TY - JOUR
T1 - Initial assessment and ongoing monitoring of lysosomal acid lipase deficiency in children and adults
T2 - Consensus recommendations from an international collaborative working group
AU - Kohli, Rohit
AU - Ratziu, Vlad
AU - Fiel, Maria Isabel
AU - Waldmann, Elisa
AU - Wilson, Don P.
AU - Balwani, Manisha
N1 - Funding Information:
Editorial and medical writing support was provided by Illyce Nuñez, PhD and Michael D. Morren, RPh, MBA of Peloton Advantage, LLC, an OPEN Health company, and was funded by Alexion Pharmaceuticals, Inc . The meeting that served as the basis for these recommendations was planned and funded by Alexion Pharmaceuticals, Inc. All attendees received reimbursement for travel and accommodation-related costs for their participation. Alexion provided review of this manuscript for the authors' consideration.
Funding Information:
R. Kohli has participated in advisory boards and served as a consultant for Alexion Pharmaceuticals, Inc. V. Ratziu has participated in advisory boards and served as a consultant for Alexion Pharmaceuticals, Inc. M. I. Fiel has participated in advisory boards for Alexion Pharmaceuticals, Inc., and has received research funding from Alexion Pharmaceuticals, Inc. E. Waldmann has participated in advisory boards for Alexion Pharmaceuticals, Inc. and received honoraria from Berlin-Chemie, Amgen, and Sanofi. D. P. Wilson has been a speaker for the Osler Institute and the National Lipid Association, Insulet Corp., and Alexion Pharmaceuticals, Inc.; has participated in advisory boards for Aegerion Pharmaceuticals, Alexion Pharmaceuticals, Inc., Merck Sharp & Dohme, and Novo Nordisk Inc.; has received research funding from Merck Sharp & Dohme and Novo Nordisk Inc. and is a member of the International Lysosomal Acid Lipase Deficiency Registry scientific advisory board M. Balwani has participated in advisory boards for Alexion Pharmaceuticals, Inc. and is a member of the International Lysosomal Acid Lipase Deficiency Registry scientific advisory board.
Publisher Copyright:
© 2019
PY - 2020/2
Y1 - 2020/2
N2 - Background: Lysosomal acid lipase (LAL) deficiency is an ultra-rare, progressive, autosomal recessive disorder. Functional mutations in LIPA, the gene that encodes LAL, result in accumulation of cholesteryl esters and triglycerides in hepatocytes and in the macrophages of the intestines, vascular endothelial system, and numerous other organs. LAL deficiency has a broad clinical spectrum; children and adults can present with dyslipidemia, liver enzyme elevations, hepatosplenomegaly, hepatic steatosis, liver fibrosis and/or cirrhosis, and vascular disease, which may lead to significant morbidity and premature mortality in some patients. Given the systemic involvement and the wide range of healthcare specialists who manage patients with LAL deficiency, there is a need for guidelines to assess and monitor disease involvement. Objectives: To provide a set of recommendations for the initial assessment and ongoing monitoring of patients with LAL deficiency to help physicians in various disciplines effectively manage the disease based on the observed presentation and progression in each case. Methods: A group of internationally recognized healthcare specialists with expertise in clinical genetics, pathology, hepatology, gastroenterology, cardiology, and lipidology convened to develop an evidence-based consensus of best practices for the initial assessment and ongoing monitoring of children and adults with LAL deficiency, regardless of treatment status; infants with LAL deficiency have been excluded from these guidelines because they require specialized care. Results: The authors present guidance for the assessment and monitoring of patients with LAL deficiency based on age and disease manifestations that include the hepatic, cardiovascular, and gastrointestinal systems. A schedule for ongoing monitoring of disease progression is provided. In addition, the need to establish an interdisciplinary and integrated care team to optimize the approach to managing this systemic disease is highlighted. Conclusions: There is currently no published guidance on the assessment and monitoring of patients with LAL deficiency. These consensus recommendations for the initial assessment and ongoing monitoring of children and adults with LAL deficiency are intended to help improve the management of these patients.
AB - Background: Lysosomal acid lipase (LAL) deficiency is an ultra-rare, progressive, autosomal recessive disorder. Functional mutations in LIPA, the gene that encodes LAL, result in accumulation of cholesteryl esters and triglycerides in hepatocytes and in the macrophages of the intestines, vascular endothelial system, and numerous other organs. LAL deficiency has a broad clinical spectrum; children and adults can present with dyslipidemia, liver enzyme elevations, hepatosplenomegaly, hepatic steatosis, liver fibrosis and/or cirrhosis, and vascular disease, which may lead to significant morbidity and premature mortality in some patients. Given the systemic involvement and the wide range of healthcare specialists who manage patients with LAL deficiency, there is a need for guidelines to assess and monitor disease involvement. Objectives: To provide a set of recommendations for the initial assessment and ongoing monitoring of patients with LAL deficiency to help physicians in various disciplines effectively manage the disease based on the observed presentation and progression in each case. Methods: A group of internationally recognized healthcare specialists with expertise in clinical genetics, pathology, hepatology, gastroenterology, cardiology, and lipidology convened to develop an evidence-based consensus of best practices for the initial assessment and ongoing monitoring of children and adults with LAL deficiency, regardless of treatment status; infants with LAL deficiency have been excluded from these guidelines because they require specialized care. Results: The authors present guidance for the assessment and monitoring of patients with LAL deficiency based on age and disease manifestations that include the hepatic, cardiovascular, and gastrointestinal systems. A schedule for ongoing monitoring of disease progression is provided. In addition, the need to establish an interdisciplinary and integrated care team to optimize the approach to managing this systemic disease is highlighted. Conclusions: There is currently no published guidance on the assessment and monitoring of patients with LAL deficiency. These consensus recommendations for the initial assessment and ongoing monitoring of children and adults with LAL deficiency are intended to help improve the management of these patients.
KW - Cirrhosis
KW - Dyslipidemia
KW - Expert opinion
KW - Fibrosis
KW - Patient monitoring
KW - Practice recommendations
UR - http://www.scopus.com/inward/record.url?scp=85076522752&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2019.11.004
DO - 10.1016/j.ymgme.2019.11.004
M3 - Review article
C2 - 31767214
AN - SCOPUS:85076522752
SN - 1096-7192
VL - 129
SP - 59
EP - 66
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 2
ER -