#238600
ICD+
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| HYPERLIPOPROTEINEMIA, TYPE I | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative titles; symbols | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| LIPOPROTEIN LIPASE DEFICIENCY LPL DEFICIENCY HYPERCHYLOMICRONEMIA, FAMILIAL HYPERLIPEMIA, IDIOPATHIC, BURGER-GRUTZ TYPE HYPERLIPEMIA, ESSENTIAL FAMILIAL LIPASE D DEFICIENCY LIPD DEFICIENCY HYPERLIPOPROTEINEMIA, TYPE IA CHYLOMICRONEMIA, FAMILIAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinical Synopsis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| A number sign (#) is used with this entry because type I hyperlipoproteinemia can be caused by mutation in the lipoprotein lipase gene (LPL; 609708). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Features | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holt et al. (1939) first reported the familial occurrence of this syndrome. Boggs et al. (1957) described 3 affected sibs from a first-cousin mating. Massive hyperchylomicronemia occurs when the patient is on a normal diet and disappears completely in a few days on fat-free feeding. On a normal diet alpha and beta lipoproteins are low. A defect in removal of chylomicrons (fat induction) and of other triglyceride-rich lipoproteins (carbohydrate induction) is present. Decreased plasma postheparin lipolytic activity (PHLA) is demonstrated. Low tissue activity of lipoprotein lipase was suspected. The full-blown disease, manifested by attacks of abdominal pain, hepatosplenomegaly, eruptive xanthomas, and lactescence of the plasma, is a recessive. Heterozygotes may show slight hyperlipemia and reduced PHLA. Precocious atherosclerosis does not seem to be a feature. Havel and Gordon (1960) first recognized deficiency of lipoprotein lipase (triacylglycerol acylhydrolase; EC 3.1.1.3) as the basic defect in type I hyperlipoproteinemia. The type I hyperlipoproteinemia phenotype can also result from deficiency of the activator of lipoprotein lipase, apolipoprotein C-II (Breckenridge et al., 1978)--see 207750. This condition was called fat-induced hypertriglyceridemia by Nevin and Slack (1968). Adipose tissue in heterozygotes shows intermediate levels of lipoprotein lipase. Berger (1987) reported a case of variant lipoprotein lipase deficiency in which muscle lipoprotein lipase was essentially normal although the enzyme in adipose tissue was markedly reduced. Schreibman et al. (1973) studied a family with 2 clinically typical sibs whose lipoprotein lipase showed abnormal substrate specificity and kinetics. Hoeg et al. (1983) reported an extraordinary patient in whom the diagnosis was first made at the age of 75. Absolute abstinence from alcohol and a self-imposed low-fat diet may have been responsible for the long survival. Since childhood, he had had recurrent abdominal pain, nausea and vomiting, diagnosed as 'gall bladder attacks,' until age 48 when he was first hospitalized. During the next 15 years he had 1 to 3 episodes of abdominal pain per year necessitating hospitalization. These episodes were diagnosed as acute pancreatitis and were sometimes associated with an evanescent papular rash. Jaundice that developed rapidly at age 64 was found to be due to bile duct stenosis, which was surgically relieved. He had, at age 73, ischemic heart disease and a femoral bruit. Eckel (1989) provided an extensive review of lipoprotein lipase. Auwerx et al. (1989) classified LPL deficiency at the protein level on the basis of the absence (class I) or presence of defective enzyme protein, and whether it binds (class II) or does not bind (class III) to heparin. Slight to moderate hemolysis is often present in plasma from patients with primary LPL deficiency. Cantin et al. (1995) found that, while osmotic fragility was similar to that in control subjects, plasma prehemoglobin was significantly increased. Furthermore, an increase in plasma lysophosphatidylcholine concentration was found. This was thought to be due to an impairment in the reverse metabolic pathway converting lysophosphatidylcholine back to phosphatidylcholine. The findings, along with a positive correlation between plasma prehemoglobin and lysophosphatidylcholine levels, suggested that the hemolysis in LPL deficiency is mediated to some extent by the abnormally elevated concentration of lysophosphatidylcholine. Feoli-Fonseca et al. (1998) reviewed the cases of 16 infants under 1 year of age who were found to have LPL deficiency; 7 presented with irritability, 2 with lower intestinal bleeding, 5 with pallor, anemia, or splenomegaly, and 2 with a family history or fortuitous discovery. All plasma samples were lactescent at presentation. Kawashiri et al. (2005) reported a 22-year-old Japanese male with this mutation who had had no major pancreatic malformations, vascular complications, or severe glucose intolerance despite a 32-year clinical history of pancreatitis recurring more than 20 times. Based on the long-term observations of this patient, Kawashiri et al. (2005) proposed that LPL deficiency is not invariably associated with high mortality and that even with repeated episodes of acute pancreatitis, pancreatic function may be slow to decline. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Management | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| In the patients reviewed by Feoli-Fonseca et al. (1998), chylomicronemia responded rapidly to dietary fat restriction, and it was possible to maintain satisfactory metabolic control for a prolonged period of time. Only 1 adolescent girl had an episode of pancreatitis associated with the use of oral contraceptives. No persistent adverse effects on growth were seen. The development of pancreatitis indicates that estrogen therapy should be avoided in LPL-deficient patients. Heaney et al. (1999) reported a dramatic response to antioxidant therapy (Antox, 1 tablet 4 times daily) in 3 patients with familial lipoprotein lipase deficiency complicated by frequent severe episodes of pancreatitis. Because these patients failed to respond to other dietary and pharmacologic measures, the authors concluded that antioxidant therapy may be an important advance in the management of this type of patient. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| For a full discussion of the molecular genetics of lipoprotein lipase deficiency (type I hyperlipoproteinemia), see the entry for the LPL gene (609708). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| See Also: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Berger et al. (1962); Brunzell et al. (1980); Emi et al. (1990); Franklin (1937); Fredrickson and Levy (1972); Henderson et al. (1991); Sternowsky et al. (1977); Wessler and Avioli (1969) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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