Lowe syndrome or oculo-cerebro-renal syndrome is a multisystem disease that associates a De Toni-Debré-Fanconi syndrome with severe mental retardation and congenital ocular and neurological diseases. The features are hydrophthalmia, cataract, mental retardation, vitamin D-resistant rickets, amino aciduria, and reduced ammonia production by the kidney.
Congenital cataracts are the basis for diagnosis. Some patients may develop bilateral glaucoma. Also, microphthalmia and enophthalmos and decreased visual acuity have been observed. In the first year of life intense hypotonia and hyporeflexia are observed, which are generally the first neurological manifestations. Up to 50% of the patients may have seizures. Most patients have a mild intellectual delay but their performance is compromised because they often exhibit behavioural disorders such as stubbornness, crisis of irritability and stereotyped movements. Impaired renal function, which consists of a proximal tubular dysfunction, is not always present at birth, but appears during the first year of life and manifests as failure to thrive.
Along with the clinical manifestations listed above there is proximal tubular acidosis, with loss of bicarbonate, amino acids and phosphate, polyuria and proteinuria. The hyperaminoaciduria is widespread and milder than in cystinosis. The phosphaturia can lead to rickets that if untreated may promote the development of pathologic fractures. In addition to renal tubular dysfunction, these patients have a decrease in creatinine clearance that eventually leads them to end-stage renal failure. Because of the allelic heterogeneity exhibited by the OCRL gene, prenatal diagnosis by molecular analysis is limited to families in which the mutation is already known. There is a more generally applicable diagnostic test based on biochemical testing (by measuring phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity in cultured amniocytes).
The inheritance pattern is X-linked recessive. The Lowe syndrome gene, OCRL, encodes a protein that has been termed OCRL. This protein is 51% identical to inositol polyphosphate 5-phosphatase. These results suggest that Lowe syndrome is an inborn error of inositol phosphate metabolism. This is the first human genetic disorder that affects this pathway. Abnormalities of metabolism or transport of inositol have been implicated in the pathogenesis of cataract and peripheral neuropathy in galactosemia and diabetes mellitus. Cells of patients with Lowe syndrome have a high concentration of phosphatidylinositol 4,5-bisphosphate, the substrate of the protein OCRL. A cellular anomaly in actin cytoskeleton has been demonstrated in fibroblasts from patients with Lowe syndrome. For the genetic study it will be necessary samples of the index case and the parents.
Treatment is symptomatic. Ocular defects should be treated as soon as possible because they prevent the child to get a full performance of its possibilities. Control of renal function must be very strict. Water intake should be increased to compensate for urinary losses and alkaline salts should be administered when bicarbonatemia levels are below 20 mEq / l. Supplemental phosphate should be monitored with the ion levels and with the bone turnover markers as both the clinical and the radiological findings of rickets are delayed.
It is severe due to blindness, mental retardation and the ability to develop into a chronic kidney disease.
Complications are those already described, ie, cataracts, glaucoma, nystagmus, rubbing eyes, severe mental retardation, muscular hypotonia, diffuse demineralization and rickets (due to Fanconi syndrome) and the ability to develop into a chronic kidney disease.