title: Lysosomal Acid Lipase Deficiency in 23 Spanish Patients: High Frequency of the Novel c.966+2T>G Mutation in Wolman Disease.
abstract: Lysosomal acid lipase (LAL) is a lysosomal key enzyme involved in the intracellular hydrolysis of cholesteryl esters and triglycerides. Patients with very low residual LAL activity present with the infantile severe form Wolman disease (WD), while patients with some residual activity develop the less severe disorder known as Cholesteryl ester storage disorder (CESD). We present the clinical, biochemical, and molecular findings of 23 Spanish patients (22 families) with LAL deficiency. We identified eight different mutations, four of them not previously reported. The novel c.966+2T>G mutation accounted for 75% of the Wolman disease alleles, and the frequent CESD associated c.894G>A mutation accounted for 55% of the CESD alleles in our cohort. Haplotype analysis showed that both mutations co-segregated with a unique haplotype suggesting a common ancestor. Our study contributes to the LAL deficiency acknowledgement with novel mutations and with high frequencies of some unknown mutations for WD.
authors.affiliation: Errors Congènits del Metabolisme-IBC, Serv. Bioquímica i Genètica Molecular, CDB, Hospital Clínic, C/Mejía Lequerica, s/n, Edifici Helios III, Barcelona, 08028, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Ruiz-Andrés
authors.affiliation: Errors Congènits del Metabolisme-IBC, Serv. Bioquímica i Genètica Molecular, CDB, Hospital Clínic, C/Mejía Lequerica, s/n, Edifici Helios III, Barcelona, 08028, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Sellés
authors.affiliation: Errors Congènits del Metabolisme-IBC, Serv. Bioquímica i Genètica Molecular, CDB, Hospital Clínic, C/Mejía Lequerica, s/n, Edifici Helios III, Barcelona, 08028, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras and IDIBAPS, Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Arias
authors.affiliation: Errors Congènits del Metabolisme-IBC, Serv. Bioquímica i Genètica Molecular, CDB, Hospital Clínic, C/Mejía Lequerica, s/n, Edifici Helios III, Barcelona, 08028, Spain. lgort@clinic.ub.es.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras and IDIBAPS, Barcelona, Spain. lgort@clinic.ub.es.
authors.forename: Laura
authors.initials: L
authors.lastname: Gort
keywords: CESD; Cholesteryl ester storage disorder; Haplotype analysis; LAL deficiency; LIPA gene; Mutation; Wolman disease