Cutaneous dyspigmentation in patients with ganglioside GM3 synthase deficiency

Am J Med Genet A. 2013 Apr;161A(4):875-9. doi: 10.1002/ajmg.a.35826. Epub 2013 Feb 22.


Ganglioside GM3 synthase deficiency is a rare autosomal recessive metabolic disorder characterized by infantile onset of severe irritability and epilepsy, failure to thrive, developmental stagnation, and cortical blindness. Because of the lack of easily recognizable dysmorphism and specific neurologic manifestations, identification of patients with this condition is extremely challenging. Here we report on previously undescribed pigmentary abnormalities in 20 of 38 patients with GM3 synthase deficiency. All 20 of the patients showed freckle-like hyperpigmented macules, ranging in size from 2 to 5 mm in diameter and usually found bilaterally on the extremities, especially the dorsal aspects of the hands and feet. Seven of these patients also had depigmented macules and patches, especially on the face and extremities. These cutaneous changes were asymptomatic, and were not associated with the severity or particular phenotype of the neurologic disease. They became visible only after the first years of life with an increased incidence with advancing age. These distinct pigmentary features are not identified in 54 normal siblings, and may provide a useful clue in identifying patients with ganglioside metabolic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Epilepsy / diagnosis
  • Epilepsy / pathology*
  • Exons
  • Female
  • Genotype
  • Humans
  • Hyperpigmentation / pathology*
  • Infant
  • Male
  • Sialyltransferases / deficiency
  • Sialyltransferases / genetics
  • Skin / pathology
  • Young Adult


  • Sialyltransferases
  • haematoside synthetase

Supplementary concepts

  • Amish Infantile Epilepsy Syndrome