Life-threatening muscle complications of COL4A1-related disorder

Brain Dev. 2020 Jan;42(1):93-97. doi: 10.1016/j.braindev.2019.09.001. Epub 2019 Sep 18.

Abstract

COL4A1-related disorder is recognized as a systemic disease because the alpha 1 chain of type IV collagen, encoded by COL4A1, is essential for basement membrane stability. However, muscular manifestations related to this disorder are rarely reported. We report the case of a 2-year-old boy with porencephaly, who harbored a de novo COL4A1 mutation of c.1853G > A, p. (Gly618Glu) and exhibited recurrent rhabdomyolysis with viral or bacterial infections. Moreover, he developed obstructive hypertrophic cardiomyopathy which required surgical intervention. Skeletal muscle biopsy revealed findings compatible with fiber-type disproportion. Ultrastructural study demonstrated the similar findings previously reported in mice with Col4a1 mutation including collagen disarray and reduction of electron density in the basement membrane of capillary endothelial cells and muscle fibers. Dilated endoplasmic reticulum in the capillary endothelial cells is also noted. This report adds another disease spectrum of COL4A1 mutation which include porencephaly, hypertrophic cardiomyopathy, rhabdomyolysis and fiber-type disproportion.

Keywords: COL4A1; Congenital fiber-type disproportion; Hypertrophic obstructive cardiomyopathy; Rhabdomyolysis.

Publication types

  • Case Reports

MeSH terms

  • Cardiomyopathy, Hypertrophic / genetics*
  • Child, Preschool
  • Collagen Type IV / genetics*
  • Humans
  • Male
  • Muscle, Skeletal / pathology*
  • Mutation
  • Porencephaly / genetics*
  • Rhabdomyolysis / genetics*

Substances

  • COL4A1 protein, human
  • Collagen Type IV