Lowe's syndrome (Charles Lowe, born 1921, American paediatrician), (also called oculocerebral renal syndrome), is an X-linked recessive disorder, affecting males. Initially recognized in 1952, by Lowe, Terry and McLahan who described the triad of congenital cataracts, mental retardation and generalized aminoaciduria. The probable gene site is Xq24-36 and probable aetiopathogenesis is an inborn error of inositol phosphate metabolism.
There have been approximately 150 reported cases. It affects males of Caucasian or Asian ancestry. Primary clinical manifestations include: congenital cataracts, cognitive impairment, and renal tubular dyfunction (Fanconis syndrome). Secondary clinical features include areflexia, hypotonia, glaucoma, corneal keloid, and noninflammatory joint swelling. The affected children are short in stature, likely due to renal disease. Deaths related to renal failure, dehydration, and recurrent infections have been reported. Characteristic lens opacities are seen in female carriers of the abnormal gene.
The primary biomedical defects remain indeterminate. In affected individuals, renal failure usually occurs in the third decade. Classically, there are three phases of renal disease. In phase I (in utero gestation to infancy), few specific clinical or morphologic manifestations are seen. Phase II (infancy to childhood) consists primarily of tubular dysfunction with little glomerular damage. In phase III (adulthood), renal glomerular disease predominates, and tubular dysfunction improves owing to decreased glomerular filtration. More recent studies show that subtle biochemical abnormalities are present even in stage I of the disease, including proteinuria, aminoaciduria, and low urine osmolality.
Diagnosis is based largely on the constellation of clinical findings and laboratory results. Radiographic findings are those of renal tubular dysfunction. On excretory urography, tubular dysfunction results in decreased concentrating ability.
Cranial MR findings consist of diffuse supratentorial white matter abnormalities. These are of two types. One variety is multiple small spherical foci in deep and subcortical white matter with signal characteristics paralleling that of CSF on all three spin-echo sequences. The other variety consists of confluent areas of abnormal signal intensity diffusely involving the white matter with extension to subcortical surface. These areas are slightly hypointense on T1-weighted images and are hyperintense on both proton density and T2-weighted images. The smaller punctate lesions may represent focal areas of encephalomalacia secondary to a remote insult, while the confluent lesions may be focal areas of gliosis or demyelination.
Therapy consists of replacement of renal losses and supportive care, such as physical therapy, special education and ophthalmological intervention in cases of cataracts and glaucoma. Because of progressive phosphaturia, early phosphate supplementation prior to the development of hypophosphataemia or actual rickets is recommended. This early intervention is important to maintain bony integrity. Vitamin D administration is helpful in increasing the intestinal absorption of phosphate in younger patients and providing vitamin supplementation in older patients with renal failure. Patients also benefit from alkalinization of urine and supplementation of potassium, phosphate, calcium, and possibly carnitine.
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