Gopal-Kothandapani Jaya Sujatha, Doshi Arpan B, Smith Kath, Christian Martin, Mushtaq Talat, Banerjee I, Padidela Raja, Ramakrishnan Renuka, Owen Catherine, Cheetham Timothy, Dimitri Paul
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
Sheffield Medical School, University of Sheffield, Sheffield, UK.
J Pediatr Endocrinol Metab. 2019 Sep 25;32(9):959-967. doi: 10.1515/jpem-2018-0538.
Background Type I pseudohypoaldosteronism (PHA1) is a rare condition characterised by profound salt wasting, hyperkalaemia and metabolic acidosis due to renal tubular resistance to aldosterone (PHA1a) or defective sodium epithelial channels (PHA1b or systemic PHA). Our aim was to review the clinical presentation related to the genotype in patients with PHA1. Methods A questionnaire-based cross-sectional survey was undertaken through the British Society of Paediatric Endocrinology and Diabetes (BSPED) examining the clinical presentation and management of patients with genetically confirmed PHA1. We also reviewed previously reported patients where genotypic and phenotypic information were reported. Results Genetic confirmation was made in 12 patients with PHA1; four had PHA1a, including one novel mutation in NR3C2; eight had PHA1b, including three with novel mutations in SCNN1A and one novel mutation in SCNN1B. It was impossible to differentiate between types of PHA1 from early clinical presentation or the biochemical and hormonal profile. Patients presenting with missense mutations of SCNN1A and SCNN1B had a less marked rise in serum aldosterone suggesting preservation in sodium epithelial channel function. Conclusions We advocate early genetic testing in patients with presumed PHA1, given the challenges in differentiating between patients with PHA1a and PHA1b. Clinical course differs between patients with NR3C2 and SCNN1A mutations with a poorer prognosis in those with multisystem PHA. There were no obvious genotype-phenotype correlations between mutations on the same gene in our cohort and others, although a lower serum aldosterone may suggest a missense mutation in SCNN1 in patients with PHA1b.
背景 Ⅰ型假性醛固酮增多症（PHA1）是一种罕见疾病，其特征为由于肾小管对醛固酮抵抗（PHA1a）或钠上皮通道缺陷（PHA1b或全身性PHA）导致严重的盐消耗、高钾血症和代谢性酸中毒。我们的目的是回顾PHA1患者中与基因型相关的临床表现。方法 通过英国儿科学内分泌与糖尿病学会（BSPED）进行了一项基于问卷的横断面调查，研究基因确诊的PHA1患者的临床表现和管理。我们还回顾了先前报道的有基因型和表型信息的患者。结果 12例患者基因确诊为PHA1；4例为PHA1a，包括NR3C2中的1个新突变；8例为PHA1b，包括SCNN1A中的3个新突变和SCNN1B中的1个新突变。无法从早期临床表现或生化及激素特征区分PHA1的类型。出现SCNN1A和SCNN1B错义突变的患者血清醛固酮升高不明显，提示钠上皮通道功能保留。结论 鉴于区分PHA1a和PHA1b患者存在挑战，我们主张对疑似PHA1的患者进行早期基因检测。NR3C2和SCNN1A突变患者的临床病程不同，多系统PHA患者预后较差。在我们的队列和其他研究中，同一基因上的突变之间没有明显的基因型-表型相关性，尽管血清醛固酮较低可能提示PHA1b患者SCNN1存在错义突变。
