Successful treatment of hypercalcaemia associated with a<i>CYP24A1</i>mutation with fluconazole: Fig. 1.

Sayers, Judith A.; Hynes, Ann Marie; Srivastava, Shalabh; Dowen, Frances; Quinton, Richard; Datta, Harish K.; Sayer, John A.

doi:10.1093/ckj/sfv028

Cited by 84 publications

(47 citation statements)

References 9 publications

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“…The ratio of 25(OH)D 3 to 24,25(OH) 2 D 3 (or its reciprocal) has been proposed as an indicator of 24-hydroxylase deficiency and response to vitamin D supplementation [19]. Loss-of-function mutations in CYP24A1, the gene that encodes 24-hydroxylase, result in a range of clinical disorders, among them idiopathic infantile hypercalcaemia (IIH) and adult-onset nephrocalcinosis and nephrolithiasis [20]. Because serum 24(OH)D 3 is low not only in 24-hydroxylase deficiency but also in vitamin D deficiency, the ratio of calcidiol to its catabolite may indicate enzymatic deficiency: normal range of the ratio rarely exceeds 20, whereas in IIH it is greater than 80 [19].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D status including 3-epi-25(OH)D3 among adult patients with thyroid disorders during summer months

Kmieć

Minkiewicz

Rola³

et al. 2018

Endokrynologia Polska

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Section: Discussionmentioning

confidence: 99%

Vitamin D status including 3-epi-25(OH)D3 among adult patients with thyroid disorders during summer months

Kmieć

Minkiewicz

Rola³

et al. 2018

Endokrynologia Polska

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“…Pending further study to establish the most effective long-term therapy, vitamin D intake, sun exposure and tanning bed use should be restricted. Fluconazole, an inhibitor of steroid hormone synthesis, has been used successfully to decrease serum calcium and 1,25(OH)2D, 17 although the tolerability and safety of such long-term therapy have not been established.…”

Section: Monogenic Causes Of Stone Diseasementioning

confidence: 99%

Personalized Intervention in Monogenic Stone Formers

et al. 2018

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Purpose Treatment of a first-time renal stone consists of acute management followed by medical efforts to prevent stone recurrence. Although nephrolithiasis is roughly 50% heritable, the presence of a family history usually does not affect treatment since most stone disease is regarded as polygenic, ie not attributable to a single gene. Recent evidence has suggested that single mutations could be responsible for a larger proportion of renal stones than previously thought. This intriguing possibility holds the potential to change the management paradigm in stone prevention from metabolically directed therapy to more specific approaches informed by genetic screening and testing. This review synthesizes new findings concerning monogenic kidney stone disease, and provides a concise and clinically useful reference for monogenic causes. It is expected that increased awareness of these etiologies will lead to increased use of genetic testing in recurrent stone formers and further research into the prevalence of monogenic stone disease. Materials and Methods We assembled a complete list of genes known to cause or influence nephrolithiasis based on recent reviews and commentaries. We then comprehensively searched PubMed® and Google Scholar™ for all research on each gene having a pertinent role in nephrolithiasis. We determined which genes could be considered monogenic causes of nephrolithiasis. One gene, ALPL, was excluded since nephrolithiasis is a relatively minor aspect of the disorder associated with the gene (hypophosphatasia). We summarized selected studies and assembled clinically relevant details. Results A total of 27 genes were reviewed in terms of recent findings, mode of inheritance of stone disease, known or supposed prevalence of mutations in the general population of stone patients and specific therapies or considerations. Conclusions There is a distinct opportunity for increased use of genetic testing to improve the lives of pediatric and adult stone patients. Several genes first reported in association with rare disease may be loci for novel mutations, heterozygous disease and forme frustes as causes of stones in the broader population. Cases of idiopathic nephrolithiasis should be considered as potentially having a monogenic basis.

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“…CYP24A1 mutations have now been proven in a cohort of adults presenting with nephrolithiasis, hypercalciuria, nephrocalcinosis and intermittent hypercalcaemia [4]. These patients had undergone extensive investigations before the cause of their nephrolithiasis was known, and multiple stone episodes and nephrocalcinosis may lead to progressive chronic kidney disease (CKD) [7]. This is important in highlighting the potential clinical spectrum of the phenotype, which may manifest without the trigger of vitamin D exposure.…”

Section: Adult Nephrolithiasismentioning

confidence: 99%

“…These would include maintaining a high fluid intake and avoiding excess dietary sodium. Specific measures would include avoiding dietary vitamin D supplements (in foods and drinks) and avoidance of excessive sunlight exposure [7]. Ketoconazole was first demonstrated as an effective treatment for reducing the effects of vitamin D toxicity in patients with CYP24A1 mutations.…”

Section: Treatmentmentioning

confidence: 99%

“…More recently, low-dose fluconazole, also acting as a P450 enzyme inhibitor, has been shown to reduce serum calcium levels and urinary calcium excretion in a patient with CYP24A1 mutation. It is likely that this drug, alongside lifestyle modifications such as avoiding excess sun exposure and following a low calcium and oxalate diet, will become the main treatment offered to patients diagnosed with CYP24A1 mutations (Figure 2) [7,18,19]. …”

Section: Treatmentmentioning

confidence: 99%

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Clinical and Biochemical Features of Patients with CYP24A1 Mutations

Hill¹,

Sayer²

2017

A Critical Evaluation of Vitamin D - Basic Overview

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The CYP24A1 gene encodes 1,25-hydroxyvitamin-D 3 -24-hydroxylase, a key enzyme responsible for the catabolism of active vitamin D (1,25-dihydroxyvitamin D 3 ). Loss-offunction mutations in CYP24A1 lead to increased levels of active vitamin D metabolites. Clinically, two distinct phenotypes have been recognised from this: infants with CYP24A1 mutations present with infantile idiopathic hypercalcaemia, often precipitated by prophylactic vitamin D supplementation. A separate phenotype of nephrolithiasis, hypercalciuria and nephrocalcinosis often presents in adulthood. CYP24A1 mutations should be suspected when a classical biochemical profile of high active vitamin D metabolites, high or normal serum calcium, high urine calcium and low parathyroid hormone is detected. Successful treatment with fluconazole, a P450 enzyme inhibitor, has been shown to be effective in individuals with CYP24A1 mutations. Although CYP24A1 mutations are rare, early recognition can prompt definitive diagnosis and ensure treatment is commenced.

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Successful treatment of hypercalcaemia associated with aCYP24A1mutation with fluconazole: Fig. 1.

Cited by 84 publications

References 9 publications

Vitamin D status including 3-epi-25(OH)D3 among adult patients with thyroid disorders during summer months

Vitamin D status including 3-epi-25(OH)D3 among adult patients with thyroid disorders during summer months

Personalized Intervention in Monogenic Stone Formers

Clinical and Biochemical Features of Patients with CYP24A1 Mutations

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