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

Date

2022

Authors

Topham, Emily
Roy, Sani
Hamilton, Luke
Wilson, Don

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Introduction: 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). 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 (2,4). Case Presentation 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 (BMI < 5th percentile, TC 319, HDL-C 65, TG 71, Non-HDL-C 254). 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 (LDL-C 161). 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, he had hypercholesterolemia with LDL-C of 198 mg/dL (BMI >99th percentile, TC 274, HDL-C 41, TG 176, Non-HDL-C 233). 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 Type 1 diabetes 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. Discussion & Conclusion: The development of CVD in individuals with PWS is complex and risk factors are often underdiagnosed. Inherent to PWS are hypotonia and decreased muscle mass, leading to a 20% lower basal metabolic rate and decreased exercise tolerance. Combined with the development of insatiable appetite and hyperphagia, these factors often lead to cardiovascular disease risk (5). In adults with PWS, hypercholesterolemia was undiagnosed in 6%, T2D in 5%, hypertension in 3% (5). Risk factors associated with PWS contribute to premature mortality in this population and 70% die at a young age (29 ± 16 years) (1). 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.

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