What causes glycosylation-related congenital muscular dystrophy (CMD)?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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These are rare, autosomal recessive disorders in the metabolism of dolichols. [49]

Dolichol (a-saturated polyprenol) is present in all tissues and most organelle membranes. It functions as a carbohydrate donor to growing oligosaccharide chains of glycoproteins and glycolipids. This includes N-linked protein glycosylation of a-dystroglycan.

Mutations in 3 genes have been reported to cause a congenital muscular dystrophy phenotype:

  • DOLK (DK1) -Dolichol kinase mutation results in microcephaly, ichthyosis, seizures, hypotonia, elevated CK, liver dysfunction, and progressive dilated cardiomyopathy. [49] A separate report highlighted a primary cardiac presentation with dilated cardiomyopathy and life-threatening dysrhythmias. [50]

  • DPM2 – Dolichol-phosphate mannosyltransferase 2 mutation described in 3 patients results in microcephaly, hypotonia, elevated CK, elevated transaminases, difficulty swallowing, seizures, cerebellar hypoplasia, cortical visual impairment without structural eye abnormality, and muscle biopsy showing marked reduction in O-mannosylglycans on a-dystroglycan. [51]

  • DPM3 -Dolichol-phosphate mannosyltransferase 3mutation described in 1 patient resulted in mild intellectual impairment. [52] Mild weakness was noted at age 11 years. At age 20 years, there was dilated cardiomyopathy, elevated CK, muscle biopsy with markedly reduced glycosylation of a-dystroglycan, and normal brain MRI.

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