- Author: Deborah M Alcorn, MD; Chief Editor: Hampton Roy, Sr, MD more...
Oculocerebrorenal syndrome (OCRS) is an X-linked recessive metabolic disorder described by Lowe and coworkers in 1952. It is a multisystem disorder that primarily affects the eyes, nervous system, and kidneys. It is characterized by congenital cataracts, infantile glaucoma, neonatal or infantile hypotonia, intellectual impairment, and renal tubular dysfunction (Fanconi syndrome).
The oculocerebrorenal syndrome is so named because of the prominent involvement of the 3 major organ systems; however, involvement of bone, gonads, muscle, skin, and connective tissue, as well as stereotypic behavior, also can occur. Additional manifestations include corneal keloids, growth retardation, areflexia, metabolic acidosis, proteinuria, aminoaciduria, and noninflammatory arthropathy. These patients often exhibit the characteristic facial appearance of frontal bossing, deep set eyes, and full cheeks, although the characteristic phenotype is often difficult to identify in neonates.
Female carriers manifest characteristic lens opacities, but they typically have normal renal and neurologic function. See the image below.
OCRL is caused by a mutation of the OCRL1 gene mapped to the chromosomal locus of Xq26.1. The gene encodes a phosphatidylinositol (4,5) bisphosphate 5 phosphatase, localized to the trans-Golgi complex involved in actin polymerization.[2, 3] It is a key enzyme in the cellular phosphoinositide pathway, important in cellular trafficking. Deficiency of the enzyme causes the protean manifestations of Lowe syndrome. The reduced enzyme activity results in increased enzyme substrate and abnormal actin-binding proteins important in neuronal morphogenesis.[4, 5]
The estimated prevalence is 1/500,000.
See the list below:
- Ocular: The hallmark feature is congenital cataracts. Left untreated, the cataracts will cause nystagmus and eventual blindness. Glaucoma develops in 50-70% of patients, typically manifesting in the first year of life, but it may present at any age. Patients also may develop corneal leukomas. Amblyopia may occur secondary to poor compliance with treatment and secondary strabismus. Corrected visual acuity is infrequently better than 20/70 despite optimal management. The visual impairment represents a combination of the morphologic changes in the eye, retinal dysfunction, and cortical functioning.
- Renal: If untreated, the proximal renal tubular acidosis leads to failure to thrive and metabolic collapse. By the second to third decade, gradual loss of creatinine clearance occurs, with progressive renal failure.
- Growth: At birth, these patients are within the normal growth curve but fall off in length, height, and weight in subsequent years.
- Neurological: Neonatal hypotonia may contribute to poor feeding and delayed motor development.
- Life expectancy: Patients with appropriate therapy may live to be 30-40 years of age, generally dying from renal failure, respiratory distress, status epilepticus, or infection. With improved medical treatment, infection as a cause for death has declined dramatically. The expected life span has not yet been defined.
Oculocerebrorenal syndrome occurs almost exclusively in males. It is an X-linked recessive disorder. The female carrier state is identifiable by characteristic lenticular opacities.
A few cases have been reported in females, often having X-autosome translocations involving the OCRL1 locus, explained by the inactivation of the normal X chromosome by the translocation.
Oculocerebrorenal syndrome is congenital.
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