Clinical and genetic analysis of pseudohypoparathyroidism complicated by hypokalemia: a case report and review of the literature

Abstract

Background Pseudohypoparathyroidism (PHP) encompasses a highly heterogenous group of disorders, characterized by parathyroid hormone (PTH) resistance caused by mutations in the GNAS gene or other upstream targets. Here, we investigate the characteristics of a female patient diagnosed with PHP complicated with hypokalemia, and her family members. Case presentation and gene analysis A 27-year-old female patient occasionally exhibited asymptomatic hypocalcemia and hypokalemia during her pregnancy 1 year ago. Seven months after delivery, she experienced tetany and dysphonia with diarrhea. Tetany symptoms were relieved after intravenous calcium gluconate supplementation and she was then transferred to our Hospital. Laboratory assessments of the patient revealed hypokalemia, hypocalcemia and hyperphosphatemia despite elevated PTH levels. CT scanning of the brain revealed globus pallidus calcification. Possible mutations in GNAS and hypokalemia related genes were identified using WES, exon copies of STX16 were analized by MLPA and the methylation status of GNAS in three differential methylated regions (DMRs) was analyzed by methylation-specific polymerase chain reaction, followed by confirmation with gene sequencing. The patient was clinically diagnosed with PHP-1b. Loss of methylation in the A/B region and hypermethylation in the NESP55 region were detected. No other mutations in GNAS or hypokalemia related genes and no deletions of STX16 exons were detected. A negative family history and abnormal DMRs in GNAS led to a diagnosis of sporadic PHP-1b of the patient. Conclusions Hypokalemia is a rare disorder associated with PHP-1b. Analysis of genetic and epigenetic mutations can aid in the diagnosis and accurate subtyping of PHP.

A Case of Pseudohypoparathyroidism Misdiagnosed as Idiopathic Epilepsy for 5 Years: Clinical Analysis and Follow-up Outcomes

“…In the present patient, the genetic analysis revealed methylation defects in the GNAS gene in the form of LOMs in the DMRs of GNAS-AS1 , GNAS-XL , and GNAS-A/B and a GOM in the DMR of the GNAS-NESP55 region. 12 On physical examination, she did not exhibit any signs of AHO, and there were no signs of other types of hormone resistance other than PTH resistance. These findings were consistent with the diagnosis of PHPIb.…”

Interpreting epigenetic causes of recurrent hypokalemia and seizures: Gitelman syndrome co‐exist with pseudohypoparathyroidism type 1B

“…However, no pathogenic mutations in genes related to Bartter or GS were found. 17,18 Interestingly, potassium levels were reported to revert to normal after calcitriol and calcium supplementation, implying that the hypokalemia was related to PHP. 17…”