title: Novel LIPA mutations in Mexican siblings with lysosomal acid lipase deficiency.
abstract: Lysosomal acid lipase (LAL) deficiency is an under-recognized 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 high-density 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 low-density 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.
authors.affiliation: Yuritzi Santillán-Hernández, Aurea Vera-Loaiza, Medical Genetics Department, Centro Médico Nacional "20 de Noviembre", ISSSTE, México City 03100, México.
authors.forename: Yuritzi
authors.initials: Y
authors.lastname: Santillán-Hernández
authors.affiliation: Yuritzi Santillán-Hernández, Aurea Vera-Loaiza, Medical Genetics Department, Centro Médico Nacional "20 de Noviembre", ISSSTE, México City 03100, México.
authors.forename: Enory
authors.initials: E
authors.lastname: Almanza-Miranda
authors.affiliation: Yuritzi Santillán-Hernández, Aurea Vera-Loaiza, Medical Genetics Department, Centro Médico Nacional "20 de Noviembre", ISSSTE, México City 03100, México.
authors.forename: Winnie W
authors.initials: WW
authors.lastname: Xin
authors.affiliation: Yuritzi Santillán-Hernández, Aurea Vera-Loaiza, Medical Genetics Department, Centro Médico Nacional "20 de Noviembre", ISSSTE, México City 03100, México.
authors.forename: Kendrick
authors.initials: K
authors.lastname: Goss
authors.affiliation: Yuritzi Santillán-Hernández, Aurea Vera-Loaiza, Medical Genetics Department, Centro Médico Nacional "20 de Noviembre", ISSSTE, México City 03100, México.
authors.forename: Aurea
authors.initials: A
authors.lastname: Vera-Loaiza
authors.affiliation: Yuritzi Santillán-Hernández, Aurea Vera-Loaiza, Medical Genetics Department, Centro Médico Nacional "20 de Noviembre", ISSSTE, México City 03100, México.
authors.forename: María T
authors.initials: MT
authors.lastname: Gorráez-de la Mora
authors.affiliation: Yuritzi Santillán-Hernández, Aurea Vera-Loaiza, Medical Genetics Department, Centro Médico Nacional "20 de Noviembre", ISSSTE, México City 03100, México.
authors.forename: Raul E
authors.initials: RE
authors.lastname: Piña-Aguilar
mesh_terms: D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004932:Esophageal and Gastric Varices / Q000201:enzymology / Q000235:genetics; D004945:Esophagoscopy; D005091:Exons; D005234:Fatty Liver / Q000201:enzymology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006529:Hepatomegaly / Q000201:enzymology / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D006975:Hypertension, Portal / Q000201:enzymology / Q000235:genetics; D007150:Immunohistochemistry; D007223:Infant; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics; D008800:Mexico; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D035781:Siblings / Q000208:ethnology; D002787:Sterol Esterase / Q000172:deficiency* / Q000235:genetics*; D013997:Time Factors; D018615:Ultrasonography, Doppler, Color; D015223:Wolman Disease / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*
chemical_list: C503451:LIPA protein, human; D002787:Sterol Esterase
keywords: Cholesteryl ester storage disease; Dyslipidemia; Liver fibrosis; Liver steatosis; Wolman disease