muscular dystrophy or a milder limb-girdle muscular dystrophy phenotype. [48]

  • Presentation is from birth to 4 years, usually with hypotonia, spasticity, microcephaly, poor head control, feeding difficulties, and weakness.

  • All patients but one (presented at 4 years) had intellectual delay, often severe.

  • Epilepsy and motor delay were common.

  • CK was elevated to 630-8450 U/L.

  • Ophthalmologic findings include retinal dysfunction, cataracts, strabismus, nystagmus, and ptosis.

  • MRI findings include pontine and cerebellar hypoplasia, although 4 patients had no abnormalities.

  • Muscle biopsy showed reduced a-dystroglycan glycosylation.

Morpholino knockdown of zebrafish GMPPB caused hydrocephalus and muscular dystrophy.

GMPPB catalyzes the synthesis of GDP-mannose from GTP and mannose-1-phosphate. GDP-mannose is required for O-mannosylation of proteins, including a-dystroglycan.


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