Cancer Genetics, Kolling Institute of Medical Research, Sydney, North South Wales, Australia.
Department of Genetics, Royal North Shore Hospital, Sydney, Australia.
J Clin Endocrinol Metab. 2020 Jul 1;105(7). doi: 10.1210/clinem/dgaa279.
Familial hypoparathyroidism has a heterogeneous presentation where patients usually have low parathyroid hormone (PTH) levels due to impaired production or secretion. This contrasts with pseudohypoparathyroidism, in which PTH resistance is usually associated with an elevated serum PTH. High levels of circulating PTH can also be due to bioinactive PTH, which is difficult to distinguish from pseudohypoparathyroidism on biochemical grounds.
We report on 2 sisters from consanguineous parents who presented with tetany at birth and were diagnosed with congenital hypocalcemia. Serum PTH levels were normal for many years, but progressively increased in midadulthood to greater than 100x the upper limit of normal on multiple assays. Homozygosity mapping was performed on 1 sister that demonstrated loss of heterozygosity (LOH) around PTH. Sequencing revealed a previously unreported variant, c.94T>C, predicting a codon change of p.Ser32Pro that is biologically inactive.
This case report shows a previously unreported unusual biochemical phenotype of a rising PTH in the context of a novel PTH mutation. This expands the evolving genotypes associated with hypoparathyroidism without established gene mutations.
家族性甲状旁腺功能减退症的表现具有异质性，患者通常由于甲状旁腺激素 (PTH) 的产生或分泌受损而导致 PTH 水平降低。这与假性甲状旁腺功能减退症形成对比，假性甲状旁腺功能减退症中 PTH 抵抗通常与血清 PTH 升高有关。循环 PTH 水平升高也可能是由于生物活性 PTH，由于生化原因，很难将其与假性甲状旁腺功能减退症区分开来。
我们报告了 2 例来自近亲的姐妹，她们在出生时出现抽搐，并被诊断为先天性低钙血症。多年来，血清 PTH 水平一直正常，但在成年中期逐渐升高，多次检测超过正常上限 100 倍。对 1 位姐妹进行了同源性作图，显示 PTH 周围的杂合性丢失 (LOH)。测序显示了一个以前未报道的变异，c.94T>C，预测了生物活性降低的 p.Ser32Pro 密码子改变。
本病例报告显示了一种以前未报道的不常见的生化表型，即在新型 PTH 突变的情况下，PTH 逐渐升高。这扩展了与未确定基因突变相关的不断发展的甲状旁腺功能减退症基因型。
