Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts, renal Fanconi syndrome, and mental retardation.
The oculocerebrorenal syndrome is characterized by failure to thrive and the triad of renal tubular acidosis, congenital cataracts, and mental retardation. The renal dysfunction is characterized by bicarbonate wasting, aminoaciduria, phosphaturia, and proteinuria coupled with a defect in urinary concentration. Furthermore, the cells secrete abnormally large amounts of lysosomal hydrolases.
Synopsis
systemic anomalies
ocular anomalies
- congenital cataract (males)
- glaucoma
- microphthalmia
- corneal keloid
- fine lens opacities (carrier females)
- dense, posterior cortical cataract (carrier females)
dental anomalies
- enlarged dental follicles
- dental follicular cyst
- enamel hypoplasia
cryptorchidism
renal failure
joint hypermobility
osteomalacia
renal rickets
skeletal anomalies
- scoliosis
- kyphosis
- patyspondyly
- hip dislocation
- genu valgum
- finger swelling
- wrist swelling
tenosynovitis
flexion contractures of the digits
cutaneous appendages tumors
- sebaceous cysts (buttocks and perineum)
- eruptive vellus hair cysts
subcutaneous nodules (fingers)
ventriculomegaly
periventricular cysts
proximal renal tubular acidosis
renal Fanconi syndrome
In female heterozygotes: opthalmologic abnormalities
- multiple, micropunctate, gray lens opacities
- single, dense posterior cataract
sporadic tumor description
- retinoblastoma (10779271)
- acinic cell carcinoma of the parotid gland (9125068)
Etiology
mutations in the OCRL1 gene, which encodes a phosphatidylinositol-4,5 bisphosphate-5-phosphatase located in the trans-Golgi network (PIP(2)-5-phosphatase deficiency). This anomaly affects actin polymerization. (12428211)
- also mutated in the Dent syndrome
Physiopathology
The gene mutated in the syndrome encodes a protein, OCRL-1, an inositol polyphosphate 5-phosphatase that catalyzes the conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate.
The clinical findings suggest that the OCRL-1 protein regulates the transport of lysosomal hydrolases and other proteins by controlling the concentrations of phosphatidylinositol 4,5-bisphosphate in lysosomal or Golgi membranes.
The severity of the symptoms underscores the recently uncovered central role of polyphosphoinositide lipids in membrane transport.
References
Pendaries C, Tronchere H, Plantavid M, Payrastre B. Phosphoinositide signaling disorders in human diseases. FEBS Lett. 2003 Jul 3;546(1):25-31. PMID: 12829232
Olkkonen VM, Ikonen E. Genetic defects of intracellular-membrane transport. N Engl J Med. 2000 Oct 12;343(15):1095-104. PMID: 11027745