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Fenofibrate Therapy in Carnitine Palmitoyl Transferase-2 Deficiency Improves Beta-oxidation of Fatty Acids But Does Not Prevent Rhabdomyolysis
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Abstracts CSANZ Abstracts 2011
Heart, Lung and Circulation 2011;20S:S1–S155
ABSTRACTS
128 Australian Experience with LDL-apheresis for the Treatment of Severe Autosomal Dominant Hypercholesterolaemia (ADH)
130 Fenofibrate Therapy in Carnitine Palmitoyl Transferase2 Deficiency Improves Beta-oxidation of Fatty Acids But Does Not Prevent Rhabdomyolysis
M. Page 1,2,∗ , J. Burnett 1,2,3 , F. van Bockxmeer 3,4 , L. Southwell 1 , J. Gerace 5 , P. Cannell 5 , G. Watts 1,2
M. Yudi ∗ , I. Hamilton-Craig, A. Wright
1 Lipid
Disorders Clinic, Royal Perth Hospital, Perth, Australia 2 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia 3 Core Clinical Pathology and Biochemistry, Royal Perth Hospital, Perth, Australia 4 School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia 5 Haematology, Royal Perth Hospital, Perth, Australia Introduction: Low density lipoprotein (LDL)-apheresis offers radical therapy for severe or refractory dyslipidaemias. We have employed this treatment at Royal Perth Hospital since 2003 and herewith present our experience with the first cases of ADH. Methods: Retrospective review of hospital records and patient interviews: data extracted related to demographic, clinical and genetic status, laboratory and imaging findings, and LDL-apheresis procedures. Results: Three patients (Patient 1, female, aged 40 years at commencement; Patient 2, female, 34 years; Patient 3, female, 14 years) had homozygous ADH (compound heterozygous for mutations in the LDLR gene). Patient 4 had drug-intolerant, heterozygous familial defective apoB (due to a mutation in the APOB gene). LDL-apheresis was performed by cascade filtration, once every one to four weeks. 333 procedures were performed since 2003. Pretreatment LDL-cholesterol was 10.5 ± 4.6 mmol/L (range 7.1–16.9). The homozygous patients continued on maximal cholesterol-lowering drug therapy. Mean acute lowering of LDL-cholesterol with each procedure was 71.5 ± 11.9% (P = 0.002); long-term time-averaged lowering was 40.3 ± 22.7% (P = 0.003). There were also reductions in triglyceride, apoB and Lp(a). Serial ultrasonography of carotid arteries and Achilles tendons, and coronary angiography were consistent with stabilisation/regression of lesions. All patients remained clinically stable. Problems encountered included iron deficiency anaemia and minor reactions to a particular batch of filtration columns. The mean annual cost per patient was $30,688 (2010 prices). Conclusion: LDL-apheresis by cascade filtration is a safe, effective and well-tolerated treatment for severe hypercholesterolaemia and should be incorporated in clinical services for patients with ADH. doi:10.1016/j.hlc.2011.05.131 129 This abstract has been withdrawn.
Gold Coast Hospital, Australia Background: Carnitine palmitoyl transferase-2 (CTP2) deficiency is an autosomal recessive trait manifest in the adult by recurrent episodes of rhabdomyolysis, often precipitated by dehydration, heat exposure or vigorous exercise. CTP-2 deficiency results in defective transport of long-chain fatty acids across the mitochondrial membranes into the cytosol for beta-oxidation, resulting in defective ATP generation for normal muscular contraction and structural integrity. Fibrate therapy has been used to improve clinical and biochemical sequelae of CTP-2 deficiency. Case: A man with CTP-2 deficiency, diagnosed at age 19 years when rhabdomyolysis was precipitated by vigorous exercise, presented at age 59 years for management of hypercholesterolaemia. He had a five-year history of hypertension, controlled with lisinopril therapy, and a malignant melanoma was removed 10 years previously. He was intolerant of statin therapy because of myalgia. Fenofibrate 145 mg/day was commenced and plasma fatty acid profiles determined prior to and after six months of therapy. Plasma palmitoyl- and oleoylcarnitine levels improved, consistent with improved fatty acid beta-oxidation and CTP-2 activity. Myalgia and muscle cramping also improved. Three months later, while trekking in Fiji in temperatures >38 ◦ C he developed severe myalgia, weakness, fatigue and fever and presented to hospital in acute renal failure [creatinine 167 mol/L (RR < 108), CK 44,100 U/L (RR < 171)]. With fluid resuscitation he recovered without dialysis. Fenofibrate therapy was discontinued, with return of lipid profile towards baseline. Conclusion: In CTP-2 deficiency, rhabdomyolysis may occur despite fibrate therapy. Patient education regarding the need to avoid dehydration, strenuous exercise and prolonged heat remain important components of management. doi:10.1016/j.hlc.2011.05.133 131 HDL Cholesterol is a Risk Factor for Diabetic Nephropathy But Not Retinopathy—Results From the ADVANCE Study J. Morton 1,∗ , Q. Li 2 , D. Celermajer 3 , J. Chalmers 2 , S. Zoungas 2 , A. Patel 2 , M. Ng 3 1 Heart
Research Institute, Australia George Institute, Australia 3 University of Sydney, Australia 2 The
Introduction: Although low HDL-C is a well known risk factor of atherosclerosis, data on HDL-C and risk of
Abstracts CSANZ Abstracts 2011
Heart, Lung and Circulation 2011;20S:S1–S155
ABSTRACTS
128 Australian Experience with LDL-apheresis for the Treatment of Severe Autosomal Dominant Hypercholesterolaemia (ADH)
130 Fenofibrate Therapy in Carnitine Palmitoyl Transferase2 Deficiency Improves Beta-oxidation of Fatty Acids But Does Not Prevent Rhabdomyolysis
M. Page 1,2,∗ , J. Burnett 1,2,3 , F. van Bockxmeer 3,4 , L. Southwell 1 , J. Gerace 5 , P. Cannell 5 , G. Watts 1,2
M. Yudi ∗ , I. Hamilton-Craig, A. Wright
1 Lipid
Disorders Clinic, Royal Perth Hospital, Perth, Australia 2 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia 3 Core Clinical Pathology and Biochemistry, Royal Perth Hospital, Perth, Australia 4 School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia 5 Haematology, Royal Perth Hospital, Perth, Australia Introduction: Low density lipoprotein (LDL)-apheresis offers radical therapy for severe or refractory dyslipidaemias. We have employed this treatment at Royal Perth Hospital since 2003 and herewith present our experience with the first cases of ADH. Methods: Retrospective review of hospital records and patient interviews: data extracted related to demographic, clinical and genetic status, laboratory and imaging findings, and LDL-apheresis procedures. Results: Three patients (Patient 1, female, aged 40 years at commencement; Patient 2, female, 34 years; Patient 3, female, 14 years) had homozygous ADH (compound heterozygous for mutations in the LDLR gene). Patient 4 had drug-intolerant, heterozygous familial defective apoB (due to a mutation in the APOB gene). LDL-apheresis was performed by cascade filtration, once every one to four weeks. 333 procedures were performed since 2003. Pretreatment LDL-cholesterol was 10.5 ± 4.6 mmol/L (range 7.1–16.9). The homozygous patients continued on maximal cholesterol-lowering drug therapy. Mean acute lowering of LDL-cholesterol with each procedure was 71.5 ± 11.9% (P = 0.002); long-term time-averaged lowering was 40.3 ± 22.7% (P = 0.003). There were also reductions in triglyceride, apoB and Lp(a). Serial ultrasonography of carotid arteries and Achilles tendons, and coronary angiography were consistent with stabilisation/regression of lesions. All patients remained clinically stable. Problems encountered included iron deficiency anaemia and minor reactions to a particular batch of filtration columns. The mean annual cost per patient was $30,688 (2010 prices). Conclusion: LDL-apheresis by cascade filtration is a safe, effective and well-tolerated treatment for severe hypercholesterolaemia and should be incorporated in clinical services for patients with ADH. doi:10.1016/j.hlc.2011.05.131 129 This abstract has been withdrawn.
Gold Coast Hospital, Australia Background: Carnitine palmitoyl transferase-2 (CTP2) deficiency is an autosomal recessive trait manifest in the adult by recurrent episodes of rhabdomyolysis, often precipitated by dehydration, heat exposure or vigorous exercise. CTP-2 deficiency results in defective transport of long-chain fatty acids across the mitochondrial membranes into the cytosol for beta-oxidation, resulting in defective ATP generation for normal muscular contraction and structural integrity. Fibrate therapy has been used to improve clinical and biochemical sequelae of CTP-2 deficiency. Case: A man with CTP-2 deficiency, diagnosed at age 19 years when rhabdomyolysis was precipitated by vigorous exercise, presented at age 59 years for management of hypercholesterolaemia. He had a five-year history of hypertension, controlled with lisinopril therapy, and a malignant melanoma was removed 10 years previously. He was intolerant of statin therapy because of myalgia. Fenofibrate 145 mg/day was commenced and plasma fatty acid profiles determined prior to and after six months of therapy. Plasma palmitoyl- and oleoylcarnitine levels improved, consistent with improved fatty acid beta-oxidation and CTP-2 activity. Myalgia and muscle cramping also improved. Three months later, while trekking in Fiji in temperatures >38 ◦ C he developed severe myalgia, weakness, fatigue and fever and presented to hospital in acute renal failure [creatinine 167 mol/L (RR < 108), CK 44,100 U/L (RR < 171)]. With fluid resuscitation he recovered without dialysis. Fenofibrate therapy was discontinued, with return of lipid profile towards baseline. Conclusion: In CTP-2 deficiency, rhabdomyolysis may occur despite fibrate therapy. Patient education regarding the need to avoid dehydration, strenuous exercise and prolonged heat remain important components of management. doi:10.1016/j.hlc.2011.05.133 131 HDL Cholesterol is a Risk Factor for Diabetic Nephropathy But Not Retinopathy—Results From the ADVANCE Study J. Morton 1,∗ , Q. Li 2 , D. Celermajer 3 , J. Chalmers 2 , S. Zoungas 2 , A. Patel 2 , M. Ng 3 1 Heart
Research Institute, Australia George Institute, Australia 3 University of Sydney, Australia 2 The
Introduction: Although low HDL-C is a well known risk factor of atherosclerosis, data on HDL-C and risk of