A Case Report of Compound Heterozygous CYP24A1 Mutations Leading to Nephrolithiasis Successfully Treated with Ketoconazole

Peiris, Emma; Wusirika, Raghav

doi:10.1159/000485243

Cited by 9 publications

(2 citation statements)

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“…[ 30 ] reported a 2-year-old patient with a history of symptomatic IH and nephrocalcinosis in infancy who, at the age of 2 years, had reduced GFR (74 mL/min/1.73 m 2 ), but in whom nephrocalcinosis disappeared. It should be noted that genetic variants of CYP24A1 or SLC34A1 were found in adults who were diagnosed due to recurrent nephrolithiasis, with or without nephrocalcinosis [ 12 , 20 , 32 , 34–42 ]. The hypothesis of CYP24A1 mutations as a cause of nephrocalcinosis or nephrolithiasis is also supported by the report of Molin et al .…”

Section: Discussionmentioning

confidence: 99%

Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations

Janiec

Halat-Wolska

Obrycki

et al. 2020

Nephrology Dialysis Transplantation

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Background Infantile hypercalcaemia (IH) is a vitamin D3 metabolism disorder. The molecular basis for IH is biallelic mutations in the CYP24A1 or SLC34A1 gene. These changes lead to catabolism disorders (CYP24A1 mutations) or excessive generation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (SLC34A1 mutations). The incidence rate of IH in children and the risk level for developing end-stage renal disease (ESRD) are still unknown. The aim of this study was to analyse the long-term outcome of adolescents and young adults who suffered from IH in infancy. Design Forty-two children (23 girls; average age 10.7 ± 6.3 years) and 26 adults (14 women; average age 24.2 ± 4.4 years) with a personal history of hypercalcaemia with elevated 1,25(OH)2D3 levels were included in the analysis. In all patients, a genetic analysis of possible IH mutations was conducted, as well as laboratory tests and renal ultrasonography. Results IH was confirmed in 20 studied patients (10 females). CYP24A1 mutations were found in 16 patients (8 females) and SLC34A1 in 4 patients (2 females). The long-term outcome was assessed in 18 patients with an average age of 23.8 years (age range 2–34). The average glomerular filtration rate (GFR) was 72 mL/min/1.73 m2 (range 15–105). Two patients with a CYP24A1 mutation developed ESRD and underwent renal transplantation. A GFR <90 mL/min/1.73 m2 was found in 14 patients (77%), whereas a GFR <60 mL/min/1.73 m2 was seen in 5 patients (28%), including 2 adults after renal transplantation. Three of 18 patients still had serum calcium levels >2.6 mmol/L. A renal ultrasound revealed nephrocalcinosis in 16 of 18 (88%) patients, however, mild hypercalciuria was detected in only one subject. Conclusions Subjects who suffered from IH have a greater risk of progressive chronic kidney disease and nephrocalcinosis. This indicates that all survivors of IH should be closely monitored, with early implementation of preventive measures, e.g. inhibition of active metabolites of vitamin D3 synthesis.

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Section: Discussionmentioning

confidence: 99%

Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations

Janiec

Halat-Wolska

Obrycki

et al. 2020

Nephrology Dialysis Transplantation

View full text Add to dashboard Cite

show abstract

“…Infantile hypercalcemia type 1 is caused by biallelic mutations in CYP24A1 , which have also been reported in families with severe hypercalcemia following vitamin D supplementation and in adults with hypercalcemia and hypercalciuria [ 24 ]. The inhibition of vitamin D synthesis with fluconazole or ketoconazole has been shown to be effective in patients with hypercalcemia and nephrolithiasis [ 92 ].…”

Section: Monogenic Disordersmentioning

confidence: 99%