Genetics
Children with Prader-Willi syndrome have markedly higher Lp(a) and hs-CRP than controls, with the deletion genetic subtype most affected, 32-patient study finds (J Endocr Soc 2025)
Original title: Serum Lipoprotein(a) and High-Sensitivity C-reactive Protein Correlate With Somatic Parameters Including MLPA Subgroups in Children With Prader-Willi Syndrome
This study compared 32 genetically confirmed, growth-hormone-treatment-naive children with Prader-Willi syndrome (PWS), a chromosome 15q11-13 disorder causing syndromic childhood obesity, against 20 children with simple obesity and 20 healthy age-matched controls, measuring serum Lp(a) and high-sensitivity CRP alongside body composition, sleep apnoea and hepatic elastography. Lp(a) was significantly higher in the PWS group than controls (P < .0001), with no difference between the two control groups, while Lp(a) itself did not correlate with body weight, BMI or waist circumference. hs-CRP was also elevated in PWS versus both control groups. Lower fat-free mass index correlated with higher Lp(a) (r = -0.5525, P = .001) but not with hs-CRP. When PWS patients were split into deletion and non-deletion genetic subtypes, the deletion subgroup showed significantly more altered Lp(a), hs-CRP, fat-free mass and sleep apnoea parameters. The authors conclude Lp(a) and hs-CRP are core, genotype-linked independent risk markers in PWS, particularly in the deletion subtype, supporting genetic subtyping to guide future targeted therapeutics.
Original abstract
Context: Prader-Willi syndrome (PWS) is 1 of the most common monochromosomal (15q11-13) causes of polygenic syndromic childhood obesity.
Objectives: We primarily compare and correlate serum lipoprotein(a) [Lp(a)], high-sensitivity C-reactive protein (hs-CRP), and baseline clinical characteristics of genetically confirmed children with PWS at their GH treatment-naïve stage to their control groups. Secondary objectives were to correlate serum Lp(a) and hs-CRP concentration to multiplex ligation-dependent probe amplification subgroups, body composition indices, sleep apnea parameters, and hepatic shear-stress by 2-dimensional shear wave elastography in children with PWS.
Methods: A total of 32 genetically confirmed PWS children (age 5 to 18 years), 20 simple obesity children, and 20 healthy children as age-matched control groups were studied for the primary and secondary study objectives.
Results: Lp(a) was higher in the study group as compared to the control group (P < .0001), but we found no difference between the control groups (P = .9680).In addition, no correlation was detected in Lp(a) levels in the study population with respect to their body weight, body mass index, and waist circumference. hs-CRP levels were also higher in the study population compared to both control groups (P = .0962; P < .0001); in contrast, Lp(a) differed significantly between the control groups (P = .002). Lower fat-free mass index (FFMI) correlated with higher levels of serum Lp(a) (r = -0.5525; P = .001), whereas FFMI was not correlated with hs-CRP levels in PWS children (P = .657). Based on genomic subtypes, patients with PWS were divided into deletion and nondeletion genetic subgroups. We found significantly altered levels of Lp(a), hs-CRP, fat-free mass, and sleep apnea parameters, particularly in the deletion subgroup.
Conclusion: Serum Lp(a) as well as hs-CRP stand out to be the core independent risk factors along with their strong correlation with the other study parameters, which necessitates the role of future targeted therapeutics in PWS, especially in deletion pathology. Thus, genetic subtyping during diagnostic confirmation endorses further prognostic elaboration.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.