ESPN 51th Annual Meeting

ESPN 2018


 
RARE CAUSE OF NEPHROCALCINOSIS DUE TO MUTATIONS IN THE CYP24A1 GENE
MARINA SHUMIKHINA 1 OLGA CHUGUNOVA 2 ANZHELIKA GUREVITCH 1 IGOR CHUGUNOV 3 ANATOLIY TYULPAKOV 3

1- FILATOV CHILDREN’S CLINICAL HOSPITAL №13, MOSCOW, RUSSIA
2- PIROGOV RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY, MOSCOW, RUSSIA
3- ENDOCRINOLOGY RESEARCH CENTER, MINISTRY OF HEALTHCARE OF THE RUSSIA, MOSCOW, RUSSIA
 
Introduction:

 Loss-of-function mutations of CYP24A1, which encodes the enzyme 1,25-dihydroxyvitamin D - 24-hydroxylase, is characterized by increased sensitivity to vitamin D, leading to infantile hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis.

Material and methods:

We present two clinical cases of children from different families with medullary nephrocalcinosis due to mutations in the CYP24A1 gene.

Results:

Case 1: A 9-month-old boy presented with unfebrile urinary tract infection, without congenital anomalies of urinary tract, but with medullary nephrocalcinosis on ultrasound examination. In laboratory tests: hypercalciuria (Ca/Cr – 1.1 mg/mg (N<0,8), highly elevated serum calcium concentration (3.56 mmol/L), and normal level of 25-hydroxyvitamin D (68 pg/mL) in combination with suppressed levels of circulating parathormone (less than 3 pg/mL). Unfortunately, it was not possible to determine the level of 1.25 dihydroxyvitamin D for technical reasons. Considering to hypercalcemia, unusual phenotype, a genetic analysis on Williams syndrome was performed at 1 y.o., but deletions/duplications of genes in locus 7q11.23 was not detected. The combination of persist hypercalciuria (Ca/Cr – 0.9 mg/mg (N<0.53), hypercalcemia (2.95 mmol/L) with hypoparathyroidism (less than 3 pg/mL) and medullary nephrocalcinosis allowed to suspect idiopathic infantile hypercalcemia and hypercalciuric nephrocalcinosis. Genetic analysis at 2 y.o. revealed a compound heterozygous mutation in CYP24A1. Case 2: A 7-year-old girl presented with repetitive signs of medullary nephrocalcinosis (her early medical history was unremarkable), hypercalciuria (Ca/Cr – 0,27 mg/mg (N<0,21), slightly elevated serum calcium concentration (2.6 mmol/L), and normal level of 25-hydroxyvitamin D (55.5 pg/mL) in combination with suppressed levels of circulating parathormone (less than 3 pg/mL). Genetic analysis revealed a compound heterozygous mutation in CYP24A1. 

Conclusions:

 CYP24A1 mutations are a rare cause of hypercalciuria and respectively, of medullary nephrocalcinosis and nephrolithiasis, that can lead to chronic kidney disease. Early detection of genetic basis of medullary nephrocalcinosis offers an opportunity to develop treatment options and management of kidney functional decline.