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The estimated prevalence is 1/500,000 and males are almost exclusively affected.

Oculocerebrorenal syndrome of Lowe (OCRL) is a congenital disorder characterized by ocular abnormalities (bilateral congenital discoid cataracts, glaucoma with or without buphthalmos, strabismus, hypermetropia and corneal and conjunctival cheloids), neurological involvement (developmental delay, seizures, hypotonia present at birth typically with absence of deep tendon reflexes), stereotypic behavior (temper tantrums, aggressiveness and obsessive compulsive behavior), postnatal growth retardation, mild to severe intellectual disability (mean IQ 40-50), stereotypic hand movements, renal dysfunction of the Fanconi type (proximal tubular acidosis; phosphate wasting leading to renal rickets, osteomalacia and pathological fractures) and progressive decline in kidney function leading to end-stage renal failure in adulthood. Subtle cataracts are obligate findings in female carriers after puberty. Other clinical manifestations include facial dysmorphism (frontal bossing, deep-set eyes, chubby cheeks, fair complexion), destructive teno-synovitis in older patients, short stature, mucocutaneous anomalies (eruptive vellus hair cysts, tricoepithiloma, excess skin folds and eruption cysts in oral cavity), dental malformations, cryptorchidism and bleeding tendency due to platelet dysfunction.

OCRL results from mutations in OCRL (Xq25), leading to phosphatidylinositol (4,5) bisphosphate accumulation, defective membrane trafficking and disturbed actin cytoskeleton remodeling. In the kidney, disturbed endosomal trafficking impairs protein reabsorption and digestion in the proximal tubules. In the eye, abnormal actin remodeling leads to disorganization of embryonic lens epithelium and abnormal development of the trabecular meshwork that regulates aqueous humor outflow from the eye.

Diagnosis of OCRL is based on specific ophthalmologic, neurologic and renal abnormalities. Laboratory findings reveal features of renal Fanconi syndrome and elevations in plasma creatine kinase, lactate dehydrogenase and transaminases levels. The presence of low-molecular weight proteinuria is the first renal abnormality and is invariably present after birth. Brain imaging reveals brain atrophy, delayed myelination, pachygyrias, hydrocephalus as well as white matter lesions suggestive of periventricular leukomalacia. Diagnosis is confirmed by genetic screening of OCRL.

Differential diagnosis includes Dent disease type 2 (an allelic disease with a milder phenotype), congenital infections (such as congenital rubella syndrome), Nance-Horan syndrome, Smith-Lemli-Opitz syndrome, muscle-eye-brain disease, cystinosis and peroxisomal disorders.

Prenatal testing is possible and unless the mutation in the family has been defined previously, assay of enzyme activity is preferred. Elevated maternal serum and amniotic fluid alpha-fetoprotein or presence of cataract on ultrasound may be used for prenatal screening.

The pattern of inheritance is X-linked and genetic counseling is recommended for affected families. If the mother is a carrier, 50% of her sons will inherit the disease whereas 50% of her daughters will be carriers. De novo mutations are reported in 30% of affected males.

Treatment of OCRL includes early cataract extraction to avoid amblyopia, glaucoma control by either medications or surgery and postoperatively, eye glasses. Contact lenses are contraindicated. Nasogastric tube feedings or feeding gastrostomy may be required. Treatment also includes physical and speech therapy, use of drugs (clomipramine, paroxetine and risperidone) for behavioral problems, correction of tubular dysfunction by alkali supplements, phosphate, potassium and water. Potassium citrate may be useful to prevent nephrocalcinosis.

Quality of life depends on extent of neurological and renal manifestations. Life span rarely exceeds 40 years and death occurs between 20-40 years, as a consequence of renal disease, hypotonia, increased susceptibility to infectious disease, seizures and sudden death. Glaucoma is often difficult to control.