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McArdle disease presenting as acute renal failure.

Abstract: In 1951, McArdle described a glycogen storage disorder which presents primarily as a myopathy. It is characterized by muscle pain, weakness and exercise intolerance with elevated creatine kinase from rhabdomyolysis. The pathophysiology involves a deficiency of myophosphorylase enzyme resulting in an inability to degrade glycogen stores. We present a novel case of McArdle disease (glycogen storage disease V [GSDV]) in a patient who had sickle cell trait and bulimia. The disease went unrecognized despite several admissions to the hospital with increased creatine kinase and muscle myopathy until the patient's initial presentation with acute renal failure.

Key Words: McArdle disease, glycogen storage disease V, GSDV, sickle cell trait, bulimia


In 1951, McArdle reported on a myopathy caused by myophosphorylase deficiency, an enzyme which breaks down muscle glycogen during exercise. (1) Since then several cases of McArdle disease have been reported with different presentations. We present a case of McArdle disease with sickle cell trait and bulimia presenting as acute renal failure.

Case Report

A 20-year-old African-American female with sickle cell trait was admitted with generalized muscle aches associated with nausea and vomiting for six hours. The patient had gone dancing and had quickly developed muscle aches. She reported mild body aches and a headache during the previous week after moving furniture. The patient presented with excruciating muscle pain throughout her body and would not let the examiner test her range of motion in her extremities.

She had several admissions to the hospital in the past, with essentially the same complaints. She had elevated serum creatine kinase (CK) levels on each visit and her symptoms resolved with hydration and symptomatic management. Her muscle aches, body pains and increased creatine kinase levels were attributed to sickle cell trait and further investigations were never pursued. Her mother also had a history of muscle aches on heavy physical activity but her symptoms were never severe enough to be hospitalized. The patient denied any history of drug abuse. She had a significant past medical history which included depression, posttraumatic stress disorder (PTSD), bulimia and asthma. Her medication list included albuterol, ibuprofen and folic acid.

On physical examination, the patient was found to be lying on the bed with pain and tenderness all over her body. All four extremities were extremely tender to touch. Soft tissue swelling was noted on the thighs bilaterally with the left thigh swollen more than the right. No rash was seen on the skin. The rest of the physical examination was essentially normal. Her vitals showed a temperature of 96.5[degrees]F, heart rate was tachycardic at 126 beats per minute, respiratory rate was 28/min, oxygen saturation was 99% on room air and blood pressure was 135/89 mm Hg. Initial labs revealed a sodium of 135 mmol/L, potassium 4.2 mmol/L, chloride 106 mmol/L, bicarbonate 22 mmol/L, BUN 11 mg/dL, creatinine 1.1 mg/dL, blood sugar 123 mg/dL, and calcium 9 mg/dL. Reticulocyte count was 1.4%. WBC was 9.3/[mm.sup.3], hemoglobin 16.6 g/dL, hematocrit 46.3%, platelets 436/[mm.sup.3]. Urinalysis showed large blood with 10 to 25 RBCs, positive myoglobin and 10 to 25 WBC with 1+ bacteria, positive nitrites and negative leukocyte esterase. Liver function tests revealed an albumin of 2.9 g/dL, total bilirubin 0.7 mg/dL, alkaline phosphatase of 70 U/L, AST 1391 U/L (15-41 U/L), and ALT of 292 U/L (14-54 U/L). Initial serum creatine kinase was 515,507 U/L (38-234 U/L). Lactic acid was 7604 U/L. Amylase and lipase levels were within normal limits. Urine drug screen was positive for opiates secondary to morphine given in the emergency room for pain.

The patient was admitted to the intensive care unit (ICU) and vigorous hydration was initiated with one quarter normal saline and sodium bicarbonate. However, her creatinine continued to rise and nephrology was consulted. Compartment syndrome was ruled out after measuring compartment pressures. TSH and ANA were both ordered to evaluate elevated serum CK levels. TSH was 0.7 mIU/mL. ANA was negative. Hematology/oncology was consulted regarding rhabdomyolysis from sickle cell trait. They opined that rhabdomyolysis associated with sickle cell trait is only seen with vigorous activity or in high altitude regions. Neither was the scenario in this case. An underlying vasculitic process was considered and anti-JO and SRP were tested which were negative. Cardiolipin antibodies were nonsignificant and CRP was 5.1 mg/dL. Meanwhile, the patient's renal function worsened with oliguria. A Lasix drip was initiated because of volume overload. After seven days of hospitalization, hemodialysis was initiated with declining renal function. At that point, a metabolic myopathy was entertained as a cause for the patient's rhabdomyolysis. However, ischemic forearm exercise stress test to diagnose metabolic myopathy could not be performed as the patient was not cooperative. Finally, a muscle biopsy of the right quadriceps was performed and was sent to a pathology lab in Texas. After two sessions of hemodialysis, the patient improved clinically and became pain free. Her serum CK level gradually dropped along with serum transaminases derived from the muscle. Her kidney function improved gradually and she did not require further dialysis. Her biopsy revealed multifocal rhabdomyolysis with myofiber necrosis and absence of phosphorylase staining consistent with McArdle disease (type V glycogenosis) (Fig. 1).

Following the diagnosis, a nutritionist was consulted, who stated that diet had no role in the patient's McArdle disease. With her history of bulimia, psychiatry was consulted, as hypokalemia and hypophosphatemia are both known to precipitate rhabdomyolysis. The patient was educated about her diagnosis and was told not to undertake heavy physical activity or induce vomiting. The patient was discharged with a creatine kinase of 829 U/L and resolution of her symptoms (Fig. 2).

Biopsy findings revealed sections of snap frozen and paraffin-embedded skeletal muscle from the quadriceps with randomly distributed individual fiber necrosis and reactive inflammatory changes including some apparent myophagocytosis. No vasculitis was seen. Apart from the small lymphocytic aggregates and histiocytic cells which were present, there was no perifascicular atrophy or significant vacuolar change. The peripheral nerve trunk present in the frozen material showed no inflammatory infiltrate or definitive neuropathy. Staining with modified trichrome stain showed normal endomysial connective tissue with no ragged red fibers, nemaline rods, or central cores. The individual fiber necrosis and phagocytosis were dramatically demonstrated with this stain. With ATPase stains at pH 9.4 and 4.5, there was mild type 2 fiber atrophy. Affected fibers were of both fiber types among those undergoing myophagocytosis.

Alkaline phosphatase stain highlighted the extensive regeneration of individual fibers.

There was normal staining with cytochrome C oxidase. Staining with phosphorylase stain showed no activity, establishing the diagnosis of McArdle disease, as seen in Figure 3 and Figure 4.


McArdle disease is caused by myophosphorylase deficiency, an enzyme which breaks down muscle glycogen during exercise. Since then, several cases have been reported with different presentations. McArdle disease is inherited as an autosomal recessive disorder and the gene for myophosphorylase is located on band llq13. The patient's mother reported that she also developed muscle cramps with exercise but they were never severe enough to be hospitalized.



The fatal infantile form presents with hypotonia and diminished deep tendon reflexes. (2) The late onset form has a similar clinical presentation to the early onset with exercise intolerance, cramps, and myoglobinuria. Some patients have fixed proximal limb and bulbar weakness. (3) Several other presentations include an asymmetric, late onset arm weakness (4) and unexplained dyspnea which is believed to be due to respiratory muscle fatigue. (5) McArdle disease has also been diagnosed following statin-induced myositis, (6) hypercreatine kinasemia during febrile episodes in a 1-year-old (7) and also with rhabdomyolysis seen after an acute asthmatic attack in a 1-year-old. (8)

Rhabdomyolysis leads to muscle necrosis and myoglobinuria, which subsequently may lead to acute renal failure. (10) The incidence rate of rhabdomyolysis leading to renal failure in McArdle disease has not been reported. In the general population, it is 30%. (11) Aggressive hydration with alkaline diuresis is indicated in myoglobinuria resulting from rhabdomyolysis. Care should be taken to protect the kidneys to prevent the need for dialysis. If renal failure develops, dialysis should be initiated.



Our case was also complicated by the fact that our patient carried a diagnosis of bulimia. Bulimia can induce electrolyte changes in the body like hypokalemia and hypophosphatemia which could also precipitate rhabdomyolysis. To our knowledge, there has been no case reported in the literature of McArdle disease presenting in a patient with both sickle cell trait and bulimia, both of which can precipitate rhabdomyolysis. The fact that our patient had bulimia is also important from the treatment perspective. This is because bulimia can precipitate rhabdomyolysis in a patient with McArdle disease who is already predisposed to it.


There is no effective treatment for McArdle disease as yet; however, several different treatment trials have been reported. High protein diet, (12) sucrose diet, (13) supplementation of vitamin [B.sub.6] (14) or oral creatinine (1) and gene replacement therapies (15) have all been studied, but there is no definitive answer yet. Moderate physical activity seems to be the best treatment for now. (16) It helps increase exercise tolerance, and circulation to the muscles, thereby providing increased glucose and free fatty acids to the muscle. It also increases the amount of mitochondria in the muscles necessary for oxidative phosphorylation. Patients should be educated to avoid a sedentary lifestyle, as this increases weight, decreases cardiovascular capacity and decreases effort tolerance. (17) In addition, patients should avoid isometric and sustained dynamic exercises.


Elevated creatine kinase levels should never be ignored, especially if patients present with repeated episodes. In rare diseases like McArdle, the only presenting sign may be this elevated serum marker. Sickle cell trait can cause CK elevation, although this only occurs at high altitudes or in circumstances of extreme exertion. Bulimia is a predisposing factor for rhabdomyolysis by causing electrolyte disturbances such as hypokalemia and hypomagnesemia. Internists should meticulously consider all contributing factors to an elevated CK level and should be able to establish a definitive diagnosis in time to prevent complications like acute renal failure.


The authors wish to thank Dr. Thomas Crouch for his valuable input into the patient's diagnosis and Dr. Christopher Mullen and his team for their excellent patient care.


1. Haller RG. Treatment of McArdle disease. Arch Neurol 2000;57:923-924.

2. DiMauro S, Hartlage PL. Fatal infantile form of muscle phosphorylase deficiency. Neurology 1978;28:1124-1129.

3. Pourmand R, Sanders DB, Corwin HM. Late-onset McArdle's disease with unusual electromyographic findings. Arch Neurol 1983;40:374-377.

4. Wolfe GI, Baker NS, Haller RG, et al. Barohn McArdle's disease presenting with asymmetric, late-onset arm weakness. Muscle Nerve 2000;23:641-645.

5. Voduc N, Webb KA, D'Arsigny C, et al. McArdle's disease presenting as unexplained dyspnea in a young woman. Can Respir J 2004;11:163-167.

6. Livingstone C, Al Riyami S, Wilkins P, Ferns GA. McArdle's disease diagnosed following statin-induced myositis. Ann Clin Biochem 2004;41:338-340.

7. Ito Y, Saito K, Shishikura K, et al. A 1-year-old infant with McArdle disease associated with hyper-creatine kinase-emia during febrile episodes. Brain Dev 2003;25:438-441.

8. Tsushima K, Koyama S, Ueno M, et al. Rhabdomyolysis triggered by an asthmatic attack in a patient with McArdle disease. Intern Med 2001;40:131-134.

9. Dincer HE, Raza T. Compartment syndrome and fatal rhabdomyolysis in sickle cell trait. WMJ 2005;104:67-71.

10. Grunfeld JP, Ganeval D, Chanard J, et al. Acute renal failure in McArdle's disease: report of two cases. N Engl J Med 1972;286:1237-1241.

11. Saad EB. Rhabdomyolysis and Myoglobinuria. 1997. Available at Accessed January 6, 2007.

12. Slonim A, Goans PJ. Myopathy in McArdle's syndrome: improvement with a high-protein diet. N Engl J Med 1985;312:355-359.

13. Vissing J, Haller RG. The effect of oral sucrose on exercise tolerance in patients with McArdle's disease. N Engl J Med 2003;349:2503-2509.

14. Beynon RJ, Bartram C, Hopkins P, et al. McArdle's disease: molecular genetics and metabolic consequences of the phenotype. Muscle Nerve 1995;3:S18-S22.

15. Pari G, Shoubridge E, Crerar MM, et al. In vitro and in vivo adenovirus-mediated gene transfer in myophosphorylase deficiency Ann Neurol 1998;44:989.

16. Ollivier K, Hogrel JY, Gomez-Merino D, et al. Exercise tolerance and daily life in McArdle's disease. Muscle Nerve 2005;31:637-641.

17. Lewis SF, Haller RG. The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue. J Appl Physiol 1986;61:391-401.
Problems and obstacles offer a chance for reflection that otherwise
would be precluded by the swift routine of life.
--Thomas Moore

Jayasree Pillarisetti, MD, and Awad Ahmed, DO

From the University of Missouri, Kansas City School of Medicine, Kansas City, MO.

Reprint requests to Dr. Jayasree Pillarisetti, 4262 Jefferson Street, #8407, Kansas City, MO 64111. Email:

Accepted June 29, 2006.


* Elevated creatine kinase levels should never be ignored, especially if the patient presents with repeated episodes.

* Sickle cell trait can cause creatine kinase elevation, although this only occurs at high altitudes or in circumstances of extreme exertion.

* Bulimia is a predisposing factor for rhabdomyolysis by causing electrolyte disturbances such as hypokalemia and hypomagnesemia.
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Title Annotation:Case Report
Author:Ahmed, Awad
Publication:Southern Medical Journal
Date:Mar 1, 2007
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