Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0154251 (lipid disorder)
 795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sitosterolemia (OMIM 210250) is a rare, autosomal recessive lipid disorder initially described almost 30 years ago. The disease is characterized by elevated plasma levels of plant sterols due to increased intestinal absorption and reduced biliary secretion of neutral sterols. Patients with sitosterolemia are frequently hypercholesterolemic, and develop xanthomas and premature coronary heart disease (CHD). Hemolysis, arthralgias and arthritis are also frequently associated with the disorder. Recently, sitosterolemia has been revealed to be due to mutations in either of the two ATP-binding cassette (ABC) half-transporters. ABCG5 or ABCG8. These two genes are expressed almost exclusively in the liver and intestine, and are co-regulated by the nuclear hormone receptor, liver X receptor (LXR). Genetically modified mice, which express either high levels or no ABCG5 and ABCG8 have been developed. Analyses of these mice confirm that these two transporters play key roles in regulating the absorption of dietary and biliary sterols, and in mediating the excretion of neutral sterols from the liver to the bile. The elucidation of the gene defects responsible for sitosterolemia provides potential therapeutic targets for the treatment of hyperlipidemias in the general population.
 ...
PMID:Sitosterolemia: a gateway to new knowledge about cholesterol metabolism. 1464 32

Sitosterolemia is a rare, autosomal recessively inherited disorder of lipid metabolism caused by mutations in the "ATP-binding cassette, subfamily G" member 5 and 8 proteins (encoded by the ABCG5 and ABCG8 genes, respectively), which play critical roles in the intestinal and biliary excretion of plant sterols. We report the clinical features and treatment outcomes of an 18-month-old Japanese girl with sitosterolemia, who presented with multiple linear and intertriginous xanthomas around the joint areas. Serum lipid analyses revealed elevated levels of total cholesterol (T-Chol: 866 mg/dL), low density lipoprotein-cholesterol (LDL-C: 679 mg/dL), and plant sterols (sitosterol: 24.6 mg/dL, campesterol: 19.2 mg/dL, stigmasterol: 1.8 mg/dL). Compound heterozygous mutations (p.R419H and p.R389H) were identified in ABCG5. The patient was placed on a low cholesterol/low plant sterol diet and treated with colestimide (a bile acid sequestrant) and ezetimibe (an NPC1L1 inhibitor). Serum T-Chol and LDL-C levels decreased to normal within 2 mo, and plant sterol levels decreased by 30% within 4 mo. The xanthomas regressed gradually, and almost completely disappeared after 1.5 yr of treatment. No further reductions of plant sterol levels were observed. Long-term follow-up is important to verify appropriate therapeutic goals to prevent premature atherosclerosis and coronary artery disease.
 ...
PMID:A case of sitosterolemia due to compound heterozygous mutations in ABCG5: clinical features and treatment outcomes obtained with colestimide and ezetimibe. 2820 44

Sitosterolemia is a rare lipid metabolism disease with heterogeneous manifestations. Atherosclerosis can occur in children, and therefore, early detection, diagnosis, and treatment of this disease are important. We studied 18 pediatric patients with sitosterolemia who showed a significant increase in plasma lipid levels and analyzed their clinical, biochemical, and genetic characteristics. We recorded the initial serum lipid results and clinical manifestations of the patients. Lipid and plant sterol levels were measured after homozygous or compound heterozygous mutations of ABCG5 or ABCG8 were identified by genetic testing. Plasma plant sterol levels were analyzed by gas chromatography. Fourteen cases of sitosterolemia were examined by ultrasound and echocardiography. The initial total cholesterol and low-density lipoprotein levels of the children were significantly increased, but then markedly decreased after diet control or drug treatment, and even reached normal levels. Carotid atherosclerosis and aortic valve regurgitation were present in three of 14 patients. Serum lipid levels of children with sitosterolemia and xanthomas were notably higher than those without xanthomas. There were no significant differences in clinical manifestations between patients with different genotypes. In conclusion, sitosterolemia should be considered in children with hyperlipidemia who do not present with xanthomas, especially with a significant increase in total cholesterol and low-density lipoprotein levels. There does not appear to be a correlation between clinical phenotype and genotype.
 ...
PMID:Features of Sitosterolemia in Children. 3214 15