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Lysosomal Acid Lipase Deficiency in 23 Spanish Patients: High Frequency of the Novel c.966+2T>G Mutation in Wolman Disease

  • Carla Ruiz-Andrés
  • Elena Sellés
  • Angela Arias
  • Laura Gort
  • The Spanish LAL Deficiency Working Group
Research Report
Part of the JIMD Reports book series (JIMD, volume 37)

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.

Keywords

CESD Cholesteryl ester storage disorder Haplotype analysis LAL deficiency LIPA gene Mutation Wolman disease 

Notes

Acknowledgments

The authors declare no conflict of interest. The authors want to thank all the physicians who referred the samples of the patients. The authors also thank Dr. A. Chabás for biochemical diagnosis done before 2008 and J. Jarque for excellent technical assistance.

The CIBER of Enfermedades Raras (CIBERER) is an initiative of the ISCIII.

CERCA Programme/Generalitat de Catalunya.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Carla Ruiz-Andrés
    • 1
  • Elena Sellés
    • 1
  • Angela Arias
    • 1
    • 2
  • Laura Gort
    • 1
    • 2
  • The Spanish LAL Deficiency Working Group
  1. 1.Errors Congènits del Metabolisme-IBC, Serv. Bioquímica i Genètica Molecular, CDB, Hospital ClínicBarcelonaSpain
  2. 2.CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras and IDIBAPSBarcelonaSpain

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