PGM1-CDG

Other Names: GSD type 14; GSDXIV; Phosphoglucomutase deficiency type 1; Type 14 glycogenosis; Congenital disorder of glycosylation, type It ; CDG syndrome type It; CDG-It; CDG1T; Congenital disorder of glycosylation type 1t; Congenital disorder of glycosylation type It; Phosphoglucomutase-1 deficiency; PGM1-related congenital disorder of glycosylation; Glycogen storage disease due to phosphoglucomutase deficiency

PGM1-CDG is one of the many subtypes of congenital disorders of glycosylation (CDG), which are inherited diseases that affect the body's process of adding sugar building blocks to proteins (glycosylation).There are many steps in glycosylation, each of which is controlled by a different gene. The type of CDG a person has depends on which gene is involved.

Cause

PGM1-CDG is caused by mutations in the PGM1 gene.Phosphoglucomutase-1 is an enzyme that in humans is encoded by the PGM1 gene. The protein encoded by this gene is an isozyme of phosphoglucomutase (PGM) and belongs to the phosphohexose mutase family. There are several PGM isozymes, which are encoded by different genes and catalyze the transfer of phosphate between the 1 and 6 positions of glucose. In most cell types, this PGM isozyme is predominant, representing about 90% of total PGM activity. In red blood cells, PGM2 is a major isozyme. This gene is highly polymorphic.

Inheritance

Autosomal recessive inheritance, a 25% chance

It is inherited in an autosomal recessive manner.

Signs and symptoms

The signs and symptoms of PGM1-CDG can be different from person to person. They may include cleft palate or bifid uvula; low blood sugar (hypoglycemia); endocrine disorders; muscle disease, leading to muscle weakness or death of muscle fibers (rhabdomyolysis); liver disease; blood clotting problems; and a weak and enlarged heart chamber (dilated cardiomyopathy).Some people with PGM1-CDG have central nervous system involvement such as seizures, development delay, or intellectual disability.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 5%-29% of people have these symptoms

• Cerebral venous thrombosis(Blood clot in cerebral vein)
• Dyspnea(Trouble breathing)
• Elevated serum creatine kinase(Elevated blood creatine phosphokinase)
• Fatigue(Tired)
• Micrognathia(Little lower jaw)
• Pierre-Robin sequence
• Reduced antithrombin III activity
• Rhabdomyolysis(Breakdown of skeletal muscle)

Diagnosis

The diagnosis may be suspected based on symptoms and specific blood test results, and it is confirmed with genetic testing.

Treatment

Treatment depends on the symptoms and severity in each person and may include oral D-galactose supplementation, standard treatment of hypoglycemia, and/or heart medications or heart transplantation for cardiomyopathy. The course of the disorder and whether symptoms or complications may affect the lifespan are difficult to predict and vary among people with PGM1-CDG.

NIH genetic and rare disease info

• NIH info on PGM1-CDG

PGM1-CDG is a rare disease.