Department of Pediatrics, Division of Pediatric Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Albright Clinic, Kennedy Krieger Institute, Baltimore, Maryland.
J Clin Endocrinol Metab. 2018 Jan 1;103(1):158-168. doi: 10.1210/jc.2017-00860.
Albright hereditary osteodystrophy (AHO) is caused by heterozygous inactivating mutations in GNAS. Depending on the parental origin of the mutated allele, patients develop either pseudohypoparathyroidism type 1A (PHP1A), with multihormone resistance and severe obesity, or pseudopseudohypoparathyroidism (PPHP), without hormonal abnormalities or marked obesity. Subcutaneous ossifications (SCOs) are a source of substantial morbidity in both PHP1A and PPHP.
This study investigated the previously undetermined prevalence of SCO formation in PHP1A vs PPHP as well as possible correlations with genotype, sex, age, hormonal resistance, and body mass index (BMI).
This study evaluated patients with AHO for SCOs by physical examination performed by one consistent physician over 16 years.
Albright Clinic, Kennedy Krieger Institute; Institute for Clinical and Translational Research, Johns Hopkins Hospital; Albright Center, Connecticut Children's Medical Center.
We evaluated 67 patients with AHO (49 with PHP1A, 18 with PPHP) with documented mutations in GNAS.
Relationships of SCOs to genotype, sex, age, hormonal resistance, and BMI.
Forty-seven of 67 participants (70.1%) had SCOs. Patients with PHP1A and PPHP had similar prevalences and degrees of ossification formation. Patients with frameshift and nonsense mutations had much more extensive SCOs than those with missense mutations. Males were affected more than females. There was no correlation with hormonal status or BMI.
There is a similar prevalence of SCOs in PHP1A and PPHP, and the extent of SCO formation correlates with the severity of the mutation. Males are affected more extensively than females, and the SCOs tend to worsen with age.
阿利布莱特遗传性骨营养不良症（AHO）是由 GNAS 杂合失活突变引起的。根据突变等位基因的亲本来源，患者会发展为假性甲状旁腺功能减退症 1A 型（PHP1A），表现为多激素抵抗和严重肥胖，或假性假性甲状旁腺功能减退症（PPHP），没有激素异常或明显肥胖。皮下骨化（SCO）是 PHP1A 和 PPHP 两种疾病患者存在大量发病率的原因。
本研究旨在调查 PHP1A 与 PPHP 患者中 SCO 形成的先前未确定的患病率，以及与基因型、性别、年龄、激素抵抗和体重指数（BMI）的可能相关性。
本研究通过一位经验丰富的医生在 16 年内进行的体格检查，对患有 AHO 的患者进行 SCO 评估。
肯尼迪克里格研究所的阿利布莱特诊所；约翰霍普金斯医院的临床与转化研究研究所；康涅狄格儿童医疗中心的阿利布莱特中心。
我们评估了 67 名患有 AHO（49 名患有 PHP1A，18 名患有 PPHP）的患者，他们均有 GNAS 基因突变的记录。
SCO 与基因型、性别、年龄、激素抵抗和 BMI 的关系。
67 名参与者中有 47 名（70.1%）存在 SCO。PHP1A 和 PPHP 患者的患病率和骨化程度相似。框移和无义突变的患者的 SCO 比错义突变的患者更广泛。男性比女性更容易受到影响。与激素状态或 BMI 没有相关性。
PHP1A 和 PPHP 中 SCO 的患病率相似，SCO 形成的程度与突变的严重程度相关。男性比女性受影响更广泛，SCO 随着年龄的增长而恶化。
