RESUMEN
UNLABELLED: 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 â¼3%-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 â¼1 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% confidence interval [CI]: 51%-69%) of reported mutations among multiethnic CESD patients. Using this estimate, the predicted prevalence of CESD in the Caucasian and Hispanic populations is â¼0.8 per 100,000 (â¼1 in 130,000; 95% CI: â¼1 in 90,000 to 1 in 170,000). CONCLUSION: These data indicate that CESD may be underdiagnosed 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.
Asunto(s)
Enfermedad de Acumulación de Colesterol Éster/etnología , Enfermedad de Acumulación de Colesterol Éster/genética , Etnicidad/etnología , Etnicidad/genética , Mutación/genética , Esterol Esterasa/genética , Adolescente , Adulto , Negro o Afroamericano/etnología , Negro o Afroamericano/genética , Anciano , Anciano de 80 o más Años , Asiático/etnología , Asiático/genética , Exones/genética , Heterocigoto , Hispánicos o Latinos/etnología , Hispánicos o Latinos/genética , Humanos , Judíos/etnología , Judíos/genética , Persona de Mediana Edad , New York , Prevalencia , Estudios Retrospectivos , Población Blanca/etnología , Población Blanca/genética , Adulto JovenRESUMEN
This case describes a patient with cholesteryl ester storage disease who underwent liver transplantation for progressive cirrhosis, portal hypertension, ascites, and uncontrollable gastrointestinal bleeding. Four and one-half years posttransplant, her growth improved, cholesterol levels have returned to normal, and she is clinically well except for mild hypersplenism and an elevated blood urea nitrogen (BUN) and creatinine. Serum triglycerides remain elevated, but there have been no signs of progressive renal, intestinal, vascular, or pulmonary disease.