†Does Cholesterol Screening in Prader Willi Syndrome Represent an Opportunity to Reduce Cardiovascular Disease Risk?

Abstract

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis Hypercholesterolemia is a significant cause of cardiovascular disease (CVD) worldwide. Hypercholesterolemia screening guidelines include an initial lipid panel starting at 2 years-of-age with risk factors and 10 years-of-age for all children, regardless of risk status ( 3 Grundy S.M. et al. Journal of the American College of Cardiology. 2019; 73: e285-e350 Crossref PubMed Scopus (1054) Google Scholar ). Children with PWS develop a variety of health conditions, increasing their risk of premature CVD. Thus, this population should undergo global risk factor assessment, including cholesterol screening, starting at 2 years. In 2019, the American Academy of Pediatrics management guidelines for PWS included an initial lipid panel from ages 1-5 years ( 2 Duis J. et al. Molecular Genetics and Genomic Medicine. 2019; 7: e514 Crossref PubMed Scopus (29) Google Scholar , 4 McCandless SE. Pediatrics. 2011; 127: 195-204 Crossref PubMed Scopus (122) Google Scholar ). Objective/Purpose Case 1: A full-term male infant was admitted to the NICU for hypotonia and difficulty feeding. PWS was diagnosed by microarray paternal deletion of 15q11.2-q13. At age 3 months, growth hormone was started. He developed significant hypercholesterolemia with LDL-C of 236 mg/dL at 3.5 years (Table 1). His father has hypercholesterolemia. Familial hypercholesterolemia (FH) genetic screening was negative. Renal, hepatic function and HbA1c were normal. At 3.5 years, a low normal T4 with inappropriately normal TSH was found and consistent with partial central hypothyroidism. He was treated with levothyroxine which normalized his T4; while the LDL-C improved but remained elevated. Statin therapy was deferred due to young age. Case 2: A male infant was admitted to the NICU for hypotonia and difficulty feeding. Methylation study confirmed PWS. At 5.5 years, BMI was >99th percentile and he had hypercholesterolemia. LDL-C was 198 mg/dL (Table 2). Neither parent is known to have hypercholesterolemia. FH genetic screening was negative. Thyroid and renal function were normal; however, transaminases were very elevated without cholestasis. At 7.5 years, a statin was recommended but the family opted for ezetimibe. At age 9 years, he developed HbA1c of 11.1%, and had negative antibodies consistent with Type 2 Diabetes Mellitus (T2D). He was treated with diet, insulin, and metformin. As HbA1c normalized (5.5%), the medications were discontinued. Methods N/A. Results N/A Conclusions In adults with PWS, hypercholesterolemia was undiagnosed in 6%, T2D in 5%, and hypertension in 3% ( 5 Pellikaan K. et al. The Journal of Clinical Endocrinology & Metabolism. 2020; 105: e4671-e4687 Crossref Scopus (24) Google Scholar ). Risk factors associated with PWS contribute to premature mortality in this population and 70% die at a young age (29 +/- 16 years) ( 1 Butler M.G. et al. Genetics in Medicine. 2017; 19: 635-642 Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar ). The presence of hypercholesterolemia or other risk factors, especially those present from an early age, greatly enhance future CVD-related risk, and represents a need for screening. Nothing to disclose.