Itoh Masatsune, Okajima Michiko, Kittaka Yuko, Yachie Akihiro, Wada Taizo, Saikawa Yutaka
Department of Pediatrics, Kanazawa Medical University, Kanazawa, Japan.
Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Kanazawa, Japan.
Bone Rep. 2022 Apr 14;16:101569. doi: 10.1016/j.bonr.2022.101569. eCollection 2022 Jun.
Pseudohypoparathyroidism type 1a (PHP1a) is a genetic disorder caused by heterozygous loss-of-function mutations on the maternal allele of the gene. Patients with PHP1a predominantly exhibit parathyroid hormone (PTH) resistance and physical features of Albright's hereditary osteodystrophy. We report two unrelated cases with PHP1a who developed tertiary hyperparathyroidism (HPT). Molecular analyses of the gene identified a previously known heterozygous 4-bp deletion (c. 565_568delGACT) in exon 7 in case 1 and a novel heterozygous missense mutation (p.Lys233Glu) in exon 9 in case 2. Both patients developed tertiary HPT associated with hyperfunctioning parathyroid glands during long-term treatment of hypocalcemia. Case 1 had severe osteoporosis and underwent parathyroidectomy. Case 2 was asymptomatic with no evidence of bone diseases associated with tertiary HPT. PHP1a patients are at risk of developing tertiary HPT and should be treated with sufficient doses of calcium and vitamin D to achieve serum PTH levels within the mid - normal to double the upper limit of the normal range, regardless of serum calcium levels.
1a型假性甲状旁腺功能减退症（PHP1a）是一种由该基因母本等位基因杂合功能丧失突变引起的遗传性疾病。PHP1a患者主要表现为甲状旁腺激素（PTH）抵抗以及Albright遗传性骨营养不良的身体特征。我们报告了两例患PHP1a且发生了三发性甲状旁腺功能亢进症（HPT）的无血缘关系病例。对该基因的分子分析在病例1的第7外显子中鉴定出一个先前已知的4碱基缺失（c.565_568delGACT），在病例2的第9外显子中鉴定出一个新的杂合错义突变（p.Lys233Glu）。两名患者在长期低钙血症治疗期间均发生了与甲状旁腺功能亢进相关的三发性HPT。病例1患有严重骨质疏松症并接受了甲状旁腺切除术。病例2无症状，没有与三发性HPT相关的骨病证据。PHP1a患者有发生三发性HPT的风险，无论血清钙水平如何，均应以足够剂量的钙和维生素D进行治疗，以使血清PTH水平达到正常范围上限的中值至两倍。
