1/77. Surgical excision of the tendon xanthoma in familial hypercholesterolemia--a case report.Familial hypercholesterolemia is an autosomal dominant disorder characterized by increased low-density lipoprotein cholesterol, premature atherosclerosis and tendon xanthomas. Genetic studies reveal familial hypercholesterolemia to be a dysfunction of LDL receptor gene on cell surface. Recently various mutations in the LDL receptor gene have been reported. When dna method is not available, the occurrence of tendon xanthomas, an isolated elevation of plasma cholesterol, with a normal concentration of plasma triglycerides virtually establishes the diagnosis of familial hypercholesterolemia. In this report, a 42-year-old male had tendon xanthoma at extensor surface of metacarpophalangeal joint of his right hand, olecranon of the left elbow and both knees, and Achilles tendons. The tendon xanthoma was excised for cosmetic reasons, and the wound healing was slower than average in this case. We suggest that before suture removal, wound healing must be complete. It is important that the hand surgeon recognize that tendon xanthoma is a physical sign of a potentially life-threatening disorder to the patient as well as his family, and that this disorder may respond favorably to early examination and management.- - - - - - - - - - ranking = 1keywords = xanthoma (Clic here for more details about this article) |
2/77. Familial hypercholesterolemia. Acceptor splice site (G-->C) mutation in intron 7 of the LDL-R gene: alternate rna editing causes exon 8 skipping or a premature stop codon in exon 8. LDL-R(honduras-1) [LDL-R1061(-1) G-->C].Familial hypercholesterolemia (FH) is an autosomal dominant lipoprotein disorder caused by defects in the low density lipoprotein (LDL) receptor (R) gene. We report a novel mutation of the LDL-R gene in a 38-year-old man with homozygous FH from the province of Trujilo in Northern honduras. The patient presented with tendinous xanthomas over the extensor tendons as well as xanthelasmas at sites of surgical scars. He was diagnosed with severe coronary artery disease requiring revascularization at age 29. After an unsuccessful course of treatment with simvastatin, the patient has been treated with plasma apheresis and macromolecular plasma filtration bi-monthly. Haplotyping of the LDL-R gene revealed homozygosity for the rare 'J' allele and a loss of the EcoRV restriction cleavage site in exon 8. Single stranded conformational polymorphism of exons 3, 6, 7, 9, 10 and 8 reveals an abnormal migration pattern in exon 8. Direct sequencing of the promoter region, exons 1, 4, 8 and 13 revealed two RFLP's and a novel mutation in intron 7. This mutation consists of G-->C transposition at the acceptor splice site of exon 8 at the last nucleotide of intron 7 [LDL-R1061(-1)G-->C]. Reverse transcriptase (RT) PCR amplification of RNA from monocytes obtained from the patient reveals a decrease in LDL-R mRNA (52% of control) and skipping of exon 8 (approximately 38%, as assessed by densitometric scanning of the amplified fragments) to form a new RNA transcript that includes exons 7 and 9 without frameshift. Alternative rna editing leads to a new cryptic acceptor splice site 17 bp downstream in exon 8 producing a frameshift mutation and a predicted premature stop codon 1138 bp from the transcriptional start site (approxiamtely 62%). Western blotting analysis using a monoclonal antibody (C7) directed at the amino terminus of the LDL-R protein reveals a marked reduction in LDL-R protein expressed in monocytes obtained from the patient. We conclude that LDL-R1061(-1)G-->C is a novel mutation of the LDL-R gene that results in marked decrease in LDL-R mRNA levels and protein expression by two alternate rna editing mechanisms, that cause skipping of exon 8 or the use of a novel cryptic acceptor splice site in exon 8 with a frameshift and premature stop codon. The patient continues to do well on selective plasma filtration but developed bilateral severe carotid artery disease requiring surgical intervention.- - - - - - - - - - ranking = 0.11111111111111keywords = xanthoma (Clic here for more details about this article) |
3/77. Extensive intracranial xanthoma associated with type II hyperlipidemia.Xanthomas are associated with a spectrum of medical conditions, most commonly disorders of lipid storage and lipid metabolism. They occur primarily in the subcutaneous tissues, especially along the achilles tendon and the extensor tendons of the hands. Intracranial xanthomas are extremely rare. We present a case of an extensive xanthoma of the temporal bone in a patient with hyperlipidemia.- - - - - - - - - - ranking = 0.66666666666667keywords = xanthoma (Clic here for more details about this article) |
4/77. Long-term (14 years) effect of LDL apheresis on obstructive changes in aortocoronary saphenous-vein bypass grafts in a case of heterozygous familial hypercholesterolemia with the LDL receptor proline664 to leucine mutation.A 61-year-old Japanese woman with heterozygous familial hypercholesterolemia (FH), type 2 diabetes mellitus and coronary artery disease underwent coronary artery bypass grafting (CABG) utilizing a saphenous vein graft at the age of 46, in June 1984, 6 months before low density lipoprotein (LDL) apheresis was started. She had received LDL apheresis every two weeks, along with combined drug treatment since the age of 47 (December 1984). She had bilateral xanthelasma and achilles tendon xanthomas. Her fasting baseline serum total cholesterol and triglyceride level were 464 mg/dl and 57 mg/dl, respectively at the age of 47 when she visited our hospital for the first time. Analysis of the genomic dna from the patient revealed heterozygous amino acid substitution of Leu for Pro664 in the LDL receptor gene. She was diagnosed as type 2 diabetes mellitus at the age of 53. Combined treatment in the steady state yielded a pretreatment LDL cholesterol level of 230 /-14 mg/dl and a posttreatment level of 57 /-7.6. All grafts were widely patent after as long as 14 years since CABG, suggesting that LDL apheresis combined with drug therapy is highly effective in preventing the occlusion of bypass grafts in a patient with heterozygous FH and type 2 diabetes mellitus.- - - - - - - - - - ranking = 0.11111111111111keywords = xanthoma (Clic here for more details about this article) |
5/77. Familial homozygous hypercholesterolemia: effective long-term treatment with cascade double filtration plasmapheresis.BACKGROUND: Homozygous familial hypercholesterolemia (FH) is a rare disease with an incidence of 1 in 1 million births. It is characterized by blood cholesterol levels over 600 mg/dl and the development of extensive cutaneous xanthomata before the age of 5. Severe premature coronary artery disease results in fatal myocardial infarctions within the first two decades of life. The absence of LDL receptors makes homozygous FH resistant to treatment with most HMG-CoA reductase inhibitors, and alternative methods of removing cholesterol have been employed. methods: We used the ASAHI plasauto-IQ double filtration cascade plasmapheresis to treat 2 young brothers aged 14 and 11 years and 6 months for 5 years and 1 month and 3 years and 10 months, respectively. The elder brother has received 136 double filtration treatments at 2-week intervals and the younger brother 100 such treatments without complications. RESULTS: During the period of treatment the average pretreatment total serum cholesterol level for patient 1 was 442 mg/dl. The average posttreatment value was 163 mg/dl. The average fall in total serum cholesterol with each treatment was 63.2%. The mean total serum cholesterol for all the periods of treatment was calculated at 303 mg/dl. For the 2nd patient, the average pretreatment value of total serum cholesterol was 435 mg/dl. The posttreatment value was 124 mg/dl and the average fall 71.5%. The calculated mean total serum cholesterol for all periods of treatment was 280 mg/dl. CONCLUSIONS: Double filtration cascade plasmapheresis at 2-week intervals provides an effective and safe long-term treatment for patients with homozygous FH. The achieved reduction in serum cholesterol allows complete resolution of cutaneous xanthomata, arrests previous atherosclerosis, and prolongs normal life.- - - - - - - - - - ranking = 0.22222222222222keywords = xanthoma (Clic here for more details about this article) |
6/77. A Chinese homozygote of familial hypercholesterolemia: identification of a novel C263R mutation in the LDL receptor gene.Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR) gene; it is characterized by a high concentration of LDL, which frequently gives rise to tendon xanthomas and premature coronary artery disease (CAD). Individuals with heterozygous FH in china often exhibit a milder phenotype than those in other countries. The diagnosis of heterozygous FH relies on the clinical phenotype and this does not always permit unequivocal diagnosis of the disease. In the course of investigation of FH in a Chinese population sample, we found a family whose proband showed a markedly raised concentration of LDL cholesterol in plasma, and the presence of skin and tendon xanthomata. We used single-strand conformation polymorphism (SSCP) analysis to screen all the 18 exons and the exon-intron boundaries of the LDLR gene. One novel homozygous mutation, replacing T by C at nucleotide 850 in exon 6 was identified. This change substituted cysteine for arginine at codon 263 (C263R) of the LDLR. By means of mutant allele-specific amplification, we unequivocally diagnosed six heterozygotes with this novel mutation in the proband's family. forms of heterozygous FH are characterized by high serum LDL cholesterol levels, which are usually associated with premature coronary heart disease (CHD) and tendon xanthomas in early middle age, while homozygous FH individuals frequently suffer fatal CHD by their third decade (Goldstein et al. 1995). To date, more than 200 different mutations of the LDLR gene have been characterized worldwide (Hobbs et al. 1990; Hobbs et al. 1992; Varret et al. 1997). Chinese individuals with heterozygous FH are often recognized by virtue of their being parents of offspring with mutations in both alleles of the LDLR gene (Mak et al. 1998). Unlike their heterozygous parents, the Chinese homozygous FH patients are as severely affected, as are those elsewhere (Sun et al. 1994). In this article, we present an investigation of a Chinese family whose proband, with severe hypercholesterolemia, carried a novel mutation of the LDLR gene in a homozygous form, while the other six patients in the family, who carried this mutation in a heterozygous form, have a milder phenotype of FH. The main objective of our analysis was to delineate the full spectrum of mutations that underline FH in the Chinese population; our work represents a first step towards the implementation of nationwide dna testing for this disease.- - - - - - - - - - ranking = 0.33333333333333keywords = xanthoma (Clic here for more details about this article) |
7/77. Visual disturbance due to carotid artery thrombosis in a patient with familial hypercholesterolemia; response to surgical thrombotectomy.A 48 years-old Japanese man suffered from marked xanthomas on ankles, knees, hand fingers, and foot joints due to insufficient control of serum hypercholesterolemia despite low density lipoprotein (LDL-C) absorptive therapy followed by treatment with potent anti-hypercholesterolemic agents. He had undergone surgical resection of xanthoma on the knee, foot and hand finger joints. Treatment with simvastatin returned the serum total cholesterol levels to nearly normal levels, followed by marked fluctuations. He subsequently experienced transient right-visual disturbance, and roentogenographic examination was performed. The patient was diagnosed as right-common carotid artery thrombosis. After the thrombotectomy of the right-common carotid artery, his visual power was markedly improved.- - - - - - - - - - ranking = 0.22222222222222keywords = xanthoma (Clic here for more details about this article) |
8/77. Japanese sisters associated with pseudohomozygous familial hypercholesterolemia and sitosterolemia.Pseudohomozygous familial hypercholesterolemia is a rare condition of unknown etiology. Sitosterolemia is a rare autosomal recessively inherited disorder that is characterized by premature coronary artery disease, cutaneous xanthomas, and increased plasma plant sterols and 5alpha-stanols. Only a few cases of both sitosterolemia and pseudohomozygous familial hypercholesterolemia have been reported. In this study, we report two sisters with both conditions. With a low-cholesterol diet (< 250 mg/day), serum cholesterol concentration decreased rapidly to an almost normal level and cutaneous xanthomas gradually regressed and finally disappeared; however, plant sterol levels did not change during the period. Plant sterols should be measured in patients considered to have pseudohomozygous familial hypercholesterolemia. The two conditions in this family may have been the results of a single gene mutation. The findings also indicate that low cholesterol diet therapy is effective for the treatment of hypercholesterolemia but not of sitosterolemia in this family.- - - - - - - - - - ranking = 0.22222222222222keywords = xanthoma (Clic here for more details about this article) |
9/77. plasma exchange and heart-liver transplantation in a patient with homozygous familial hypercholesterolemia.A female patient born in 1950 underwent plasma exchange and concomitant drug therapy for 20 yr due to homozygous familial hypercholesterolemia. plasma exchange reduced total cholesterol levels from 25-30 mmol/L (967-1160 mg/dL) before treatment to 9.5 mmol/L (363 mg/dL) with regression of xanthomas and no side effects of long-term treatment. Due to end-stage calcific left ventricular outflow tract obstruction not amenable to standard valve reconstructive surgery, a combined heart-liver transplantation was successfully performed in 1996. She is without symptoms and living a normal life 4 yr after transplantation. Total cholesterol value is normal (4.7 mmol/L [182 mg/dL]) using a moderate dose of statins. Selective coronary angiography is without signs of graft vascular disease and the liver function is normal.- - - - - - - - - - ranking = 0.11111111111111keywords = xanthoma (Clic here for more details about this article) |
10/77. Cellular pathology of homozygous familial hypercholesterolemia.tissues were studied from four subjects with homozygous familial hypercholesterolemia (FH). The specimens consisted of tissues obtained from a 20-week-old fetus at autopsy, samples from a 9-year-old girl during open-heart surgery, and biopsies of cutaneous xanthomas from a 13-year-old girl and a 21-year-old man. The FH fetus, but not the 3 control fetuses, exhibited multifocal lipid deposition particularly involving the stromal cells of the thymus, spleen, and skin and both the stromal and parenchymal cells of the kidney. Only one minute focus of intimal lipid accumulation was found in the aorta and coronary arteries of the FH fetus. A segment of the ascending aorta from the 9-year-old girl showed: 1) foam-cell transformation of many medial smooth-muscle cells, 2) abnormal vascularization of the inner media and intima, and 3) intimal involvement by a typical artherosclerotic plaque with lipid deposits in thin, elongated cells that showed some myocytic features and in foam cells that lacked such features. The mitral and aortic valves of this patient also contained numerous foam cells and showed mild to moderate fibrous thickening. A segment of the saphenous vein, however, contained no lipid deposits. The three xanthomas from two FH homozygotes exhibited marked lipid accumulation in histiocytic foam cells but no lipid deposits in the endothelium of blood vessels in the lesions. The findings in this study, in conjunction with those reported in studies of other FH homozygotes, indicate that homozygous FH is characterized by accelerated atherosclerosis and prominent lipid accumulation in macrophages and other stromal cells of the aortic and mitral valves, skin, tendon, and, varibly, in other extravascular sites. Since most of the intracellular lipid was in the form of non-membrane-bound neutral lipid droplets, it appears that the cytoplasm is the major site of lipid storage in this disease.- - - - - - - - - - ranking = 0.22222222222222keywords = xanthoma (Clic here for more details about this article) |
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