Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by 1,25(OH)(2)-vitamin D (1,25(OH)(2)D), dietary and circulating phosphate and possibly PTH. FGF23 was discovered as the humoral factor in tumors that causes hypophosphatemia and osteomalacia and through the identification of a mutant form of FGF23 that leads to autosomal dominant hypophosphatemic rickets (ADHR), a rare genetic disorder. FGF23 appears to be mainly secreted by osteocytes where its expression is up-regulated by 1,25(OH)(2)D and probably by increased serum phosphate levels. Its synthesis and secretion is reduced through yet unknown mechanisms that involve the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX), dentin matrix protein 1 (DMP1) and ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Consequently, loss-of-function mutations in these genes underlie hypophosphatemic disorders that are either X-linked or autosomal recessive. Impaired O-glycosylation of FGF23 due to the lack of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 3 (GALNT3) or due to certain homozygous FGF23 mutations results in reduced secretion of intact FGF23 and leads to familial hyperphosphatemic tumoral calcinosis. FGF23 acts through FGF-receptors and the coreceptor Klotho to reduce 1,25(OH)(2)D synthesis in the kidney and probably the synthesis of parathyroid hormone (PTH) by the parathyroid glands. It furthermore synergizes with PTH to increase renal phosphate excretion by reducing expression of the sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc in the proximal tubules. Loss-of-function mutations in these two transporters lead to autosomal recessive Fanconi syndrome or to hereditary hypophosphatemic rickets with hypercalciuria, respectively.
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PMID:FGF23 and syndromes of abnormal renal phosphate handling. 2239 61

Apremilast is a recently developed phosphodiesterase 4-inhibitory medication approved for use to treat psoriasis and psoriatic arthritis. We report a case of Fanconi syndrome and proximal renal tubular acidosis that was associated with this medication. Our patient was started on treatment with apremilast 2 weeks before his admission. On arrival, laboratory test results were significant for hypokalemia, hyperchloremic metabolic acidosis, low uric acid concentration, positive urine anion gap, and proteinuria, which resolved on discontinuation of the drug. Two months after the hospitalization, he was restarted on apremilast therapy; 17 days after resumption, the patient was admitted for similar laboratory values, which again improved when apremilast treatment was discontinued. After discharge, laboratory values remained normal without long-term electrolyte repletion. Proximal renal tubular acidosis (Fanconi syndrome) with quick correction of electrolyte concentrations on discontinuation of the drug was diagnosed. Our patient lacked evidence of other causes. Our patient fulfilled criteria associated with this disease and responded well off treatment with the offending agent. Literature review did not reveal prior cases associated with this medication.
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PMID:Proximal Renal Tubular Acidosis (Fanconi Syndrome) Induced by Apremilast: A Case Report. 2882 83