Synonym: Lowe Syndrome
Inheritance: X-linked
Chromosome location affected: Xq26.1 (may involve a translocation with an autosome)
Gene mutation: OCR1 which encodes inositol polyphosphate 5-phosphatase OCRL-1
Key features:
(1) bilateral, dense, congenital cataracts
(2) generalized hypotonia
(3) Fanconi-type dysfunction of the proximal renal tubule with bicarbonate wasting, renal tubular acidosis, phosphaturia, aminoaciduria, low molecular weight proteinuria, polyuria, sodium wastage and potassium wastage
Additional findings:
(1) renal rickets with or without pathologic fractures
(2) developmental delay
(3) low normal to severe mental retardation
(4) visual impairment with or without infantile glaucoma and buphthalmos
(5) variable seizure disorder
(6) absent deep tendon reflexes (DTR)
(7) behavioral problems
(8) short stature
(9) hypercalciuria with nephrocalcinosis and renal stones
(10) dental abnormalities (cysts, dysplastic dentin)
(11) cutaneous cysts
(12) enlarged cerebral ventricles with periventricular cysts
(13) glomerulosclerosis with end-stage renal disease by early adulthood
(14) feeding problems during infancy with gastroesophageal reflux
(15) variable cryptorchidism
(16) hypermobile joints with joint dislocations and/or degenerative arthritis
Laboratory findings:
(1) < 10% of normal inositol polyphosphate 5-phosphatase OCRL-1 activity in cultured skin fibroblasts
(2) proteinuria affecting low molecular weight proteins
(3) positive for mutation by FISH or sequence analysis
