BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a treatable autosomal recessive inherited metabolic disorder.It results from a deficiency of sterol 27-hydroxylase(CYP27A1),which is a mitochondrial cytochrome P450 enz...BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a treatable autosomal recessive inherited metabolic disorder.It results from a deficiency of sterol 27-hydroxylase(CYP27A1),which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis.Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain,eyes,tendons,and vessels,resulting in juvenile cataracts,tendon xanthoma,chronic diarrhea,cognitive impairment,ataxia,spastic paraplegia,and peripheral neuropathy.CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports.CASE SUMMARY A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied.The patient is a 47-year-old male,who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts,cerebellar ataxia,pyramidal signs and chronic diarrhea.There was a significant increase in the concentration of free fatty acid compared to normal range.Doppler ultrasound of the urinary system showed multiple left kidney stones,a right kidney cyst,and a hypoechoic area in the bladder,which could move with body position.Sagittal and axial magnetic resonance imaging(MRI)of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon,abnormal thickening of the plantar fat,and a small amount of exudation around the fascia in front of the Achilles tendon.Cerebral MRI suggested white matter(WM)demyelination and slight cerebral atrophy.The diagnosis was confirmed by targeted sequencing,which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene(c.435G>T,c.1263+1G>A).Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid.Sediments in the bladder disappeared after therapy.CONCLUSION CYP27A1 genetic analysis should be the definitive method for CTX diagnosis.This case suggests that urinary system diseases may be neglected in CTX patients.The clinical,biological,radiological,and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.展开更多
The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that aff...The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.展开更多
Phytochemical reinvestigation on the whole plants of Ypsilandra thibetica obtained four new spirostanol glycosides,named ypsilandrosides U-X(1-4),and one new cholestanol glycoside,named ypsilandroside Y(5).Their struc...Phytochemical reinvestigation on the whole plants of Ypsilandra thibetica obtained four new spirostanol glycosides,named ypsilandrosides U-X(1-4),and one new cholestanol glycoside,named ypsilandroside Y(5).Their structures have been established by extensive spectroscopic data and chemical methods.Among them,compound 4 is a rare spirostanol glycoside which possesses a novel 5(6→7)abeo-steroidal aglycone,while compound 1 is a first spiro-stanol bisdesmoside attached to C-3 and C-12,respectively,isolated from the genus Ypsilandra.The induced platelet aggregation activity of the isolates was tested.展开更多
基金Supported by Zhejiang Province Medical Science and Technology Project,No.2020RC061 and No.2019ZD021Jinhua Bureau of Science and Technology Project,No.2020-3-004.
文摘BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a treatable autosomal recessive inherited metabolic disorder.It results from a deficiency of sterol 27-hydroxylase(CYP27A1),which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis.Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain,eyes,tendons,and vessels,resulting in juvenile cataracts,tendon xanthoma,chronic diarrhea,cognitive impairment,ataxia,spastic paraplegia,and peripheral neuropathy.CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports.CASE SUMMARY A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied.The patient is a 47-year-old male,who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts,cerebellar ataxia,pyramidal signs and chronic diarrhea.There was a significant increase in the concentration of free fatty acid compared to normal range.Doppler ultrasound of the urinary system showed multiple left kidney stones,a right kidney cyst,and a hypoechoic area in the bladder,which could move with body position.Sagittal and axial magnetic resonance imaging(MRI)of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon,abnormal thickening of the plantar fat,and a small amount of exudation around the fascia in front of the Achilles tendon.Cerebral MRI suggested white matter(WM)demyelination and slight cerebral atrophy.The diagnosis was confirmed by targeted sequencing,which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene(c.435G>T,c.1263+1G>A).Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid.Sediments in the bladder disappeared after therapy.CONCLUSION CYP27A1 genetic analysis should be the definitive method for CTX diagnosis.This case suggests that urinary system diseases may be neglected in CTX patients.The clinical,biological,radiological,and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.
文摘The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.
基金supported by the National Natural Science Foundation of China (U1802287 and 32000280)the Ten Thousand Talents Plan of Yunnan Province for Industrial Technology Leading Talentsthe State Key Laboratory of Phytochemistry and Plant Resources in West China (P2019-ZZ02).
文摘Phytochemical reinvestigation on the whole plants of Ypsilandra thibetica obtained four new spirostanol glycosides,named ypsilandrosides U-X(1-4),and one new cholestanol glycoside,named ypsilandroside Y(5).Their structures have been established by extensive spectroscopic data and chemical methods.Among them,compound 4 is a rare spirostanol glycoside which possesses a novel 5(6→7)abeo-steroidal aglycone,while compound 1 is a first spiro-stanol bisdesmoside attached to C-3 and C-12,respectively,isolated from the genus Ypsilandra.The induced platelet aggregation activity of the isolates was tested.
