533例原发性肥大性骨关节病患者三种临床亚型的不同特征。

Distinct features of three clinical subtypes in 533 patients with primary hypertrophic osteoarthropathy.

作者信息

Cai Xilei, Yang Xiujuan, Zhang Pengyue, Dou Ziyue, Chen Zilian, Zhu Chongzhi, Xu Weiwei, Wang Xinchen, Hong Xiaodan, Zhang Zhenhua

机构信息

Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, Furong Road 678, Hefei, 230601, China.

Institute of Clinical Virology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Orphanet J Rare Dis. 2025 Apr 18;20(1):188. doi: 10.1186/s13023-025-03722-3.

DOI:10.1186/s13023-025-03722-3

PMID:40251683

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12007382/

Abstract

BACKGROUND

Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disorder classified into clinical subtypes and genetic subtypes. Previous clinical studies have primarily focused on case reports and family analyses, largely characterizing the genetic subtypes. However, there remains a long-standing gap in understanding the characteristics of the different clinical subtypes of PHO. This study aimed to determine the distribution of the three clinical subtypes of PHO and compare their clinical characteristics using a large global sample.

METHODS

A systematic literature search was conducted in multiple databases to categorize cases into complete form (CO), incomplete form (IN), and fruste form (FR). Statistical analyses were performed to assess clinical differences in a retrospective study design.

RESULTS

Males predominated across all subtypes, whereas females were most prevalent in IN patients (51.1%). IN patients had the highest family history rate (62.1%). Age at onset peaked in adolescence for CO and FR patients, while IN patients exhibited bimodal peaks in early childhood and adolescence. Congenital diseases were more frequent in IN patients (7.8%, P = 0.021), while CO patients had a higher prevalence of digestive system diseases (12.2%, P = 0.007). Urinary prostaglandin E2 (PGE2) and PGE Metabolite (PGEM) were consistently elevated in CO and FR patients. In IN patients, urinary PGE2 levels were also increased, but the urinary PGEM levels showed equal proportions of elevation and reduction. Genetic analysis revealed that solute carrier organic anion transporter family member 2A1 (SLCO2A1) mutations were predominant in CO (95 cases, 73.1%) and FR (22 cases, 57.9%) patients, whereas hydroxyprostaglandin dehydrogenase (HPGD) mutations were most frequently associated with IN (25 cases, 73.5%).

CONCLUSIONS

The three clinical subtypes of PHO exhibited distinct characteristics with no clear correlation between clinical and genetic subtypes. These findings highlighted the clinical significance of PHO typing and provided valuable insights for diagnosis, differential diagnosis and subtype-specific management strategies.

摘要

背景

原发性肥厚性骨关节病（PHO）是一种罕见的遗传性疾病，分为临床亚型和遗传亚型。以往的临床研究主要集中在病例报告和家系分析上，主要对遗传亚型进行了特征描述。然而，在理解PHO不同临床亚型的特征方面，仍然存在长期的差距。本研究旨在确定PHO三种临床亚型的分布情况，并使用大量全球样本比较它们的临床特征。

方法

在多个数据库中进行系统的文献检索，将病例分为完全型（CO）、不完全型（IN）和顿挫型（FR）。在回顾性研究设计中进行统计分析，以评估临床差异。

结果

所有亚型中男性占主导地位，而女性在IN患者中最为常见（51.1%）。IN患者的家族史发生率最高（62.1%）。CO和FR患者的发病年龄在青春期达到峰值，而IN患者在幼儿期和青春期表现出双峰。先天性疾病在IN患者中更为常见（7.8%，P = 0.021），而CO患者消化系统疾病的患病率较高（12.2%，P = 0.007）。CO和FR患者的尿前列腺素E2（PGE2）和PGE代谢物（PGEM）持续升高。在IN患者中，尿PGE2水平也升高，但尿PGEM水平升高和降低的比例相当。基因分析显示，溶质载体有机阴离子转运体家族成员2A1（SLCO2A1）突变在CO（95例，73.1%）和FR（22例，57.9%）患者中占主导地位，而羟基前列腺素脱氢酶（HPGD）突变最常与IN（25例，73.5%）相关。