Defining the phenotype of PGAP3-congenital disorder of glycosylation; a review of 65 cases

Mol Genet Metab. 2023 Nov;140(3):107688. doi: 10.1016/j.ymgme.2023.107688. Epub 2023 Aug 23.

Abstract

Biallelic pathogenic variants in PGAP3 cause a rare glycosylphosphatidyl-inositol biogenesis disorder, PGAP3-CDG. This multisystem condition presents with a predominantly neurological phenotype, including developmental delay, intellectual disability, seizures, and hyperphosphatemia. Here, we summarized the phenotype of sixty-five individuals including six unreported individuals from our CDG natural history study with a confirmed PGAP3-CDG diagnosis. Common additional features found in this disorder included brain malformations, behavioral abnormalities, cleft palate, and characteristic facial features. This report aims to review the genetic and metabolic findings and characterize the disease's phenotype while highlighting the necessary clinical approach to improve the management of this rare CDG.

Keywords: Alkaline phosphatase; GPI-anchor; Glycophosphatidylinositol anchor biogenesis defects; PGAP3; Psychomotor developmental delay.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple* / genetics
  • Carboxylic Ester Hydrolases / genetics
  • Congenital Disorders of Glycosylation* / diagnosis
  • Congenital Disorders of Glycosylation* / genetics
  • Glycosylation
  • Humans
  • Intellectual Disability* / genetics
  • Intellectual Disability* / pathology
  • Phenotype
  • Receptors, Cell Surface / genetics
  • Seizures

Substances

  • PGAP3 protein, human
  • Carboxylic Ester Hydrolases
  • Receptors, Cell Surface