Joana Rita Chora1, Ana Catarina Alves1, Ana Margarida Medeiros1, Cibelle Mariano1, Goreti Lobarinhas2, António Guerra3, Helena Mansilha4, Helena Cortez-Pinto5, Mafalda Bourbon6. 1. Unidade I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; University of Lisboa, Faculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, Campo Grande, Lisboa, Portugal. 2. Serviço de Pediatria, Hospital de Santa Maria Maior, Barcelos, Portugal. 3. Serviço de Pediatria, Centro Hospitalar de São João, Porto, Portugal; Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS), Faculdade de Medicina, Universidade do Porto, Porto, Portugal. 4. Serviço de Pediatria/Nutrição Pediátrica, Departamento da Infância e Adolescência, Centro Materno-Infantil do Norte (CMIN), Porto, Portugal. 5. Departamento de Gastrenterologia, Laboratório de Nutrição, Hospital Santa Maria, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. 6. Unidade I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; University of Lisboa, Faculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, Campo Grande, Lisboa, Portugal. Electronic address: mafalda.bourbon@insa.min-saude.pt.
Abstract
BACKGROUND: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder and an unrecognized cause of dyslipidemia. Patients usually present with dyslipidemia and altered liver function and mutations in LIPA gene are the underlying cause of LALD. OBJECTIVE: The aim of this study was to investigate LALD in individuals with severe dyslipidemia and/or liver steatosis. METHODS: Coding, splice regions, and promoter region of LIPA were sequenced by Sanger sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH) patients (n = 492) and in a population sample comprising individuals with several types of dyslipidemia and/or liver steatosis (n = 258). RESULTS: This study led to the identification of LALD in 4 children referred to the Portuguese FH Study, all with a clinical diagnosis of FH. Mild liver dysfunction was present at the age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults at the time of referral have been identified with LALD. CONCLUSION: LALD is a life-threatening disorder, and early identification is crucial for the implementation of specific treatment to avoid premature mortality. FH cohorts should be investigated to identify possible LALD patients, who will need appropriate treatment. These results highlight the importance of correctly identifying the etiology of the dyslipidemia.
BACKGROUND:Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder and an unrecognized cause of dyslipidemia. Patients usually present with dyslipidemia and altered liver function and mutations in LIPA gene are the underlying cause of LALD. OBJECTIVE: The aim of this study was to investigate LALD in individuals with severe dyslipidemia and/or liver steatosis. METHODS: Coding, splice regions, and promoter region of LIPA were sequenced by Sanger sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH) patients (n = 492) and in a population sample comprising individuals with several types of dyslipidemia and/or liver steatosis (n = 258). RESULTS: This study led to the identification of LALD in 4 children referred to the Portuguese FH Study, all with a clinical diagnosis of FH. Mild liver dysfunction was present at the age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults at the time of referral have been identified with LALD. CONCLUSION: LALD is a life-threatening disorder, and early identification is crucial for the implementation of specific treatment to avoid premature mortality. FH cohorts should be investigated to identify possible LALD patients, who will need appropriate treatment. These results highlight the importance of correctly identifying the etiology of the dyslipidemia.
Authors: Ron C Helderman; Daniel G Whitney; Madalina Duta-Mare; Alena Akhmetshina; Nemanja Vujic; Shobana Jayapalan; Jeffry S Nyman; Biswapriya B Misra; Clifford J Rosen; Michael P Czech; Dagmar Kratky; Elizabeth Rendina-Ruedy Journal: Bone Date: 2021-04-07 Impact factor: 4.626
Authors: Jacqueline S Dron; Jian Wang; Adam D McIntyre; Michael A Iacocca; John F Robinson; Matthew R Ban; Henian Cao; Robert A Hegele Journal: BMC Med Genomics Date: 2020-02-10 Impact factor: 3.063