MAN1B-CDG: Novel variants with a distinct phenotype and review of literature

Eur J Med Genet. 2019 Feb;62(2):109-114. doi: 10.1016/j.ejmg.2018.06.011. Epub 2018 Jun 14.


Background: Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases due to impaired lipid and protein glycosylation. It comprises a characteristic high frequency of intellectual disability (ID) and a wide range of clinical phenotypes.

Objective: To identify the underlying diagnosis in two families each with two siblings with variable level of ID through trio whole exome sequencing.

Methods: Both the families were recruited to the Deciphering Developmental Disorders (DDD) study to identify the aetiology for their ID. Further work-up included isoelectric focusing (IEF) of serum transferrin done to add evidence to the molecular diagnosis.

Results: These patients were found to have three novel variants in MAN1B1 inherited from their healthy parents. Serum transferrin IEF showed a type 2 pattern.

Discussion: MAN1B1 variants were initially described in association with non-syndromic ID; subsequent literature suggested that variants in MAN1B1 resulted in a CDG-type II syndrome. However, there remains a paucity of literature on detailed clinical phenotyping and it still remains a rare form of CDG. The present patients showed the phenotype previously reported in MAN1B1-CDG: a characteristic facial dysmorphism, hypotonia, truncal obesity and in some, behavioural problems.

Conclusions: In unexplained ID, serum transferrin should be included in the first-line screening. With advances in genomic medicine, it is important to diagnose CDG as this has implications for management and recurrence risk counselling.

Keywords: Glycosylation; Intellectual disability; Obesity; Syndromal; Transferrins.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child
  • Congenital Disorders of Glycosylation / genetics*
  • Congenital Disorders of Glycosylation / pathology
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Female
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Phenotype*
  • Syndrome
  • alpha-Mannosidase / genetics*


  • alpha-Mannosidase