CUL3 gene analysis enables early intervention for pediatric pseudohypoaldosteronism type II in infancy

• Published in: Pediatric nephrology (Berlin, West) West), 2013-09, Vol.28 (9), p.1881-1884
• Main Authors: Osawa, Madori, Ogura, Yumi, Isobe, Kiyoshi, Uchida, Shinichi, Nonoyama, Shigeaki, Kawaguchi, Hiroyuki
• Format: Article
• Language: English
• Subjects: Acid-Base Imbalance - blood; Acid-Base Imbalance - genetics; Acidosis; Acidosis - etiology; Acidosis - therapy; Bicarbonates - blood; Blood pressure; Blood Pressure - physiology; Brief Report; Case studies; Children; Chloride; Chlorides - blood; Cullin Proteins - genetics; Diagnostic tests; Diseases; Diuretics - therapeutic use; Early intervention; Exons - genetics; Genes; Genetic Testing; Humans; Hyperkalemia; Hypertension; Hypoaldosteronism; Infant; Introns - genetics; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolism; Mutation; Nephrology; Patients; Pediatrics; Potassium; Potassium - blood; Pseudohypoaldosteronism - diagnosis; Pseudohypoaldosteronism - genetics; Pseudohypoaldosteronism - therapy; Real-Time Polymerase Chain Reaction; RNA, Messenger - genetics; Sodium; Trichlormethiazide - therapeutic use; Urology
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-013-2496-6

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.