1例Ⅰb型假性甲状旁腺功能减退症合并低钾血症的临床和遗传特征分析

Clinical and genetic analysis of a case of type Ib pseudohypoparathyroidism complicated with hypokalemia

回顾性分析了1例Ⅰb型假性甲状旁腺功能减退症(pseudohypoparathyroidism,PHP)合并低钾血症的年轻女性患者,反复发作肢体无力伴双上肢搐搦,实验室检查示低血钙、高血磷、高甲状旁腺激素、低尿钙及低血钾;基因检测未发现鸟嘌呤核苷酸结合蛋白α刺激性活性肽(GNAS)及突触融合蛋白16(STX16)基因突变,存在溶质载体家族4成员A1(SLC4A1)基因母源性杂合突变,多重连接酶依赖性探针扩增检测(multiplex ligation-dependent probe amplification,MLPA)提示GNAS反义转录本(GNAS-AS)、非编码外显子(GNAS-A/B)、超大片段(extra-large Gsαvariant,GNAS-XLsα)甲基化缺失,神经内分泌蛋白55(neuroendocrine secretory protein 55,NESP55)过度甲基化。通过分析该患者诊疗经过并复习相关文献,帮助提高对Ⅰb型PHP的认识和诊治,对合并低钾血症的原因进行解释。

A young female patient with typeⅠb pseudohypoparathyroidism(PHP)complicated with hypokalemia was retrospectively analyzed.She experienced recurrent episodes of limb weakness with bilateral upper limb spasms.Laboratory tests revealed low blood calcium,high blood phosphate,elevated parathyroid hormone,low urine calcium,and hypokalemia.Genetic testing did not detect mutations in guanine nucleotide-binding proteinα-stimulating activity polypeptide(GNAS)or syntaxin 16(STX16)genes,but identified a maternal heterozygous mutation in solute carrier family 4 member A1(SLC4A1)gene.Multiple ligation-dependent probe amplification(MLPA)indicated GNAS antisense transcript(GNAS-AS),non-coding exons(GNAS-A/B),extra-large Gsαvariant(GNAS-XLα)methylation loss,and neuroendocrine secretory protein 55(NESP55)hypermethylation.Through analysis of her diagnosis and treatment process and review of relevant literature,we aim to enhance understanding and management of type Ib PHP.