PGM3-congenital disorder of glycosylation – PGM3 gene

Congenital alteration of PGM3 glycosylation, also known as AGM1 deficiency or N-acetylglucosamine phosphate mutase 1 deficiency, is a hereditary process of variable severity and symptomatology that primarily affects the immune system, but which can also affect other areas of the organism.

Signs and symptoms related to this process may include immune deficiency, or an impaired function of the bone marrow that can lead to a decrease in the production of all blood cells; allergies, asthma or inflammatory skin conditions such as eczema; autoimmune processes; and abnormally high concentrations of immunoglobulins, particularly immunoglobulin E (IgE); Other signs may include intellectual disability; developmental delay; hypotonia; skeletal abnormalities that involve the ribs or bones in the hands, feet or spine; different facial features, such as hypoplasia of the middle face, micrognathia, fleshy lips, corners of the mouth down and wide nostrils open forward instead of down. In addition, affected individuals may suffer from lung, gastrointestinal and kidney problems.

This process is due to mutations in the PGM3 gene (phosphoglucomutase 3), located on the long arm of chromosome 6 (6q14.1), which encodes the enzyme phosphoglucomutase 3 (PGM3). This enzyme is involved in glycosylation. Glycosylation modifies proteins and lipids so they can perform a wider variety of functions. The PGM3 enzyme converts N-acetylglucosamine-6-phosphate into N-acetylglucosamine-1-phosphate. This conversion is necessary to produce uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), which is necessary to transfer sugars to the growing oligosaccharides during glycosylation.

At least 16 mutations in the PGM3 gene have been described that give rise to the development of congenital alteration of PGM3 glycosylation. The identified mutations result in the synthesis of an enzyme with reduced activity. Without an enzyme that works properly, there is a deficiency of UDP-GlcNAc and glycosylation cannot proceed normally. The wide variety of signs and symptoms in PGM3-CDG is probably due to an alteration of the glycosylation of proteins and lipids that are necessary for the normal function of many organs and tissues. Immune system proteins rely heavily on glycosylation to function normally, which probably explains why people with PGM3-CDG have immune deficiency.

This disease is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI we detect mutations associated with congenital alteration of PGM3 glycosylation, by complete PCR amplification of exons of the PGM3 gene, and subsequent sequencing.

Recommended samples: blood taken with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).