Congenital disorder of glycosylation type 1a (PMM2-CDG)

It belongs to a group of autosomal recessive diseases affecting enzymes involved in the synthesis of glycoproteins. They mainly affect the central and peripheral nervous system, but also other systems.

Congenital disorders of glycosylation are inborn errors of metabolism characterized by defective activity of enzymes involved in glycosylation processes (modification of proteins and other macromolecules by addition and processing of oligosaccharide side chains). The most common of these is congenital glycosylation disorder type 1a caused by a deficiency of the enzyme phosphomannomutase 2 and which is inherited in an autosomal recessive pattern.

It is estimated that this disorder has a frequency in the general population of between 1 case per 50,000-100,000 individuals.

Symptoms

Three groups are distinguished according to the clinical and severity of the symptoms, the infantile form, the late infantile form and the adult form. The infantile form is the most severe and develops after birth, in which axial hypotonicity, hyporeflexia, strabismus and developmental delay are observed. Symptoms can be very severe and there are cases with severe neurological damage in which patients do not survive more than one year. Cerebellar hypoplasia, hepatomegaly and retinitis pigmentosa may occur.

In the late infantile form (onset between 3-10 years of age), hypotonia, ataxia, delayed motor and language development, seizures, retinitis pigmentosa and skeletal abnormalities occur.

When symptoms develop in adulthood, they are usually less severe, peripheral neuropathy and retinitis pigmentosa occur. Skeletal alterations and premature aging, defects in the development of the gonads such as hypogonadism and increased risk of deep vein thrombosis have also been observed.

Disease management

Treatment of patients with congenital glycosylation disorder is symptomatic. In the severe infantile form it includes care to ensure caloric intake (use of nasogastric tube or gastrostomy tube). Standard treatment for seizures. Follow-up by a multidisciplinary team including hematologists, immunologists, nephrologists, ophthalmologists, ophthalmologists, physiotherapists and speech therapists is required.

Genes analyzed

PMM2

Bibliography

Andreotti G, Pedone E, Giordano A, et al. Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation. Mol Genet Genomic Med. 2013 May;1(1):32-44.

Altassan R, Péanne R, Jaeken J, et al. International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: diagnosis, treatment and follow up. J Inherit Metab Dis. 2019 Jan;42(1):5-28.

Lam C, Krasnewich DM. PMM2-CDG. 2005 Aug 15 [updated 2021 May 20]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.

Haven't you taken a DNA test yet?

Get your genetic test and find out all about yourself.

starter
Starter DNA test

Ancestry, Traits and Wellness

Buy
starter
Advanced DNA test

Health, Ancestry, Traits and Wellness

Buy
Father's Month Only until 20 June on our DNA tests. Use our code DAD15
Buy