Clinical features and genetic results of 6 cases with pseudohypoaldosteronism type 1 and literature review / 中华实用儿科临床杂志

Objective:To summarize clinical features, diagnosis, treatment, and follow-up of children with pseudohypoaldosteronism type 1 (PHA1) and review relevant literatures to improve the understanding of the disease and reduce misdiagnosis.Methods:Six children with the main performance of salt losing treated in the Shanghai Children′s Hospital from January 2015 to December 2018, who were diagnosed as PHA1 after relevant auxiliary examinations and genetic tests.They were classified and analyzed for their treatment courses and follow-up prognosis.Results:Six children with PHA1 had varying degrees of salt losing, dehydration and infection.After the examination, 3 cases with urinary system malformations were diagnosed as secondary PHA1.Genetic testing of 2 cases revealed 2 hete-rozygous mutations c. 1439+ 1G>C and c. 875+ 1G>A in the intron region of the SCNN1A gene, and they were diagnosed as multiple target organ defect/systemic PHA1 according to American College of Medical Genetics and Genomics(ACMG) guidelines.The other case failed to be examined by genetic testing due to the refusal of parents, and was finally diagnosed as renal PHA1 according to clinical diagnosis and treatment.Conclusions:PHA1 is a rare cause of infant salt-losing syndrome, renal and secondary PHA1 children can recover quickly after sodium supplementation and the secondary factors are removed; while multiple target organ defect/systemic PHA1 has severe clinical manifestations, electrolyte imbalance is not easy to correct, and fatal arrhythmia is prone to occur, the mortality rate is high.It is easy to be misdiagnosed in clinical practice.Auxiliary examination and genetic testing can help to diagnose and classify PHA1, as well as individualized treatment.

Pseudo hypoaldosteronism type 1B due to novel deletion mutation in SCNN1A gene

Pseudo hypoaldosteronism type 1B (PHA1B) is a systemic form of salt wasting. Children present after the first week of life with typical symptoms of an adrenal crisis. PHA1B is caused by autosomal recessive homozygous mutations in genes encoding epithelial sodium channels (ENaC) subunits ?, ? and ?. ENaC are widespread and present in renal tubules, airways, colon, sweat and salivary glands. Electrolyte imbalance is significant with severe hyponatremia, hyperkalemia and metabolic acidosis. In early life until approximately one year of age electrolytes remain unstable despite active management but then gradually improve. The mainstay of treatment is high dose salt replacement, sodium bicarbonate and sodium polystyrene therapy. The adequate treatment and monitoring can result in normal physical and psychomotor development. We present a case of PHA1B with severe intractable electrolyte imbalances in neonatal period. The genetic sequence revealed a novel homozygous deletion mutation in exon 4 of the SCNN1A gene (c.942delC, p.N315Tfs*16).