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

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.

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.

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.