Rahman Qaddra Fahada Ab, Jufri Nurul Farhana, Hamid Asmah
Biomedical Science Program, Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Intractable Rare Dis Res. 2023 Feb;12(1):5-12. doi: 10.5582/irdr.2022.01127.
Prader-Willi syndrome (PWS) is a rare genetic disorder due to lack of genes expression inherited from the paternal chromosome 15q11-q13 region usually from paternal deletions, maternal uniparental disomy 15 or imprinting defect. There are two different nutritional stages reported in an individual with PWS; first stage during infancy marked by feeding and growth difficulties and second stage where hyperphagia starts and leads to development of obesity. However, the exact mechanism of hyperphagia development, from having difficulties in feeding during early years to insatiable appetite after they grow is still unknown and is the focused in this review. The keywords used for literature search such as "Prader-Willi syndrome", "hyperphagia", "obesity", and "treatment" were used to create the search strings by using synonyms in order to retrieve the relevant records from PubMed, Scopus and Science Direct. The possible mechanism of hyperphagia can be classed into hormonal abnormalities such as increase in ghrelin and leptin from infancy to adulthood. Low level of hormones was observed in the thyroid, insulin and peptide YY at certain ages. Neuronal abnormalities contributed by Orexin A and brain structure alteration was documented at 4-30 years old. Treatment in the form of drugs such as livoletide, topiramate, and diazoxide could potentially alleviate these abnormalities and make hyperphagia less prominent in PWS. The approaches are important to regulate the hormonal changes and neuronal involvement as potentially controlling hyperphagia and obesity.
普拉德-威利综合征（PWS）是一种罕见的遗传性疾病，由于缺乏从父本染色体15q11-q13区域遗传的基因表达，通常源于父本缺失、母本单亲二体15或印记缺陷。据报道，患有PWS的个体存在两个不同的营养阶段；第一阶段是婴儿期，其特征是喂养和生长困难，第二阶段是食欲亢进开始并导致肥胖的发展。然而，从早年喂养困难到长大后食欲亢进的确切机制仍然未知，这也是本综述的重点。用于文献检索的关键词，如“普拉德-威利综合征”、“食欲亢进”、“肥胖”和“治疗”，通过使用同义词来创建检索词，以便从PubMed、Scopus和Science Direct中检索相关记录。食欲亢进的可能机制可分为激素异常，如从婴儿期到成年期胃饥饿素和瘦素增加。在某些年龄段观察到甲状腺、胰岛素和肽YY激素水平较低。在4至30岁时记录到食欲素A和脑结构改变导致的神经元异常。诸如利沃来肽、托吡酯和二氮嗪等药物形式的治疗可能会减轻这些异常，并使PWS患者的食欲亢进不那么明显。这些方法对于调节激素变化和神经元参与很重要，因为它们有可能控制食欲亢进和肥胖。
