The CYP24A1 gene encodes 1,25-hydroxyvitamin-D3-24-hydroxylase, a key enzyme responsible for the catabolism of active vitamin D (1,25-dihydroxyvitamin D3). Loss-of-function 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.
Part of the book: A Critical Evaluation of Vitamin D
Cystinuria is a rare inherited renal stone disease. Mutations in two genes SLC3A1 and SLC7A9 underlie this condition, encoding proteins that facilitate dibasic amino acid exchange which are expressed in the gut and the proximal tubule of the kidney. Genetic studies now allow precise genotyping of patients who may have both autosomal dominant and autosomal recessive patterns of disease. The disorder is characterised by the urinary loss of cystine, lysine, ornithine, and arginine, and the insolubility of cystine gives rise to crystalluria and cysteine-containing renal stones. Although an inherited condition, it may present at any age. Clinical management combines lifestyle advice and preventative medical therapy. However, many patients require surgical interventions to remove problematic stones from the urinary tract. Preventative therapies include increased fluid intake, alkalinization of the urine, and the use of cystine-binding drugs, including penicillamine and tiopronin, which form soluble heterodimers with cystine.
Part of the book: Updates and Advances in Nephrolithiasis