Research progress of phytosterolemia and its laboratory diagnosis / 中华检验医学杂志

Phytosterolemia is a rare, severe autosomal recessive sterol storage disorder caused by homozygous or compound heterozygous mutations in one of the ABCG5 and/or ABCG8 adenosine triphosphate binding cassette (ABC) genes. The most prominent features of phytosterolemia are the significantly increased serum content of plant sterols. Present review focused on the laboratory diagnosis of phytosterolemia, briefly described the metabolism of phytosterols, and introduced the latest research progress on phytosterolemia diagnosis, its relationship with ASCVD and laboratory diagnostic methods (including the detection of serum concentrations of phytosterols, ABCG5/G8 gene mutation). We hope this article could improve readers′ awareness and attention on this disease.

Clinical phenotype, laboratory examination, gene diagnosis and literature review for 3 children with phytosterolemia / 临床检验杂志

Objective@#To study the characteristics of clinical diagnosis and treatment for 3 children with phytosterolemia. @*Methods@#The different clinical manifestations of 3 children with phytosterolemia were retrospectively reviewed. The case 1 and case 2, who were 7 years and 2 months old twin sisters, hospitalized for frequent epistaxis and abdominal pain. The case 3, who was 5 years and 7 months old male, came to the hospital for cutaneous xanthoma. The phytosterol levels in serum of the children were analyzed by gas chromatography-mass spectrometry, and the second generation sequencing method was used to analyze the disease-causing gene. Sanger sequencing method was used to verify the ABCG5 gene mutation and parental source. @*Results@#(1) The case 1 and case 2 showed moderate anemia, raised reticulocytes, total bilirubin and indirect bilirubin as well as splenomegaly. The blood smear showed that there were more irregular red blood cells, such as oral red blood cells, increased large/giant platelets, and ristomycin-induced platelet aggregation test was decreased. The urine routine examination indicated that there was bleeding in the urinary system. The results of blood lipid test were almost normal. The case 3 showed mild anemia with normal shape of erythrocyte and normal size of spleen. The large/giant platelets increased. The results of platelet aggregation test, bilirubin and urine routine examination were in normal range, but the levels of total cholesterol and low-density lipoprotein cholesterol increased significantly. (2) The levels of serum phytosterol were significantly increased in all the 3 children. (3) Two heterozygous mutations were detectable in ABCG5 gene of case 1 and 2 which were complex heterozygous mutation, i.e., c.9041G＞A and c.751C＞T. The variations were from their father and mother respectively. In case 3, only one homozygous mutation was detectable in ABCG5 gene which originated from their parents. @*Conclusion@#When the child showed increased large/giant platelets, hemolytic anemia, erythrocytosis or xanthoma of skin and rised total cholesterol and low-density lipoprotein cholesterol at first visit, the possibility of phytosterolemia should be considered. The blood phytosterol content and gene detection should be carried out as early as possible in order to treat early and improve prognosis.

Diagnosis and management of sitosterolemia / 国际儿科学杂志

Sitosterolemia is a rare autosomal recessive disorder,which is caused by increased intestinal absorption and decreased biliary excretion of plant sterols resulting from heterozygous mutations in either ABCG5 or ABCG8 gene.Sitosterolemia is characterized by increased serum plant sterol levels,hypercholesterolemia,xanthomas,accelerated atherosclerosis,and some patients have hematologic manifestations such as stomatocytic hemolysis,macrothrombocytopenia,etc.Early diagnosis can be made by serum plant sterol detection by gas chromatography mass spectrometry or liquid chromatography mass spectrometry,or ABCG5 and ABCG8 gene sequencing.The mainstay of therapy includes dietary restriction of both cholesterol and plant sterols,and the sterol absorption inhibitor or bile acid sequestrants.This article reviewed recent publication of sitosterolemia at home and abroad.

Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management

Sitosterolemia is an autosomal recessive disorder characterized by increased plant sterol levels, xanthomas, and accelerated atherosclerosis. Although it was originally reported in patients with normolipemic xanthomas, severe hypercholesterolemia have been reported in patients with sitosterolemia, especially in children. Sitosterolemia is caused by increased intestinal absorption and decreased biliary excretion of sterols resulting from biallelic mutations in either ABCG5 or ABCG8, which encode the sterol efflux transporter ABCG5 and ABCG8. Patients with sitosterolemia show extreme phenotypic heterogeneity, ranging from almost asymptomatic individuals to those with severe hypercholesterolemia leading to accelerated atherosclerosis and premature cardiac death. Hematologic manifestations include hemolytic anemia with stomatocytosis, macrothrombocytopenia, splenomegaly, and abnormal bleeding. The mainstay of therapy includes dietary restriction of both cholesterol and plant sterols and the sterol absorption inhibitor, ezetimibe. Foods rich in plant sterols include vegetable oils, wheat germs, nuts, seeds, avocado, shortening, margarine and chocolate. Hypercholesterolemia in patients with sitosterolemia is dramatically responsive to low cholesterol diet and bile acid sequestrants. Plant sterol assay should be performed in patients with normocholesterolemic xanthomas, hypercholesterolemia with unexpectedly good response to dietary modifications or to cholesterol absorption inhibitors, or hypercholesterolemia with poor response to statins, or those with unexplained hemolytic anemia and macrothrombocytopenia. Because prognosis can be improved by proper management, it is important to find these patients out and diagnose correctly. This review article aimed to summarize recent publications on sitosterolemia, and to suggest clinical indications for plant sterol assay.