General description

Lowe syndrome, also known as oculocerebrorenal syndrome of Lowe (OCRL), is a rare X-linked multisystemic disorder characterized by the classical triad of congenital cataracts, neurological impairment, and renal tubular dysfunction. Lowe syndrome is caused by mutations in the OCRL gene located on chromosome Xq26.1, which encodes an inositol polyphosphate 5-phosphatase (OCRL-1). This enzyme preferentially cleaves phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) to generate PI 4P. OCRL-1 is predominantly expressed in the brain and localizes to the trans-Golgi network, lysosomes, and endosomes.

Males with this condition are born with dense cataracts in both eyes, which develop before birth and are always present at birth. Other common eye issues include small eyes, sunken appearance, glaucoma in about half of the patients during early life, and corneal scarring or keloids in a quarter of cases.

Neurologically, affected individuals are born with reduced muscle tone due to central nervous system involvement, often lacking deep tendon reflexes. Although some improvement may occur with age, normal strength is not achieved. Motor development is delayed, with many boys beginning to walk independently between early childhood and adolescence. Intellectual disability is a key feature, ranging from mild to profound severity. About half experience seizures, and behavioral problems such as repetitive movements, self-harm, and aggression are frequently observed. Laboratory tests often reveal mildly elevated muscle-related enzyme levels.

Kidney problems involve dysfunction of the proximal tubules, resembling Fanconi syndrome. All patients show protein loss in the urine, and many have abnormalities in handling amino acids, phosphate, potassium, and calcium. Some develop acid buildup due to impaired kidney function. Glucose handling is usually less affected. Around half develop calcium deposits in the kidneys, and kidney failure tends to occur in early to mid-adulthood.

References

1. Carroll, William J., William W. Woodruff, and Thomas E. Cadman. "MR findings in oculocerebrorenal syndrome." American journal of neuroradiology 14.2 (1993): 449-451.