RESUMEN
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.
Asunto(s)
Aterosclerosis , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Enfermedades Intestinales , Errores Innatos del Metabolismo Lipídico , Fitosteroles , Xantomatosis , Humanos , Hipercolesterolemia/tratamiento farmacológico , Fitosteroles/efectos adversos , Fitosteroles/genética , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/terapia , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/genética , Enfermedades Intestinales/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/complicaciones , Colesterol , Xantomatosis/etiología , Aterosclerosis/genética , Aterosclerosis/complicacionesRESUMEN
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.
Asunto(s)
Hipercolesterolemia/complicaciones , Enfermedades Intestinales/complicaciones , Errores Innatos del Metabolismo Lipídico/complicaciones , Cirrosis Hepática/etiología , Fitosteroles/efectos adversos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/genética , Anemia Hemolítica/etiología , Anticolesterolemiantes/uso terapéutico , Biopsia , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/etiología , Análisis Mutacional de ADN , Dieta con Restricción de Grasas , Ezetimiba/uso terapéutico , Resultado Fatal , Predisposición Genética a la Enfermedad , Herencia , Homocigoto , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/genética , Hipercolesterolemia/terapia , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/genética , Enfermedades Intestinales/terapia , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/terapia , Lipoproteínas/genética , Cirrosis Hepática/diagnóstico , Masculino , Microscopía Electrónica , Mutación , Linaje , Fenotipo , Fitosteroles/genética , Factores de Riesgo , Resultado del Tratamiento , Xantomatosis/etiología , Adulto JovenRESUMEN
Mutation in ABHD5 causes Dorfman-Chanarin syndrome (DCS), a multisystem triglyceride storage disorder. Ultrastructural study of leukocytes confirmed DCS in a child homozygous for a novel ABHD5 mutation, with ichthyosis, developmental delay, and steatohepatitis with cirrhosis, manifest only as elevated aminotranferase levels. We recommend early assessment for liver disease in DCS.
Asunto(s)
Hígado Graso/etiología , Hepatitis/etiología , Errores Innatos del Metabolismo Lipídico/complicaciones , Cirrosis Hepática/etiología , Triglicéridos/metabolismo , 1-Acilglicerol-3-Fosfato O-Aciltransferasa , Niño , Esterasas/genética , Hígado Graso/diagnóstico , Hígado Graso/terapia , Femenino , Hepatitis/diagnóstico , Hepatitis/terapia , Humanos , Lipasa/genética , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/terapia , Cirrosis Hepática/patología , Cirrosis Hepática/terapia , SíndromeRESUMEN
Continuous venovenous hemofiltration was used to treat two neonates, one with maple syrup urine disease and the other with an inborn error of long-chain fatty acid oxidation. The latter infant had hypoglycemia, hyperammonemia and lactic acidosis. In both cases, acceptable biochemical control was achieved within 8 hours. This therapy offers the potential to overcome acute crises rapidly in a wide range of inborn errors of intermediary metabolism.