ODP208 Hypoglycemia as a Presenting Feature of McArdle's Disease

Abstract

Abstract Introduction McArdle's disease (glycogen storage disease type V) is an autosomal recessive disease caused by mutations in the gene encoding for the muscle isoform of glycogen phosphorylase (PYGM). Characteristic symptoms include exercise intolerance, myalgia, muscle stiffness. Approximately half develop rhabdomyolysis, myoglobinuria, and renal failure. Hypoglycemia is an uncommon presenting symptom. Case report A 36-year-old male, previous college football athlete presented with jitteriness and blurry vision while exercising over the last one year. Symptoms occur 12-15 minutes into aerobic exercise. Fingerstick blood sugar during these episodes were as low as 30 mg/dl and afterwards the patient reported fatigue all day long. Consuming high carbohydrate foods and fluids supplemented with dextrose prior to exercise mitigate his symptoms. He reported no fasting hypoglycemia. Retrospectively, the patient reports that for years he noticed feeling fatigued a few minutes into starting exerice which improves after short periods of rest "second wind phenomenon." He can perform heavy resistance exercise like weightlifting but struggles with sustained aerobic activity. Past medical history is significant for HLA B27 positivity, alopecia areata and uveitis. Medications include multivitamin and creatine supplements. Physical exam revealed a healthy, well developed muscular individual with no other remarkable findings. Family history is significant for McArdle's disease in his brother, diagnosed at age 20 based on a muscle biopsy after multiple episodes of rhabdomyolysis. Grandfather had diabetes mellitus and pancreatic carcinoma. Labs revealed a creatine kinase (CK) level of 1638.7 U/L (49-397 U/L), CK-MB 49.1 ((0.1-5.9 ng/ml), 8 AM morning cortisol of 12.3 ug/dl (4.2-22.4 ug/dl), A1c 5.3%. There was no myoglobinuria. Thyroid function tests were within normal limits. Investigations done during an episode of exercise induced hypoglycemia - fingerstick blood sugar 44 mg/dl, plasma blood glucose 56 mg/dl(65-99 mg/dl), Insulin <0.5 mU/L(3-25mU/l), C-Peptide 0.5ng/ml(1.1-4.4ng/ml), Proinsulin 1.1 pmol/L(0-10. 0 pmol/L). Insulin autoantibody was negative. This ruled out exercise induced hyperinsulinemia. IGF-1 and IGF-2 levels were normal. Genetic study performed by the Glycogen Storage Disease Panel showed PYGM c.2262del (p. Lys754Asnfs*49), Pathogenic, PYGM c.1537A>G (p. Ile513Val), Uncertain Significance, PYGM c.833G>C (p. Arg278Pro), Uncertain Significance. Subsequently, the patient's brother underwent genetic testing, which confirmed the presence of all three before-mentioned PYGM variants. His father was found to carry the two variants of undetermined significance, suggesting that the patient and his brother inherited the pathogenic variant from their deceased mother. Discussion The patient's medical history, along with his personal and family's genetic findings were found to be consistent with McArdle's disease. Our patient's presentation is unique in that his exercise tolerance is much higher as compared to most individuals with McArdle's and his presenting complaint was hypoglycemia. Additionally, one of the variants of uncertain significance is likely to be recognized as pathogenic in the future. Presentation: No date and time listed