Premature Coronary Artery Disease in a Patient with Glycogen Storage Disease III

ABSTRACT: The glycogen storage diseases are a rare form of inherited metabolic disease affecting intracellular glycogen metabolism, and several studies suggest glycogen storage disease (GSD) III predisposes patients to dyslipidemia and endothelial dysfunction. The presence of premature atherosclerotic heart disease in patients with GSD III has not been reported in the literature. We report a case of a 24-year old patient with GSD III admitted with ventricular fibrillation cardiac arrest in the setting of anterior wall myocardial infarction. Further studies are warranted on the prevalence of atherosclerotic heart disease, and potential screening and preventative strategies, in this population of patients potentially at-risk for early cardiac events.

J INVASIVE CARDIOL 2010;22:E156–E158

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The glycogen storage diseases are a rare form of inherited metabolic disease affecting intracellular glycogen metabolism. Glycogen storage disease III (GSD III) (Cori’s disease) results from a deficiency in the glycogen debranching enzyme, which catalyzes the breakdown of glycogen into glucose-1-phosphate. Several studies suggest GSD III predisposes patients to dyslipidemia and endothelial dysfunction.^1–3 The presence of premature atherosclerotic heart disease in patients with GSD III has not been reported in the literature. We report a case of a 24-year old patient, with no other risk factors for coronary artery disease (CAD) than GSD III, admitted with a ventricular fibrillation cardiac arrest in the setting of anterior wall myocardial infarction. Case Report. The patient is a 24-year old man with history of GSD IIIb who was in good general health and worked out regularly. He did not have diabetes, hypertension, family history of coronary disease, or a significant smoking history. He was admitted after a witnessed cardiac arrest, and was without bystander CPR for 6 minutes. On arrival by EMS he was found to be in ventricular fibrillation and subsequently defibrillated in the field with 150J by EMS. He was intubated and started on a dopamine drip. In the ER his blood pressure was 133/81 and HR 86. On neurological exam he was unresponsive to painful stimuli, and his pupils were 6mm and sluggishly reactive. He had a left forehead laceration. The remainder of his physical exam was unremarkable. His ECG revealed Q waves in V1-V3, with 3 mm J-point elevation in V3 only. Given concern for possible CNS trauma, the patient underwent CT of the head and neck, which was initially thought to show subluxation of C3-4. There was no CNS bleed. Initial cardiac biomarkers were negative; creatinine was found to be elevated at 1.8 mg/dl. Transthoracic echocardiogram revealed normal LV size and wall thickness, apical akinesis and anterior hypokinesis, and LVEF 35%. The patient was maintained on induced hypothermia for 24 hours. Serial cardiac enzymes increased over the first 24 hours, with a troponin of 34. Repeat CT of the head and neck was without evidence for the prior visualized subluxation, and no hemorrhage. Coronary angiography performed within 24 hours of admission, during induced hypothermia, revealed an 80% mid-LAD stenosis without occlusion. There were significant intimal irregularities with long areas of moderate stenosis in the circumflex and right coronary arteries. Coronary spasm, dissection, or coronary atherosclerosis were all considered possible mechanisms for his infarct. The patient was started on medical therapy for acute coronary syndrome with aspirin, enoxaparin, clopidogrel, and atorvastatin. Repeat TTE revealed a further decline in LV function to LVEF 25%. On hospital day #3 the patient’s mental status improved and he was extubated. Given the significant multivessel narrowing seen on initial coronary angiography, the decision was made to perform repeat coronary angiography on hospital day #5. On this study, during which the patient was euthermic, the moderate stenoses seen in the right and left circumflex coronary arteries had resolved; these were presumably caused by transient coronary vasospasm or possibly related to hypothermia. The mid-LAD atherosclerotic plaque was confirmed on repeat angiography, and intravascular ultrasound of the LAD lesion revealed a large atherosclerotic burden with a residual luminal area of 5 mm2. In light of the residual luminal area, the lesion was not felt to be hemodynamically significant and no percutaneous coronary intervention was performed. The patient was placed on optimal medical therapy for coronary artery disease and reduced LV systolic function. Treatment for dyslipidemia was initiated with atorvastatin and niacin. The patient was without symptoms and was discharged home on hospital day #11. He was doing well at 1-month follow-up, having made a full neurologic recovery. Repeat transthoracic echocardiogram at one month revealed significant improvement in LV systolic function with LVEF of 60%. His lipid panel during hospital admission revealed total cholesterol 128 mg/dl, triglycerides 164 mg/dl, HDL 24 mg/dl, LDL 71 mg/dl. Review of his childhood labs at 2 years of age was notable for total cholesterol 228 mg/dl, triglycerides 204 mg/dl, AST 193 IU/L, ALT 330 IU/L, alkaline phosphatase 510 IU/L, total bilirubin 0.4 mg/dl, total protein 7.3 g/dl and albumin 4.5 g/dl. Subsequent lipid panel at age 16 demonstrated a total cholesterol 211, HDL 34, LDL 136, and triglycerides 203. Discussion. The glycogen storage diseases are a group of disorders of glycogen synthesis and breakdown. GSD III, or Cori’s disease, is an autosomal recessive deficiency of the glycogen debranching enzyme, located on chromosome 1q21. Glycogen debranching enzyme normally catalyzes the breakdown of glycogen to glucose-1-phosphate. Deficiency, or in some cases, absence, of glycogen debranching enzyme activity results in abnormal glycogen buildup, in the form of the partially catabolized “limit dextrin,” in affected tissues. GSD IIIa, IIIc, and IIId affect both liver and muscle, while GSD IIIb involves only liver. The diagnosis of GSD IIIb is typically made in childhood when patients present with hepatomegaly and hypoglycemia. There is no specific treatment available, and the management of these patients is focused on the avoidance of hypoglycemia with frequent feedings with branched carbohydrates (such as corn starch) overnight. Symptoms of hypoglycemia typically improve as the child ages. Complications of liver involvement include fibrosis, hepatic adenomas, hepatocellular carcinoma, and rarely cirrhosis. GSD IIIa and IIIb have been shown to be associated with hyperlipidemia related to increased circulating free fatty acids. Additionally, GSD III has been shown to be associated with endothelial dysfunction. Patients with GSD III and muscle involvement may develop left ventricular hypertrophy related to intramyocardial glycogen deposition, which may be a focus for development of reentrant dysrhythmias . There have been case reports of sudden cardiac death in the setting of GSD III-related cardiomyopathy.^4,5 The finding of hyperlipidemia and endothelial dysfunction in young patients with GSD III suggests that these patients are at risk for premature atherosclerotic disease. To our knowledge this is the first case documenting premature atherosclerosis in a patient with GSD III. He had no other significant risk factors for having substantial coronary atherosclerosis at his age. Further studies are warranted to evaluate the incidence of early atherosclerotic heart disease in patients with GSD III who survive to adulthood. If patients with GSD III have an increased prevalence of coronary disease at a young age, then screening and preventative strategies will need to be considered. Conclusions. GSD III is a rare disorder of glycogen metabolism that is known to predispose patients to dyslipidemia and endothelial dysfunction. We report a case of premature atherosclerosis related to GSD III. Further studies investigating the prevalence of coronary disease in patients with GSD III are warranted.

References

1. Bernier AV, Centner CP, Correia CE, et al. Hyperlipidemia in glycogen storage disease type III: Effect of age and metabolic control. J Inherited Metabolic Dis 2008;31:729–732. 2. Yekelar E, Dursun M, Emeksiz E, et al. Prediction of premature atherosclerosis by endothelial dysfunction and increased intima-media thickness in glycogen storage disease types Ia and III. Turkish J Pediatrics 2007;49;115–119. 3. Bernier AV, Correia CE, Haller MJ, et al. Vascular dysfunction in glycogen storage disease type I. J Pediatrics 2009;154;588–591. 4. Tada H, Kurita T, Ohe T, et al. Glycogen storage disease type III associated with ventricular tachycardia. Am Heart J 1995;130;911–912. 5. Akazawa H, Kuroda T, Kim S, et al. Specific heart muscle disease associated with glycogen storage disease type III: Clinical similarity to the dilated phase of hypertrophic cardiomyopathy. Eur Heart J 1997;18:532–533.

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From the Department of Cardiology, California Pacific Medical Center, San Francisco, California. The authors report no conflicts of interest regarding the content herein. Manuscript submitted November 6, 2009, provisional acceptance given January 11, 2010, final version accepted February 2, 2010. Address for correspondence: Gary Milechman, MD, FACC, Department of Cardiology, California Pacific Medical Center, 2333 Buchanan Street, San Francisco, CA 94115. Email: MilechG@sutterhealth.org