Familial Hypercholesterolemia / Монголын Анагаах Ухаан

@#Familial hypercholesterolemia (FH) (OMIM#143890) is the most common metabolic autosomal disorder. The prevalence of the homozygous FH has been reported as 1 in a million in the general population, compared to much more mild form heterozygous FH with prevalence of 1 in 200-500. Mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (ApoB), proprotein convertase subtilin/kexin9 (PCSK9), and low-density lipoprotein receptor adapter protein 1 (LDLRAP1) genes have been linked to FH. These mutations result in a disorder in low-density lipoprotein cholesterol (LDL-C) catabolism, and significantly increasing the levels of LDL-C, total cholesterol in serum, leading to specific clinical signs such as tendon xanthoma, corneal arcus, cardiovascular diseases, and early death from coronary heart disease if left unattended. Therefore, there is an ardent need for early diagnosis followed by aggressive therapeutic intervention and lifestyle modification. Currently, FH can be diagnosed either clinically or genetically. There have three main clinical diagnostic criteria for FH: the US MedPed Program, the Simon Broom Register Group in the UK, and the Netherland’s criteria. The occurrence of so many different LDLR mutations and their widespread distribution throughout the gene imposes severe practical limitations on simple genetic screening. Indeed, exon by exon sequencing of LDLR and other genes in each patient is the best screening genetic methods of choice. Although the hypercholesterolemia associated with FH can be controlled with cholesterol-lowering drug therapy (statins and other), patient response can vary quite widely.

Hipercolesterolemia familiar heterocigota: Revisión de las estrategias para su identificación y detección sistemática / Heterozygous familial hypercholesterolemia: Review strategies for identification and screening / Hipercolesterolemia familiar heterozigótica: Revisão das estratégias para sua identificação e detecção sistemática

La hipercolesterolemia familiar heterocigota (HFHe) es una enfermedad genética, común, autosómica dominante, causante de enfermedad cardíaca coronaria precoz. Si la HFHe es detectada y tratada en forma temprana, aquellos individuos afectados llegan a tener una expectativa de vida equivalente a las personas no afectadas. Diferentes estrategias existen para realizar una correcta identificación de los casos con HFHe; criterios fenotípicos, basados en niveles elevados de colesterol de lipoproteínas de baja densidad (C-LDL), estigmas clínicos (arco corneal, xantomas), sumados a antecedentes familiares de elevación del C-LDL y eventos cardiovasculares precoces son clásicamente utilizados en la práctica diaria. Por otro lado, existe la posibilidad de hacer diagnóstico genético de la HFHe y complementarlo con los aspectos y criterios fenotípicos. El desafío, una vez identificado el caso de HFHe, es implementar una estrategia de detección familiar, ya que por las características de heredabilidad mencionadas de la enfermedad, existe un cincuenta por ciento de probabilidad que un familiar directo padezca la enfermedad. El objetivo principal de esta revisión es presentar y discutir las diferentes estrategias de identificación y detección de pacientes con HFHe.

Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal dominant genetic disease, which causes premature coronary heart disease. If HeFH detected and treated early, those affected individuals have a life expectation equivalent to unaffected individuals. Different strategies exist to make a correct identification of cases with HeFH; phenotypic criteria, based on elevated levels of low density lipoprotein cholesterol (LDL-C), clinical stigmata (corneal arcus, xanthomas), together with a family history of elevated LDL-C and early cardiovascular events are conventionally used in daily practice. On the other hand there is the possibility of genetic diagnosis of HeFH and this is complemented with aspects and phenotypic criteria. Once identified HeFH case, the challenge is to implement a strategy of family screening, since the characteristics mentioned heritability of the disease, there is a fifty percent chance that a direct family member has the disease. The primary objective of this review is to present and discuss different strategies for the identification and detection of patients with HeFH.

A hipercolesterolemia familiar heterozigótica (HFHe) é uma doença genética comum, autossômica dominante, que causa a doença arterial coronariana precoce. Se HFHe é detectada e tratada precocemente, aqueles indivíduos afetados têm uma expectativa de vida equivalente a indivíduos não afetados. Existem diferentes estratégias para a identificação correta de casos com HFHe; critérios fenotípicos, baseados em níveis elevados de colesterol de lipoproteína de baixa densidade (C-LDL), estigmas clínicos (arco corneal, xantomas), juntamente com uma história familiar de elevados níveis de C-LDL e os eventos cardiovasculares precoces são convencionalmente utilizados na prática diária. Por outro lado, existe a possibilidade de realizar um diagnóstico genético da HFHe e esta é complementado com aspectos e critérios fenotípicos. Uma vez identificado o caso de HFHe, o desafio é implementar uma estratégia de triagem familiar, de acordo com as características mencionadas da hereditariedade da doença, existe uma chance de cinquenta por cento que um membro direto da família tem a doença. O principal objetivo desta revisão é apresentar e discutir estratégias diferentes para a identificação e detecção dos pacientes com HFHe.

Familial Hypercholesterolemia: Report of a Family.

We report a family, two sibling and mother, who developed corneal arcus and multiple skin lesions in form of xanthomas. The lesions appeared all over the body involving fingers, hands, elbows, knees, buttocks and feet. Laboratory studies showed total serum cholesterol level of >700 mg/dL; triglyceride level <150 mg/dL in all the cases. Father died few years back at a young age due to cardiac illness. Findings were consistent with homozygous familial hypercholesterolemia. In our country, incidence of hypercholesterolemia is not known. Only few case reports are there in the available literature.

Corneal arcus and xanthomas in homozygous familial hypercholesterolemia: First report from China.

We report the case of a 12-year-old male who developed corneal arcus and multiple skin lesions with a 10-year history of xanthomas. The lesions appeared over his fingers, hands, elbows, knees, buttocks and feet. Laboratory studies showed a total serum cholesterol level of 752.1 mg/dL; a triglyceride level of 96.6 mg/dL; a low-density lipoprotein cholesterol level of 661.3 mg/dL. Findings were consistent with homozygous familial hypercholesterolemia. To our knowledge, this is the first such case to be reported from China.