Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new case of C-II anapolipoproteinemia (complete apolipoprotein C-II deficiency) as the cause of severe hypertriglyceridemia with chylomicronemia (type I lipoprotein phenotype) is described. The patient was a five-year-old boy living in Connecticut. He had splenomegaly, episodic abdominal pain, and bloody stools. Absence of apolipoprotein C-II (and its isoforms C-II1 and C-II2) was documented by a sensitive and specific radioimmunoassay, analytical isoelectric focusing, and in vitro lipolytic assay. Decreased levels of high- and low-density lipoprotein cholesterol and apolipoproteins A-I and A-II and increased levels of plasma triglycerides and apolipoprotein E were found. Post-heparin extra-hepatic lipoprotein lipase activity was within normal range. Incorporation of exogenous purified human apolipoprotein C-II to an incubation mixture of purified lipoprotein lipase and the patient's triglyceride-rich lipoproteins resulted in a dramatic increase in the catabolic rate of the defective triglyceride-rich lipoproteins. The absence of the isoforms of apolipoprotein C-II in this patient indicates that a common gene exists for the C-II isoproteins, which appear to be necessary for normal triglyceride transport in humans. A literature review of 23 reported cases indicates that xanthomas and hepatosplenomegaly are less common in C-II anapolipoproteinemia than in lipoprotein lipase deficiency, the other major etiologic cause of genetic chylomicronemia.
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PMID:C-II anapolipoproteinemia and severe hypertriglyceridemia. Report of a rare case with absence of C-II apolipoprotein isoforms and review of the literature. 647 85

We report a 39-year-old Japanese man with HDL and apoA-I deficiency as well as data from members of his family. Corneal opacity and a stomatocyte were found but not tonsillar hypertrophy, xanthomas, or splenomegaly. His serum HDL cholesterol, apoA-I, apoA-II, and LDL cholesterol levels were t mg/dL, < 3 mg/dL, 6 mg/dL, and 175 mg/dL, respectively. Plasma triglyceride, phospholipid, apoB, apoC-III, and apoE levels were all within normal limits. Lecithin:cholesterol acyltransferase activity was half of normal, while lipoprotein lipase and hepatic triglyceride lipase activities were within normal limits. ApoA-I deficiency was confirmed by combined isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by an immunoblotting method. We surveyed the apoA-I gene of the patient and five of his family members by direct sequencing after amplification by polymerase chain reaction and found a codon 8 nonsense mutation (TGG --> TAG, Trp --> stop) in exon 3 of the apoA-I gene. The results of a pedigree analysis by DNA sequencing and restricted fragment length polymorphism (Sty I) were consistent with an autosomal codominant trait. Coronary angiography was performed to evaluate coronary atherosclerosis, but no significant luminal narrowing was detected. An intracoronary ultrasound study showed mild intimal hyperplasia in segment 6. In summary, this is a case of apoA-I deficiency without evidence of coronary heart disease.
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PMID:A new case of apoA-I deficiency showing codon 8 nonsense mutation of the apoA-I gene without evidence of coronary heart disease. 758 66

A slight to moderate hemolysis is often present in plasma from patients with primary lipoprotein lipase (LPL) deficiency. To determine the nature of this hemolysis, we measured erythrocyte hypo-osmotic fragility, plasma free hemoglobin, and phospholipid composition in 26 patients with primary LPL deficiency and 21 unrelated controls. In some patients, these investigations were completed by erythrocyte cytoskeletal protein determinations and abdominal echography. Osmotic fragility was similar between control subjects and patients. However, there was a significantly increased concentration of plasma free hemoglobin in primary LPL deficiency (0.282 +/- 0.331 v 0.048 +/- 0.038 g/L in controls, P < .005). In LPL-deficient patients, an increase of plasma lysophosphatidylcholine concentration (12.6% +/- 5.8% v 6.4% +/- 1.9% in controls, P < .0001) was also found. The protein composition of the erythrocyte membrane skeleton was abnormal in some LPL-deficient patients and splenomegaly was present in 12, but these abnormalities did not correlate with plasma free hemoglobin levels. Bilirubin and haptoglobin levels were also within physiologic ranges in these patients, suggesting that the observed hemolysis did not result from hypersplenism. It appears likely that the accumulation of lysophosphatidylcholine was due to an impairment in the reverse metabolic pathway converting lysophosphatidylcholine back to phosphatidylcholine. Collectively, these data, along with a positive correlation between plasma free hemoglobin and lysophosphatidylcholine levels (r = .58, P = .0001), suggest that the hemolysis observed in primary LPL deficiency is mediated to some extent by the abnormally elevated concentration of lysophosphatidylcholine.
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PMID:Hemolysis in primary lipoprotein lipase deficiency. 775 15

Type III hyperlipoproteinemia (type III HLP) rarely manifests in childhood. Long-term follow-up (37 years) of the first patient revealed hypothyroidism at diagnosis requiring thyroxine replacement, palmar xanthomas requiring surgical removal, splenomegaly requiring splenectomy, 18 episodes of pancreatitis and premature coronary artery disease. Investigation revealed an apolipoprotein E phenotype of E2/E2 and partial lipoprotein lipase deficiency. Investigation of the second patient revealed a combination of apoE2/E2 phenotype and heterozygous familial hypercholesterolaemia. The third patient had a complete deficiency of lipoprotein lipase activity, an abnormal thyroid stimulating hormone on diagnosis (with subsequent normalisation without treatment), and apoE2/E2 phenotype. Type III HLP is a serious disorder with lifelong consequences of premature vascular disease and recurrent pancreatitis. Early presentation of disease in our patients was associated with additional precipitating factors. Drug treatment of paediatric type III HLP is indicated if dietary modifications alone are insufficient in managing the dyslipidaemia.
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PMID:Case series of type III hyperlipoproteinemia in children. 2269 86

A case of chylomicronemia syndrome is reported in a 72-year-old male with distinctive features of chronic pancreatic damage, severe hypertriglyceridemia, polidistrectual atherosclerosis and premature cognitive impairment. Although the patient had a positive history for recurrent episodes of pancreatitis the characteristic lesions of the hyperchylomicronemia syndrome, such as eruptive xanthomas and lipemia retinalis, were not present and splenomegaly could not be documented due to a previous post-traumatic splenectomy. Based on clinical phenotype, an apolipoprotein C-II deficiency was excluded by a fresh plasma infusion test, in which clarification of the patient plasma was not obtained. The absence of changes in the lipoprotein electrophoretic plasma after heparin infusion can be secondary to a lipoprotein lipase deficiency, a rare genetic disorder with an incidence of one per million. In relation to the resistance to diet and drugs, plasma exchange therapy was performed. After 3 years of this treatment there was no significant progression of atherosclerosis.
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PMID:Cognitive impairment and polidistrectual atherosclerotic disease in chylomicronemia syndrome: a case report. 2387 65

Background Familial apo C-II deficiency is a rare hereditary disorder frequently caused by lipoprotein lipase (LPL) and APOC2 gene mutations. To date, less than 30 patients with familial apo C-II deficiency with 24 different mutations have been identified in the literature. Here, we describe two familial chylomicronemia syndrome cases in infants with two novel mutations of the APOC2 gene. Case presentation Case 1, a 46-day-old female, was admitted to our hospital for evaluation due to the lipemic appearance of the blood sample. A clinical examination revealed hepatomegaly and lipemia retinalis. Triglyceride level of 6295 mg/dL was decreased with a strict low-fat diet, medium-chain triglycerides (MCT) oil-rich formula and omega-3 fatty acid supplementation. Due to low adherence to the diet, TG elevation was detected and fresh frozen plasma (10 mL/kg/day) was administered for 2 days. A novel homozygous p.Q25X (c.73C>T) mutation in the APOC2 gene was detected. Case 2, a 10-month-old female patient, referred to our center for the differential diagnosis of hyperlipidemia as her blood sample could not be assessed due to its lipemic appearance. Laboratory examinations showed a TG level of 4520 mg/dL which was reduced with a low-fat diet, MCT oil-rich formula and omega-3 fatty acid supplementation. Hepatosteatosis and splenomegaly were determined using abdominal sonography. A novel homozygous IVS2+6T>G (c.55+6T>G) mutation in the APOC2 gene was identified. Conclusions We describe two novel homozygous mutations (p.Q25X [c.73C>T] and IVS2+6T>G [c.55+6T>G]) in the APOC2 gene in infants with hyperchylomicronemia. To the best of our knowledge, Case 1 is the youngest patient with familial apo C-II deficiency in the literature to date.
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PMID:Severe hyperchylomicronemia in two infants with novel APOC2 gene mutation. 3030 97

This is a case report of a 35-year-old secundigravida woman with recurrent episodes of hypertriglyceridaemia-induced acute pancreatitis during pregnancy, which is a rare but serious complication in pregnancy. The woman was normal weight, and she was not known with any metabolic disorders, but she had idiopathic splenomegaly, which might be explained by the high triglyceride levels. Later genetic analysis revealed a lipoprotein lipase gene mutation known to cause hypertriglyceridaemia. This shows, that it is important to consider genetic aetiology in normal weight pregnant women with hypertriglyceridaemia and pancreatitis.
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PMID:[Hypertriglyceridaemia-induced pancreatitis during pregnancy caused by a genetic defect]. 3032 91