RESUMEN
Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ï¼15 mg/dL and apoB ï¼15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.
Asunto(s)
Abetalipoproteinemia/diagnóstico , Abetalipoproteinemia/terapia , Abetalipoproteinemia/sangre , Abetalipoproteinemia/patología , Apolipoproteínas B/sangre , LDL-Colesterol/sangre , Costo de Enfermedad , Manejo de la Enfermedad , Humanos , PronósticoAsunto(s)
Cardiología/normas , Evaluación Preclínica de Medicamentos , Dislipidemias/tratamiento farmacológico , Dislipidemias/terapia , Anciano , Anticolesterolemiantes/farmacología , Niño , LDL-Colesterol/sangre , Ensayos Clínicos como Asunto , Femenino , Humanos , Japón , Masculino , Factores de Riesgo , Triglicéridos/sangreRESUMEN
AIM: Lomitapide is an oral inhibitor of the microsomal triglyceride transfer protein used to treat homozygous familial hypercholesterolemia (HoFH); patients require a low-fat diet to minimize gastrointestinal adverse effects and dietary supplements to prevent nutrient deficiencies. We investigated the diet and nutritional status during lomitapide treatment. METHODS: Japanese patients with HoFH, who were in a phase 3 trial of lomitapide, were instructed to start low-fat diets with supplements of vitamin E and essential fatty acids 6 weeks before starting lomitapide treatment. Dietary education was conducted by registered dietitians 16 times during the study period, which included a pre-treatment run-in phase (Weeks ï¼6-0), a lomitapide treatment efficacy phase (Weeks 0-26) and a safety phase (Weeks 26-56). Two-day dietary records were collected at each dietary counseling session. Anthropometric and biochemical parameters were measured at Weeks 0, 26 and 56. RESULTS: Eight patients completed the 56 weeks of lomitapide treatment. Their median energy intakes derived from lipids were 19.2% and 17.9% during the efficacy and safety phases, respectively. "Fats and oils" intakes, and "Fatty meat and poultry" intakes in two patients, were successfully reduced to achieve low-fat diets. Although intakes of energy, fatty acids and fat-soluble vitamins did not differ significantly among phases, body weight, serum fatty acid levels and vitamin E concentrations were decreased at Week 26 as compared with Week 0. CONCLUSION: HoFH patients can adhere to low-fat diets with ongoing dietary counseling. Instructions about intakes of energy, fatty acids and fat-soluble vitamins, as well as periodic evaluations of nutritional status, are necessary.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Bencimidazoles/uso terapéutico , Dieta con Restricción de Grasas , Suplementos Dietéticos , Hiperlipoproteinemia Tipo II/terapia , Adulto , Anciano , Ensayos Clínicos Fase III como Asunto , Terapia Combinada , Femenino , Estudios de Seguimiento , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , PronósticoRESUMEN
BACKGROUND: The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. METHODS: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. CONCLUSIONS: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients.
Asunto(s)
Prestación Integrada de Atención de Salud , Hiperlipoproteinemia Tipo II/terapia , Cooperación Internacional , Brechas de la Práctica Profesional , Sistema de Registros , Proyectos de Investigación , Acceso a la Información , Conducta Cooperativa , Minería de Datos , Prestación Integrada de Atención de Salud/organización & administración , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/mortalidad , Almacenamiento y Recuperación de la Información , Objetivos Organizacionales , Resultado del TratamientoRESUMEN
AIM: The high-density lipoprotein cholesterol(HDL-C) level is a major negative risk factor for atherosclerotic diseases dependent on various lifestyle parameters. Changes in the lifestyle of Japanese individuals over the past several decades is believed to have increased their total cholesterol levels and the incidence of cardiovascular disease in Japan. It is therefore important to assess the long-term trends in the HDL-C levels with respect to public health in the community. METHODS: In this study, accumulated data for the serum/plasma HDL-C levels published in cohort studies and obtained during health checkup programs in Japan were analyzed with respect to timedependent changes. RESULTS: The levels of HDL-C have continuously and significantly increased over the past 20 years by 12-15% according to the National Health and Nutrition Study, other cohort studies and commercially available data. On the other hand, the non-HDL-cholesterol levels demonstrated no changes or only a slight decrease during the same period. This finding is consistent with several sets of data obtained from health checkup programs. The commercially measured levels of serum apoA-I, an independent parameter of serum HDL, also showed a similar long-term increase, supporting the above findings. CONCLUSION: We concluded that the serum/plasma HDL concentrations in Japanese individuals, selectively, have increased continuously and significantly over the past 20 years or more. The reasons for this phenomenon and the consequent public health outcomes have yet to be investigated.