Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal Fanconi syndrome (RFS) refers to the generalized dysfunction of the proximal tubule (PT) (Kleta R. Fanconi or not Fanconi? Lowe syndrome revisited. Clin J Am Soc Nephrol 2008; 3: 1244-1245). In its isolated form, RFS only affects the PT, but not the other nephron segments. The study of isolated RFS can thus provide specific insights into the function of the PT. In a recent paper, Klootwijk et al. investigated one such form of isolated RFS and revealed the underlying molecular basis (Klootwijk ED, Reichold M, Helip-Wooley A et al. Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome. N Engl J Med 2014; 370: 129-138). The affected family had been described previously, demonstrating the typical features of RFS, such as low-molecular weight proteinuria, aminoaciduria, glycosuria and phosphaturia with consequent rickets; yet, importantly, patients had no evidence of impaired glomerular filtration (Tolaymat A, Sakarcan A, Neiberger R. Idiopathic Fanconi syndrome in a family. Part I. Clinical aspects. J Am Soc Nephrol 1992; 2: 1310-1317). Inheritance was consistent with an autosomal dominant mode. Klootwijk et al. discovered a surprising explanation: a heterozygous missense mutation causing partial mistargeting of the peroxisomal enzyme EHHADH to the mitochondria. Notably, disease causing was not the absence of the enzyme in the peroxisome, but its interference with mitochondrial function. The discovery of this novel disease mechanism not only confirmed the importance of mitochondrial function for PT transport, but also demonstrated the critical dependence of PT on fatty acid metabolism for energy generation.
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PMID:Renal Fanconi syndrome: taking a proximal look at the nephron. 2549 94

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, 53 mL/min/1.73 m2). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.
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PMID:Adult Idiopathic Renal Fanconi Syndrome: A Case Report. 3089 10