Naslov
Nefrokalcinoza, hipomagnezemija i hiperkalciurija u brata i sestre: jesu li geni sudbina?
(Nephrocalcinosis, hypomagnesemia and hypercalciuria in brother and sister: are genes destiny?)

Autori
Jakopčić, Ivan ; Matković, Hana ; Kos, Ivanka ; Lamot, Lovro ; Vrljičak, Kristina

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Archives of Diseases in Childhood / - , 2021, A161-A161

Skup
14th Congress of Croatian Pediatric Society

Mjesto i datum
Zagreb, Hrvatska, 07.10.2021. - 09.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Nephrocalcinosis, hypomagnesemia and hypercalciuria in brother and sister: are genes destiny?
(nephrocalcinosis ; hypomagnesemia ; hypercalciuria ; pediatrics ; genetics)

Sažetak
Introduction Nephrocalcinosis is a condition characterized by calcium deposition in the renal parenchyma that can lead to a renal failure. Typically, it is not accompanied by specific symptoms, but lesser number of children might develop a recurrent urinary tract infection (rUTI). Therefore, in children with rUTI nephrocalcinosis should be considered as a possible underlying cause, prompting additional imaging and laboratory diagnostics, and depending on the findings, in some cases even genetic testing. Case Report We report the case of an eleven-year- old girl and her seven-year-old brother with nephrocalcinosis. The girl initially presented at the age of four with recurrent urinary tract infections and bilateral nephrocalcinosis detected by renal ultrasound. During the further evaluation hypercalciuria, hypomagnesaemia, hypermagnesiuria, hyperparathyroidism, hyperuricemia, decreased glomerular filtration and bilateral optic neuropathy were detected. Since hereditary disease was suspected, her younger brother underwent a renal ultrasound at the age of 4 months with the similar finding of bilateral nephrocalcinosis. Moreover, laboratory testing indicated the presence of same abnormalities as in his sister, but in the absence of other clinical symptoms. Finally, targeted gene sequencing in both siblings (Blueprint Nephrolitiasis panel with 35 genes) identified in CLDN16 gene a novel heterozygous frameshift variant c.332_333del, p. (Thr111Lysfs*15) previously not described, as well as heterozygous missense variant c.358T>C, p. (Cys120Arg) previously described in one person. Both variants are classified by in silico methods as pathogenic, while sequencing data strongly suggests that they are on different parenteral alleles (in trans position). Discussion Pathogenic variants of the CLDN16 gene cause renal hypomagnesaemia, an autosomal recessive tubulopathy also known as familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC). This disease is characterized by excessive loss of magnesium and calcium in the urine, polyuria, polydipsia, bilateral nephrocalcinosis and progressive chronic renal failure. It can also affect the eye and present with symptoms such as strabismus, nystagmus, hyperopia, myopia and astigmatism. Biochemical findings characteristic of the disease include hyperuricemia, hypermagnesiuria, hypercalciuria, hypocitraturia, hematuria and leukocyturia, often without bacteriuria. The onset of the disease is usually in the childhood or adolescence. Magnesium citrate as a replacement therapy in combination with thiazide diuretics is most commonly used for treatment, although in the advanced stage of the disease kidney transplantation remains the only viable option. In the presented case of siblings, despite the same complex heterozygous variants previously undescribed in the literature, there are marked differences in clinical phenotype, demonstrating a significant role of other, external factors in the development of the disease. Nevertheless, in all patients with nephrocalcinosis, it is important to consider genetic testing in order to confirm underlying monogenic diseases, determine the risk in other family members, select the most appropriate treatment options and predict the possible course.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA