IDIOPATHIC INFANTILE HYPERCALCEMIA â€“ CASE REPORT

Snezana Palchevska; Simonida Spasevska; Jana Jovanovska; Velibor Tasic; Natasha Aluloska

Snezana Palchevska Neonatology and Neonatal intensive care unit, Clinical hospital Adzibadem Sistina, Skopje, R. of North Macedonia
Simonida Spasevska Neonatology and Neonatal intensive care unit, Clinical hospital Adzibadem Sistina, Skopje, R. of North Macedonia
Jana Jovanovska Neonatology Department, University Children`s hospital, Medical Faculty, Ss Cyril and Methodius University, Skopje, R.of North Macedonia
Velibor Tasic Nephrology Department, University Children`s hospital, , Medical Faculty, Ss Cyril and Methodius University, Skopje, R.of North Macedonia
Natasha Aluloska Neonatology Department, University Children`s hospital, Medical Faculty, Ss Cyril and Methodius University, Skopje, R.of North Macedonia

Abstract

Idiopathic Infantile Hypercalcemia (IIH) is a rare genetic disease which cardinal features is failure to thrive, polyuria, dehydration, vomiting, seizures, lethargy, comma and if unrecognized and untreated may result in death. Laboratory investigations show hypercalcemia, hypercalciuria, elevated values of 1, 25 (OH) D3 and suppressed levels of parathormon. Ultrasound study usually reveals bilateral medullary echogenicity typical for nephrocalcinosis. Emergency treatment consists from large hydration, prednisolone, calcitonin and biphosphonates, which were used with success. In this report we present a 6 month old female infant who came to our attention due to growth delay as a consequence of polyuria, vomiting and poor apetite.Dietary management with withdrawal of vitamin D and reduction of calcium intake significantly improved the general health status and normalized the serum biochemistry. The diagnosis was established with mutational analysis of the CYP24A1 gene.

Key words: idiopathic infantile hypercalcemia, CYP24A1, vitamin D, nephrocalcinosis.

https://doi.org/10.55302/JMS2141029p

References

1.Fencl F, BlÃ¡hovÃ¡ K, Schlingmann KP, Konrad M, Seeman T.Severe hypercalcemic crisis in an infant with idiopathic infantile hypercalcemia caused by mutation in CYP24A1 gene. Eur J Pediatr. 2013; 172:45-9
2.Zajadacz B, Juszkiewicz A. Nephrocalcinosis in a 2-month-old girl suffering from a mild variant of idiopathic infantile hypercalcemia. Wiad Lek. 2004;57:710-2.
3.Pronicka E, RowiÅ„ska E, Kulczycka H, Lukaszkiewicz J, Lorenc R, Janas R. Persistent hypercalciuria and elevated 25-hydroxyvitamin D3 in children with infantile hypercalcaemia. Pediatr Nephrol. 1997; 11:2-6.
4.Gut J, KutÃlek Å . Idiopathic infantile hypercalcaemia in 5-month old girl. Prague Med Rep. 2011; 112:124-31
5.Dinour D, Beckerman P, Ganon L, Tordjman K, Eisenstein Z, Holtzman EJ. Loss-of-function mutations of CYP24A1, the vitamin D 24-hydroxylase gene, cause long-standing hypercalciuric nephrolithiasis and nephrocalcinosis. J Urol. 2013; 190:552-7.
6. Kenny J, Lees MM, Drury S, Barnicoat A, Van't Hoff W, Palmer R, Morrogh D, Waters JJ, Lench NJ, Bockenhauer D. Sotos syndrome, infantile hypercalcemia, and nephrocalcinosis: a contiguous gene syndrome. Pediatr Nephrol. 2011; 26:1331-4
7.Udwin O. A survey of adults with Williams syndrome and idiopathic infantile hypercalcaemia. Dev Med Child Neurol. 1990; 32:129-41.
8.Euteneuer J, Carvalho CM, Kulkarni S, Vineyard M, Grady RM, Lupski JR, Shinawi M.Molecular and phenotypic characterization of atypical Williams-Beuren syndrome. Clin Genet. 2014; 86:487-91
9.Leme DE, Souza DH, Mercado G, Pastene E, Dias A, Moretti-Ferreira D.Assessment of clinical scoring systems for the diagnosis of Williams-Beuren syndrome. Genet Mol Res. 2013; 12:3407-11.
10.Schlingmann KP, Kaufmann M, Weber S et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011; 365:410-21.
11.Dauber A, Nguyen TT, Sochett E, Cole DE, Horst R, Abrams SA, Carpenter TO, Hirschhorn JN. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia. J Clin Endocrinol Metab. 2012; 97:E268-74.
12.Jones G, Prosser DE, Kaufmann M. 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D. Arch Biochem Biophys. 2012; 523:9-18.
13.Mizusawa Y, Burke JR. Prednisolone and cellulose phosphate treatment in idiopathic infantile hypercalcaemia with nephrocalcinosis. J Paediatr Child Health. 1996; 32:350-2.
14. Shimizu H, Kodama S, Takeuchi A, Matui T, Nakao H, Sakurai T, Kobayashi T. Idiopathic infantile hypercalcemia discovered in the newborn period. Acta Paediatr Jpn. 1994; 36:720-3.
15.Alon U, Berkowitz D, Berant M. Idiopathic infantile hypercalcemia: rapid response to treatment with calcitonin. Child Nephrol Urol. 1992;12:47-50.
16.Meusburger E, MÃ¼ndlein A, Zitt E, Obermayer-Pietsch B, Kotzot D, Lhotta K. Medullary nephrocalcinosis in an adult patient with idiopathic infantile hypercalcaemia and a novel CYP24A1 mutation. Clin Kidney J. 2013; 6:211-215.
17.Dinour D, Davidovits M, Aviner S, Ganon L, Michael L, Modan-Moses D, Vered I, Bibi H, Frishberg Y, Holtzman EJ. Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake. Pediatr Nephrol. 2015; 30:145-52.
18.Castanet M, Mallet E, Kottler ML. Lightwood syndrome revisited with a novel mutation in CYP24 and vitamin D supplement recommendations. J Pediatr. 2013; 163:1208-10.
19.Janiec A, Halat-Wolska P, Obrycki Å, Ciara E, WÃ³jcik M, PÅ‚udowski P, Wierzbicka A, Kowalska E, KsiÄ…Å¼yk JB, KuÅ‚aga Z, Pronicka E, Litwin M. Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations. Nephrol Dial Transplant. 2020 Oct 25:gfaa178. doi: 10.1093/ndt/gfaa178. Online ahead of print.
20.Streeten EA, Zarbalian K, Damcott CM. CYP24A1 mutations in idiopathic infantile hypercalcemia. N Engl J Med. 2011; 365:1741-2;
21.Wolf P, MÃ¼ller-Sacherer T, Baumgartner-Parzer S, Winhofer Y, Kroo J, Gessl A, Luger A, Krebs M. A Case of "Late-Onset" Idiopathic Infantile Hypercalcemia Secondary to Mutations in the CYP24A1 Gene. Endocr Pract. 2014; 20:e91-5.