Abstract
Background
Four genes responsible for pseudohypoaldosteronism type II (PHA-II) have been identified, thereby facilitating molecular diagnostic testing.
Case-Diagnosis/Treatment
A 1-year-old boy with prolonged hyperkalemia, metabolic acidosis, hyperchloremia, growth delay, and mild hypertension was diagnosed with PHA-II based on the detection of exon 9 skipping in CUL3 mRNA. The impaired splicing was the result of a de novo, previously unreported single nucleotide substitution in the splice acceptor site of CUL3 intron 8. Among the four genes reported to be involved in PHA-II, CUL3 was the primary suspect in our patient because in patients with the CUL3 mutation, the onset of disease is often early in infancy and the phenotypes of PHA-II are more severe. Our patient was treated with trichlormethiazide, which inhibits the function of the sodium-chloride co-transporter (NCC), and the outcome was favorable, with correction of body fluids and blood electrolyte homeostasis.
Conclusion
Since chronic acidosis and hypertension associated with PHA-II can result in delayed growth and development in pediatric patients, genetic analysis to detect the CUL3 mutation and to enable intervention early in the disease course would be beneficial for infants with suspected PHA-II.
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Abbreviations
- CRL complex:
-
Cullin-ring E3 ubiquitin ligase complex
- NCC:
-
Sodium-chloride co-transporter
- PHA-II:
-
Pseudohypoaldosteronism; hyperkalemia type II
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Acknowledgments
We thank Hideaki Amaki, and Tamaki Kato for the excellent technical assistance. This work was supported by the Ministry of Education, Science, and Culture of Japan (Grant-in-Aid 20591263; H.K.), by the Health and Labour Sciences Research Grant of Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan (N.S., H.K.), by Kawano Masanori Memorial Foundation for Promotion of Pediatrics (No. 23–03; H.K.).
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Osawa, M., Ogura, Y., Isobe, K. et al. CUL3 gene analysis enables early intervention for pediatric pseudohypoaldosteronism type II in infancy. Pediatr Nephrol 28, 1881–1884 (2013). https://doi.org/10.1007/s00467-013-2496-6
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DOI: https://doi.org/10.1007/s00467-013-2496-6