Fat and Carbohydrate Metabolism During Exercise in Phosphoglucomutase Type 1 Deficiency

Abstract

Context:Phosphoglucomutase type 1 (PGM1) deficiency is a rare metabolic myopathy in which symptoms are provoked by exercise.Objective: Because the metabolic block is proximal to the entry of glucose into the glycolytic pathway, we hypothesized that iv glucose could improve the exercise intolerance experienced by the patient. Design:This was an experimental intervention study. Setting:The study was conducted in an exercise laboratory.Subjects: Subjects were a 37-year-old man with genetically and biochemically verified PGM1 deficiency and 6 healthy subjects.Interventions: Cycle ergometer, peak and submaximal exercise (70% of peak oxygen consumption), and exercise with an iv glucose infusion tests were performed. Main Outcome Measures:Peak work capacity and substrate metabolism during submaximal exercise with and without an iv glucose infusion were measured.Results: Peak work capacity in the patient was normal, as were increases in plasma lactate during peak and submaximal exercise. However, the heart rate decreased 11 beats minute Ϫ1 , the peak work rate increased 12.5%, and exercise was rated as being easier with glucose infusion in the patient. These results were in contrast to those in the control group, in whom no improvements occurred. In addition, the patient tended to become hypoglycemic during submaximal exercise. Conclusions:This report characterizes PGM1 deficiency as a mild metabolic myopathy that has dynamic exercise-related symptoms in common with McArdle disease but no second wind phenomenon, thus suggesting that the condition clinically resembles other partial enzymatic defects of glycolysis. However, with glucose infusion, the heart rate decreased 11 beats min Ϫ1 , the peak work rate increased 12.5%, and exercise was considered easier by the patient. (J Clin Endocrinol Metab 98: E1235-E1240, 2013)

Skeletal muscle metabolism during prolonged exercise in Pompe disease

“…Furthermore, during exercise in glycogenoses with significant blocks in muscle glycogenolytic capacity, i.e. Glycogenosis types IIIa, V, IXa and XIV, metabolism is shifted toward oxidation of fat (9,11,12), but in the present study, no compensatory increases in plasma palmitate and overall fat oxidation were seen in the patients (Fig. 4).…”

PGM1 deficiency diagnosed during an endocrine work-up of low IGF-1 mediated growth failure

“…On the other hand, functional hyperinsulinism can also occur, as observed in other CDG, such as MPI-CDG, making classical dietary treatment with complex carbohydrates (uncooked corn starch) unsuccessful. 1,3 Hypogonadotropic hypogonadism and low IGF mediated growth failure are the classic endocrine complications of disturbed glycosylation in PGM1 deficiency. Inadequate glycosylation of different glycoproteins, including gonadotrophins and their receptors, IGF-BP3 and the acid-labile subunit of insulin-like growth factor binding protein (ALS), is responsible for their impaired function.…”

Galactose supplementation in phosphoglucomutase-1 deficiency; review and outlook for a novel treatable CDG

“…Patients had exercise induced hyperammonia, decreased lactate increase during forearm ischemic tests, but no episodes of hypoglycemia, endocrine dysfunction or liver involvement (2). Glucose administration during exercise led to better exercise tolerance in this subgroup of adult PGM1 patients with primary muscle involvement (15). …”