Deficiency in phosphoglucomutase 1

(glycogenosis XIV, hypoglycosylation of serum glycoproteins)

Extremely rare. :Autosomal recessive transmission of a mutation of the PGM1 gene coding for phosphoglucomutase1 that catalyzes the interconversion of glucose 1-phosphate and glucose-6-phosphate.

Glucose-1-phosphate is an important intermediate metabolite:

- in the homeostasis of glucose: glucose-1-phosphate is a product of the degradation of glycogen in case of hypoglycemia, but also serves for glycogen synthesis and glycosylation of glycoproteins, and glucose-6-phosphate is a direct source of energy and lactates.

- in the N-glycosylation of the glycoproteins at the level of the endoplasmic reticulum.

The clinical presentation is variable:

- at birth: bifid uvula with or without cleft palate

- hypoglycemia and lactic acidosis: need for frequent meals, nocturnal gavage

- signs of liver disease: elevated GPT, steatosis, fibrosis

- dilated cardiomyopathy

- signs of myopathy with high CPK levels, intolerance to muscular effort with rhabdomyolysis; 2 undocumented cases of malignant hyperthermia during general anesthesia

- growth retardation (size < P5)

- hypogonadotropic hypogonadism

Treatment with high doses of oral lactose or galactose seems to fix some of these anomalies.

Anesthetic implications:

infusion of glucose with electrolytes as soon as the preoperative fasting period is started; monitor blood glucose levels; given the muscular involvement and the risk of rhabdomyolysis, there is probably a significant risk of rhabdomyolysis associated with anesthesia: avoid succinylcholine, halogenated agents and tourniquets.

References :

Stojkovic T, Vissing J, Petit F, Piraud M et al.
Muscle glycogenosis due to phosphoglucomutase 1 deficiency.
NEJM 2009; 361:425-7.
Tegtmeyer LC, Rust S, van Scherpenzeel M, Ng BG, Losfeld M-E et al.
Multiple phenotypes in phosphoglucomutase 1 deficiency.
NEJM 2014; 370: 533-42 et correspondance NEJM 2014: 370(21): 2051-2

Updated: September 2019