Whole exome sequencing of the patient revealed compound heterozygous mutations of PMM2: c.580C>T (p.Arg194*) and c.713G>C (p.Arg238Pro) which mutations were associated with congenital disorder of glycosylation Ia (CDG-Ia: PMM2-CDG).
Congenital disorder of glycosylation Ia (CDGIa) is an autosomal recessive disease that is caused by mutations in the gene PMM2 encoding phosphomannomutase, an enzyme that synthesizes mannose-1-phosphate, an important intermediate for the N-glycan biosynthesis.
Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1 or Jaeken syndrome) is the prototype of a class of genetic multisystem disorders characterized by defective glycosylation of glycoconjugates.
29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype.
International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up.
In addition, the classical screening test, serum transferrin isoelectrofocusing, is only positive in about 60% of CDG, and can even become negative in some CDG particularly in PMM2-CDG, the most frequent N-glycosylation defect.
We distinguish two main groups: on the one hand, the CDG types with predominant or isolated liver involvement including MPI-CDG, TMEM199-CDG, CCDC115-CDG, and ATP6AP1-CDG, and on the other hand, the CDG types associated with liver disease but not as a striking, unique or predominant feature, including PMM2-CDG, ALG1-CDG, ALG3-CDG, ALG6-CDG, ALG8-CDG, ALG9-CDG, PGM1-CDG, and COG-CDG.
Congenital disorders of glycosylation type Ia (CDG-Ia) is a recessive metabolic disorder caused by mutations in the PMM2 gene and characterized by a defect in the synthesis of N-glycans.
Some of these conditions, including PMM2-CDG, frequently present with recognizable skin abnormalities such as abnormal fat distribution, skin wrinkling, or peau d'orange, whereas others, such as COG7-CDG and ATP6V0A2-CDG, have been described in association with cutis laxa: wrinkled, inelastic, and sagging skin.
We studied 29 patients with the 2 most prevalent types of type I CDG, ALG6 (asparagine-linked glycosylation protein 6)-deficiency CDG and PMM2 (phosphomannomutase 2)-deficiency CDG, and 23 first- and second-degree relatives with a heterozygous mutation and measured plasma cholesterol levels.