Large-scale screening of lipase acid deficiency in at risk population.
Acid lipase deficiency
CESD
Cholesterol ester storage disease
DBS
Dried blood spot
LAL
Screening
Wolman
Journal
Clinica chimica acta; international journal of clinical chemistry
ISSN: 1873-3492
Titre abrégé: Clin Chim Acta
Pays: Netherlands
ID NLM: 1302422
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
26
02
2021
revised:
07
04
2021
accepted:
08
04
2021
pubmed:
16
4
2021
medline:
22
6
2021
entrez:
15
4
2021
Statut:
ppublish
Résumé
Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD). This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots. LAL activity was lower than 0.05 nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel. This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations.
Sections du résumé
BACKGROUND
BACKGROUND
Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD).
METHODS
METHODS
This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots.
RESULTS
RESULTS
LAL activity was lower than 0.05 nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel.
CONCLUSION
CONCLUSIONS
This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations.
Identifiants
pubmed: 33857477
pii: S0009-8981(21)00121-2
doi: 10.1016/j.cca.2021.04.005
pii:
doi:
Substances chimiques
Cholesterol Esters
0
Sterol Esterase
EC 3.1.1.13
Lipase
EC 3.1.1.3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-69Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.