Vol. 84, No. 4 Printed in U.S.A.
CLINICAL CASE SEMINAR Prevention of Recurrent Pancreatitis in Familial Lipoprotein Lipase Deficiency with High-Dose Antioxidant Therapy
A. P. HEANEY, N. SHARER, B. RAMEH, J. M. BRAGANZA, P. N. DURRINGTON
University of Manchester,Departments of Medicine and Gastroenterology, Manchester Royal Infirmary, Manchester M13 9WL, United Kingdom
ABSTRACT We describe a dramatic response to antioxidant therapy in three patients with familial lipoprotein lipase deficiency complicated by frequent severe episodes of pancreatitis who had failed to respond to other dietary and pharmacological measures. Antoxidant therapy may be an importantadvance in the management of this type of patient. (J Clin Endocrinol Metab 84: 1203–1205, 1999)
Lipoprotein lipase removes triglycerides from the circulating triglyceride-rich lipoproteins (chylomicrons and verylow-density lipoproteins) and is located on the capillary endothelium of tissues such as adipose tissue and skeletal and cardiac muscle. Familial lipoprotein lipase deficiency (FLLD)(1, 2) is an autosomal recessive disorder caused by mutation of the gene for lipoprotein lipase (3). Frequently, the disorder is associated with grossly elevated serum triglyceride levels, sometimes as high as 100 mmol/L. It is refractory to lipidlowering drug therapy; and often, the only long-term means of treatment is the adoption of a diet that is low in all types of fat. Unfortunately, evenwith extremely restrictive diets (intended to contain as little as 10 g of fat each day), serum triglyceride levels are rarely maintained at values less than 20 mmol/L (2). Many patients with the disorder are prone to attacks of pancreatitis, and these are the source of considerable morbidity and premature mortality. We describe a novel approach to the prevention of pancreatitis using highdoseantioxidant therapy, which was highly effective in three patients with FLLD in whom attacks of pancreatitis were particularly frequent before the introduction of the new treatment.
In none of the three patients with FLLD, in this report, was lipoprotein lipase activity detectable in postheparin plasma, despite the demonstration of apolipoprotein CII (the circulating activator oflipoprotein lipase) in all three. The patients all had FLLD, complicated by pancreatic disease, and are a consecutive series treated with oral antioxidant therapy
Received July 24, 1998. Revision received November 26, 1998. Accepted November 30, 1998. Address all correspondence and requests for reprints to: P. N. Durrington, Department of Medicine, Manchester Royal Infirmary, Oxford Road, ManchesterM13 9WL, United Kingdom.
(AOT), initially as selenium- -carotene-C-E, two tablets three times daily (Wassen, Mole Park, UK), which provided -tocopherol (270 IU/day), -carotene (9000 IU/day), vitamin C (540 mg/day), and organic selenium (600 g/day), and a separate tablet of methionine (0.5 g qds; Evans, Chessington, UK) (4, 5). More recently Antox (Pharmanord, Morpeth, UK) has replaced thiscombination of supplements in similar doses (6). These maintain blood glutathione, plasma vitamin C and serum selenium levels towards the upper end of the reference range (4 – 6) and are pharmacological with respect to vitamin E and -carotene (Table 1). In none of the patients was there any discernible diminution in serum lipid levels after treatment (Table 2). None of the patients had diabetesmellitus, as defined by the World Health Organization, and none had an excessive alcohol intake. Patient TS had been always ill as a child. Lipoprotein lipase deficiency was diagnosed when she was 6 yr old. At the age of 18, after diagnostic laparotomy for severe abdominal pain, pancreatitis was diagnosed, and she required intensive care support, followed by surgical drainage of a pseudocyst. She...