RESUMO
Sitosterolemia is an autosomal recessive and very rare disease. Its main characteristic is that there is a greater absorption and a decrease in the excretion of sterols, which leads to them being deposited in tissues. It is given by mutations in the ABCG5 or ABCG8 genes found on chromosome 2p21. In this clinical note, we describe the first two patients with familial sitosterolemia described in Colombia, brothers, one of them with xanthomas in extremities as the only symptom, and the other, completely asymptomatic. Genetic studies were performed as a diagnostic test in both patients, where a pathogenic homozygous variant could be identified in the ABCG8 gene in the first case (symptomatic), and a heterozygous variant in the ABCG8 gene in the second case (asymptomatic); the first patient has responded to treatment with ezetimibe. In conclusion, xanthomas should be studied in depth in pediatric age as they may be the only visible sign of such complex and hereditary diseases as familial sitosterolemia, which can be controlled and prevent cardiovascular complications of the disease.
Assuntos
Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Ezetimiba , Hipercolesterolemia , Enteropatias , Erros Inatos do Metabolismo Lipídico , Fitosteróis , Humanos , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/diagnóstico , Masculino , Colômbia , Fitosteróis/efeitos adversos , Fitosteróis/genética , Enteropatias/genética , Enteropatias/diagnóstico , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Hipercolesterolemia/genética , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/diagnóstico , Ezetimiba/uso terapêutico , Xantomatose/genética , Xantomatose/patologia , Xantomatose/diagnóstico , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/administração & dosagem , Mutação , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Homozigoto , Criança , Heterozigoto , Lipoproteínas/genéticaRESUMO
PURPOSE OF REVIEW: The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either ABCG5 or ABCG8, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease. RECENT FINDINGS: Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in ABCG5 and ABCG8 in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in ABCG5/ABCG8 can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia. Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.
Assuntos
Aterosclerose , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Enteropatias , Erros Inatos do Metabolismo Lipídico , Fitosteróis , Xantomatose , Humanos , Hipercolesterolemia/tratamento farmacológico , Fitosteróis/efeitos adversos , Fitosteróis/genética , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/terapia , Enteropatias/diagnóstico , Enteropatias/genética , Enteropatias/tratamento farmacológico , Hiperlipoproteinemia Tipo II/complicações , Colesterol , Xantomatose/etiologia , Aterosclerose/genética , Aterosclerose/complicaçõesRESUMO
BACKGROUND AND AIMS: Phytosterol (PS) consumption is associated with lower total and LDL-cholesterol (LDL-c) concentrations, but its impact on cardiovascular risk is unclear. This study assessed the effect of usual intake of PS on markers of subclinical atherosclerosis in the Longitudinal Study of Adult Health (ELSA-Brasil). METHODS AND RESULTS: This cross-sectional study included 2560 participants of ELSA-Brasil, aged 48 (43-54) years, with available food frequency questionnaires (FFQ), coronary artery calcium (CAC) scores, carotid intima media thickness (cIMT), and carotid-femoral pulse wave velocity (cf-PWV), at baseline. Several logistic and linear regression models were used, and significance level was set at a P < 0.05. Mean values (SD) for PS consumption were 256 (198) mg/day, CAC 22.78 (110.54) Agatston Units, cf-PWV 9.07 (1.60) m/s and cIMT 0.57 (0.12) mm. PS consumption in Q4 was associated with lower total- and LDL-c levels, and with higher percentiles of cf-PWV (P < 0.001). Proportion of subjects in Q4 of PS consumption was 1.5 times higher among individuals in cf-PWV Q4, than in Q1 (P = 0.002, for comparisons among quartiles). There was a trend (P = 0.003) for higher cf-PWV with higher PS intake. In crude logistic and linear regressions, PS intake was associated with cf-PWV. In the adjusted models, these associations disappeared. No associations were found between PS and cIMT or CAC. CONCLUSIONS: In this large and apparently healthy cross-sectional sample from ELSA-Brasil, usual PS consumption was associated with lower total- and LDL-cholesterol, but not with markers of subclinical atherosclerosis.
Assuntos
Doenças das Artérias Carótidas/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Dieta , Fitosteróis/administração & dosagem , Calcificação Vascular/epidemiologia , Adulto , Biomarcadores/sangue , Brasil/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/prevenção & controle , Espessura Intima-Media Carotídea , Velocidade da Onda de Pulso Carótido-Femoral , LDL-Colesterol/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/prevenção & controle , Estudos Transversais , Dieta/efeitos adversos , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fitosteróis/efeitos adversos , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/prevenção & controle , Rigidez VascularRESUMO
BACKGROUND: Protein supplement use is common in bodybuilders because protein supplements are thought to increase muscle mass by preventing protein catabolism during exercise routines. Information on the consequences of protein supplement use is scarce and contradictory. Therefore, the identification of a kidney damage marker, such as microalbuminuria, could be transcendent in preventing probable organ compromise in healthy persons. The aim of this study is to determine the presence of microalbuminuria in gym members and whether there is an associated risk with protein supplement use. METHODS: An analytic, descriptive, cross-sectional study was conducted. It included gym members whose clinical and nutritional histories were taken, identifying protein supplement use. Microalbuminuria was then determined through a random urine sample. Descriptive and inferential statistics were used for the data analysis. The objective was to determine the presence of microalbuminuria in gym members and whether there is an associated risk with protein supplement use. RESULTS: A total of 107 gym members, 71 men and 36 women, that met the inclusion criteria of the study were analyzed. Their mean age was 35±13 years, and the prevalence of microalbuminuria was 9.34%. There was active protein supplement use in 58% of the study participants, with a mean consumption duration of 16±22 months. No association with the presence of microalbuminuria was found (P=0.35). CONCLUSIONS: The prevalence of microalbuminuria in gym members was higher than that of the general healthy population and was not associated with protein supplement use.
Assuntos
Albuminúria/etiologia , Diosgenina/efeitos adversos , Fitosteróis/efeitos adversos , Proteínas/metabolismo , Adulto , Albuminúria/metabolismo , Estudos Transversais , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Proteínas/efeitos adversos , Adulto JovemRESUMO
Sitosterolemia is an autosomal recessive metabolic disease caused by mutations in ABCG5 or ABCG8 genes which encode for the (ATP)-binding cassette (ABC) transporters that are responsible for the trafficking of xenosterols. Liver involvement is not a recognized manifestation of this disease, and cirrhosis has been reported only once in the medical literature. We describe a fatal case of a 21-year old South Asian male who presented with decompensated cirrhosis, and biochemical abnormalities consistent with sitosterolemia. Genetic testing showed a homozygous pathogenic mutation in ABCG5, confirming the diagnosis. Sitosterolemia is a rare, but likely under-recognized condition, and a high degree of suspicion is imperative to make the diagnosis. We propose that sitosterolemia should be included in the differential diagnosis for patients with cryptogenic cirrhosis, especially as there are effective oral therapies to treat this condition. Newly diagnosed sitosterolemia patients should undergo a thorough hepatology evaluation and follow-up to evaluate for the presence, development, and progression of any hepatic involvement.
Assuntos
Hipercolesterolemia/complicações , Enteropatias/complicações , Erros Inatos do Metabolismo Lipídico/complicações , Cirrose Hepática/etiologia , Fitosteróis/efeitos adversos , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Anemia Hemolítica/etiologia , Anticolesterolemiantes/uso terapêutico , Biópsia , Angiografia Coronária , Doença da Artéria Coronariana/etiologia , Análise Mutacional de DNA , Dieta com Restrição de Gorduras , Ezetimiba/uso terapêutico , Evolução Fatal , Predisposição Genética para Doença , Hereditariedade , Homozigoto , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/genética , Hipercolesterolemia/terapia , Enteropatias/diagnóstico , Enteropatias/genética , Enteropatias/terapia , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/terapia , Lipoproteínas/genética , Cirrose Hepática/diagnóstico , Masculino , Microscopia Eletrônica , Mutação , Linhagem , Fenótipo , Fitosteróis/genética , Fatores de Risco , Resultado do Tratamento , Xantomatose/etiologia , Adulto JovemRESUMO
OBJECTIVES: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE). STUDY DESIGN: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE. RESULTS: EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE. CONCLUSION: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status. TRIAL REGISTRATION: ClinicalTrials.govNCT01584206.
Assuntos
Anticolesterolemiantes/uso terapêutico , Ezetimiba/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Enteropatias/sangue , Enteropatias/tratamento farmacológico , Erros Inatos do Metabolismo Lipídico/sangue , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Fitosteróis/efeitos adversos , Adolescente , Adulto , Colestanol/sangue , Colestenonas/sangue , Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fitosteróis/sangue , Sitosteroides/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto JovemRESUMO
Specialty oils differ in fatty acid, phytosterol and antioxidant content, impacting their benefits for cardiovascular health. The lipid (fatty acid, phytosterol) and antioxidant (total phenolics, radical scavenging capacity) profiles of grapeseed (GSO), corn (CO) and coconut (CNO) oils and their physiological (triacylglycerides, total and HDL-cholesterol and antioxidant capacity (FRAP) in serum and fatty acid and phytosterol hepatic deposition) and genomic (HL, LCAT, ApoA-1 and SR-BP1 mRNA hepatic levels) responses after their sub-chronic intake (10% diet for 28 days) was examined in healthy albino rats. Fatty acid, phytosterol and antioxidant profiles differed between oils (p ≤ 0.01). Serum and hepatic triacylglycerides and total cholesterol increased (p ≤ 0.01); serum HDL-Cholesterol decreased (p < 0.05); but serum FRAP did not differ (p > 0.05) in CNO-fed rats as compared to CO or GSO groups. Hepatic phytosterol deposition was higher (+2.2 mg/g; p ≤ 0.001) in CO- than GSO-fed rats, but their fatty acid deposition was similar. All but ApoA-1 mRNA level increased in GSO-fed rats as compared to other groups (p ≤ 0.01). Hepatic fatty acid handling, but not antioxidant response, nor hepatic phytosterol deposition, could be related to a more efficient reverse-cholesterol transport in GSO-fed rats as compared to CO or CNO.
Assuntos
Antioxidantes/uso terapêutico , Gorduras Insaturadas na Dieta/uso terapêutico , Regulação da Expressão Gênica , Hiperlipidemias/prevenção & controle , Metabolismo dos Lipídeos , Fígado/metabolismo , Óleos de Plantas/uso terapêutico , Animais , Antioxidantes/efeitos adversos , Antioxidantes/análise , Antioxidantes/química , Biomarcadores/sangue , Biomarcadores/metabolismo , HDL-Colesterol/agonistas , HDL-Colesterol/antagonistas & inibidores , HDL-Colesterol/sangue , Óleo de Coco , Óleo de Milho/efeitos adversos , Óleo de Milho/química , Óleo de Milho/uso terapêutico , Gorduras Insaturadas na Dieta/efeitos adversos , Ácidos Graxos/efeitos adversos , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Ácidos Graxos/uso terapêutico , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Masculino , Capacidade de Absorbância de Radicais de Oxigênio , Fenóis/efeitos adversos , Fenóis/análise , Fenóis/uso terapêutico , Fitosteróis/efeitos adversos , Fitosteróis/análise , Fitosteróis/metabolismo , Fitosteróis/uso terapêutico , Óleos de Plantas/efeitos adversos , Óleos de Plantas/química , Óleos de Plantas/metabolismo , Distribuição Aleatória , Ratos Wistar , Sementes/química , Organismos Livres de Patógenos Específicos , Vitis/químicaRESUMO
Sitosterolemia is a disease characterized by an intestinal hyperabsorption of plant sterols and cholesterol. Affected individuals have mutations in both alleles of either ABCG5 or ABCG8 genes, leading to a total loss of one of the proteins and subsequent functional deficiency. We here report a Mexican family with clinical and biochemical features of sitosterolemia carrying 2 new mutations of the ABCG5 gene. Concentrations of sitosterol, campesterol, and cholesterol were found to be higher for the index case (a 10-year-old girl) than for her also affected sibling (64.1 vs 19 mg/dL, 32 vs 12.1 mg/dL, and cholesterol 295 vs 235 mg/dL, respectively). Both individuals showed 2 new ABCG5 gene mutations identified by sequencing, which is concordant with their biochemical diagnosis of sitosterolemia. The first mutation was a c.144 -1G>A transition that disrupts the intron 1 splicing acceptor site. The second mutation is the deletion c.1523 delC, which occurred in exon 11, causing an amino acid change at codon 510 (p.His510Thr) and a stop codon at codon 511 (p.Leu511X). The father is heterozygote for the mutation c.144 -1G>A, whereas the mother is heterozygote for the mutation c.1523 delC. In conclusion, we here report the first case of a Mexican family with sitosterolemia carrying two new ABCG5 gene mutations.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Hipercolesterolemia/genética , Enteropatias/genética , Erros Inatos do Metabolismo Lipídico/genética , Lipoproteínas/genética , Mutação , Linhagem , Fitosteróis/efeitos adversos , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adolescente , Sequência de Bases , Criança , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fitosteróis/genética , Adulto JovemRESUMO
OBJECTIVE: Plant sterol (PS) supplementation has been widely used alone or combined with lipid-lowering therapies (LLTs) to reduce low-density lipoprotein (LDL) cholesterol. The effects of PS added to high-intensity LLT are less reported, especially regarding the effects on cholesterol synthesis and absorption. METHODS: A prospective, randomized, open-label study, with parallel arms and blinded end points was designed to evaluate the effects of addition of PS to LLT on LDL cholesterol, markers of cholesterol synthesis, and absorption. Eighty-six patients of both genders were submitted to a 4-wk run-in period with atorvastatin 10 mg (baseline). Following, subjects received atorvastatin 40 mg, ezetimibe 10 mg, or combination of both drugs for another 4-wk period (phase I). In phase II, capsules containing 2.0 g of PSs were added to previous assigned treatments for 4 wk. Lipids, apolipoproteins, plasma campesterol, ß-sitosterol, and desmosterol levels were assayed at all time points. Within and between-group analyses were performed. RESULTS: Compared with baseline, atorvastatin 40 mg reduced total and LDL cholesterol (3% and 22%, respectively, P < .05), increased ß-sitosterol, campesterol/cholesterol, and ß-sitosterol/cholesterol ratios (39%, 47%, and 32%, respectively, P < .05); ezetimibe 10 mg reduced campesterol and campesterol/cholesterol ratio (67% and 70%, respectively, P < .05), and the combined therapy decreased total and LDL cholesterol (22% and 38%, respectively, P < .05), campesterol, ß-sitosterol, and campesterol/cholesterol ratio (54%, 40%, and 27%, P < .05). Addition of PS further reduced total and LDL cholesterol by â¼ 7.7 and 6.5%, respectively, in the atorvastatin therapy group and 5.0 and 4.0% in the combined therapy group (P < .05, for all), with no further effects in absorption or synthesis markers. CONCLUSIONS: PS added to LLT can further improve lipid profile, without additional effects on intestinal sterol absorption or synthesis.