Frequency of the cholesteryl ester storage disease commonLIPAE8SJM mutation (c.894G>A) in various racial and ethnic groups

Abstract

Cholesteryl Ester Storage Disease (CESD) and Wolman disease are autosomal recessive later-onset and severe infantile disorders, respectively, which result from the deficient activity of lysosomal acid lipase (LAL). LAL is encoded by LIPA (10q23.31) and the most common mutation associated with CESD is an exon 8 splice junction mutation (c.894G>A; E8SJM), which expresses only ~3–5% of normally spliced LAL. However, the frequency of c.894G>A is unknown in most populations. To estimate the prevalence of CESD in different populations, the frequencies of the c.894G>A mutation were determined in 10,000 LIPA alleles from healthy African-American, Asian, Caucasian, Hispanic and Ashkenazi Jewish individuals from the greater New York metropolitan area and 6,578 LIPA alleles from African-American, Caucasian, and Hispanic subjects enrolled in the Dallas Heart Study. The combined c.894G>A allele frequencies from the two cohorts ranged from 0.0005 (Asian) to 0.0017 (Caucasian and Hispanic), which translated to carrier frequencies of 1 in 1,000 to ~1 in 300, respectively. No African-American heterozygotes were detected. Additionally, by surveying the available literature, c.894G>A was estimated to account for 60% (95% CI: 51%–69%) of reported mutations among multi-ethnic CESD patients. Using this estimate, the predicted prevalence of CESD in the Caucasian and Hispanic populations is ~0.8 per 100,000 (~1 in 130,000; 95% CI: ~1 in 90,000 to 1 in 170,000). Conclusion These data indicate that CESD may be under-diagnosed in the general Caucasian and Hispanic populations, which is important since clinical trials of enzyme replacement therapy for LAL deficiency are currently being developed. Moreover, future studies on CESD prevalence in African and Asian populations may require full-gene LIPA sequencing to determine heterozygote frequencies since c.894G>A is not common in these racial groups.

Lysosomal Acid Lipase Deficiency Unmasked in Two Children With Nonalcoholic Fatty Liver Disease

“…It is now recognized that LAL-D may be both underdiagnosed 2 and associated with significant morbidity and mortality, even among pediatric and adolescent patients. In a literature review, Bernstein et al 3 …”

Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An update

“…Thus, prevalence may be expected to be 1:40 000 German newborn infants, and 1:300 000 Hispanics and Caucasians. 19,20 The number of reported cases has been much lower than these estimates, which suggests a non-specific clinical course and the absence of a characteristic phenotype. No studies have been conducted regarding the prevalence of LAL-D in Argentina.…”

The Disease Is the Accumulation of Cholesterol Esters Due to Deficit of Lysosomal Acid Lipase. Clinical Case of Lysosomal Acid Lipase Deficiency Is Described in This Article

“…Такие метаболические нару-шения сопровождаются повышением общего уровня холестерина, холестерина липопротеинов низкой плот-ности и триглицеридов в сыворотке крови, а также сни-жением холестерина липопротеинов высокой плотности в сыворотке крови, т. е. диагнозом «дислипидемия IIb-типа». Повы шен ное содержание холестерина липо-протеинов низкой плотности вызывает ускоренное раз-витие атеросклероза; имеются сообщения о пациентах с БНЭХ с ранним атеросклерозом, ишемией, инсультами и операциями коронарного шунтирования [1,3,5].…”