Novel LIPA mutations in Mexican siblings with lysosomal acid lipase deficiency  

作　　者：Yuritzi Santillán-Hernández Enory Almanza-Miranda Winnie W Xin Kendrick Goss Aurea Vera-Loaiza María T Gorráez-de la Mora Raul E Pina-Aguilar 

机构地区：[1]Medical Genetics Department,Centro Médico Nacional "20 de Noviembre",ISSSTE,México City 03100,México [2]Pediatric Gastroenterology Department,Centro Médico Nacional "20 de Noviembre",ISSSTE,México City 03229,México [3]Neurogenetics DNA Diagnostic Laboratory,Massachusetts General Hospital,Boston,MA 02114,United States [4]Pathology Department,Centro Médico Nacional "20 de Noviembre",ISSSTE,México City 03229,México [5]Medical Genomics Division,Centro Médico Nacional "20 de Noviembre",ISSSTE,México City 03100,México

出　　处：《World Journal of Gastroenterology》2015年第3期1001-1008,共8页世界胃肠病学杂志（英文版）

摘　　要：Lysosomal acid lipase(LAL) deficiency is an underrecognized lysosomal disease caused by deficient enzymatic activity of LAL.In this report we describe two affected female Mexican siblings with early hepatic complications.At two months of age,the first sibling presented with alternating episodes of diarrhea and constipation,and later with hepatomegaly,elevated transaminases,high levels of total and low-density lipoprotein cholesterol,and low levels of highdensity lipoprotein.Portal hypertension and grade 2 esophageal varices were detected at four years of age.The second sibling presented with hepatomegaly,elevated transaminases and mildly elevated lowdensity lipoprotein and low high-density lipoprotein at six months of age.LAL activity was deficient in both patients.Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4:c.253C>A and c.294C>G.These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease,and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.Lysosomal acid lipase(LAL) deficiency is an underrecognized lysosomal disease caused by deficient enzymatic activity of LAL.In this report we describe two affected female Mexican siblings with early hepatic complications.At two months of age,the first sibling presented with alternating episodes of diarrhea and constipation,and later with hepatomegaly,elevated transaminases,high levels of total and low-density lipoprotein cholesterol,and low levels of highdensity lipoprotein.Portal hypertension and grade 2 esophageal varices were detected at four years of age.The second sibling presented with hepatomegaly,elevated transaminases and mildly elevated lowdensity lipoprotein and low high-density lipoprotein at six months of age.LAL activity was deficient in both patients.Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4:c.253C>A and c.294C>G.These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease,and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.

关 键 词：Cholesteryl ester storage disease Liver fibrosis DYSLIPIDEMIA Liver steatosis Wolman disease 

分 类 号：R575[医药卫生—消化系统] R589[医药卫生—内科学]