Oculocerebrorenal syndrome of Lowe

Mis-localisation of annexin 2 has recently been implicated in the pathogenesis of Dent s disease. This term is now used collectively to describe what was previously four conditions that affect kidney function X-linked recessive nephrolithiasis with renal failure, X-linked recessive hypophosphatemic rickets, idiopathic low molecular weight proteinuria with hypercalciuria and nephrocalcinosis and Dent s disease. Patients with this condition present with low molecular weight proteinuria and hypercalciuria. Renal stones, nephrocalcinosis and renal failure are common late-stage developments. The condition has been attributed to abnormal acidification within endosomes of the proximal tubular cells. It is very rare and is usually caused by mutations in the voltage-dependent Cl /H+ chloride antiporter CLCN5, but occasionally in the PI4,5P2 5-phosphatase, OCRL1 (oculocerebrorenal syndrome of Lowe protein 1). 

Arii T, Ohyanagi M, Shibuya J, Iwasaki T 1999 Increased function of the voltage-dependent calcium channels, without increase of Ca2+ release from the sarcoplasmic reticulum in the arterioles of spontaneous hypertensive rats. Am J Hypertens 12 1236-1242 Attree O, Olivos IM, Okabe I et al 1992 The Lowe s oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase. Nature 358 239-242 Brading AF, Turner WH 1994 The unstable bladder towards a common mechanism. Br J Urol 73 3-8... 

Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome. Am. J. Hum. Genet. 60 1384-1388. 

Two hereditary diseases, Fanconi s syndrome and Lowe s syndrome, are associated with tubular acidosis. The Fanconi syndrome is a multiple proximal tubular defect including interference with amino acid, glucose, and phosphate reabsorption. In most cases there is also acidosis that is proximal in origin, but the mechanism of the acidosis is unknown. Lowe s syndrome, or oculocerebrorenal syndrome, is transmitted in a sex-linked recessive fashion. Affected patients have the Fanconi syndrome and also mental retardation, cataracts, glaucoma, and hypotonia. 

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