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Pediatr Nephrol. 2016 Dec;31(12):2201-2212. Epub 2016 Mar 24.

The oculocerebrorenal syndrome of Lowe: an update.

Author information

1
Department of Pediatric Nephrology, VU University Medical Center, de Boelelaan 1112, 1081 HV, Amsterdam, The Netherlands. a.bokenkamp@vumc.nl.
2
Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.

Abstract

The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, intellectual disability, and proximal renal tubular dysfunction. Whereas the ocular manifestations and severe muscular hypotonia are the typical first diagnostic clues apparent at birth, the manifestations of incomplete renal Fanconi syndrome are often recognized only later in life. Other characteristic features are progressive severe growth retardation and behavioral problems, with tantrums. Many patients develop a debilitating arthropathy. Treatment is symptomatic, and the life span rarely exceeds 40 years. The causative oculocerebrorenal syndrome of Lowe gene (OCRL) encodes the inositol polyphosphate 5-phosphatase OCRL-1. OCRL variants have not only been found in classic Lowe syndrome, but also in patients with a predominantly renal phenotype classified as Dent disease type 2 (Dent-2). Recent data indicate that there is a phenotypic continuum between Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for the loss of enzyme function. Extensive research has demonstrated that OCRL-1 is involved in multiple intracellular processes involving endocytic trafficking and actin skeleton dynamics. This explains the multi-organ manifestations of the disease. Still, the mechanisms underlying the wide phenotypic spectrum are poorly understood, and we are far from a causative therapy. In this review, we provide an update on clinical and molecular genetic findings in Lowe syndrome and the cellular and physiological functions of OCRL-1.

KEYWORDS:

Cognitive and behavioral impairment; Congenital cataract; Inositol-polyphosphate 5-phosphatase; OCRL gene; Oculocerebrorenal syndrome; Proximal tubulopathy; Renal Fanconi syndrome

PMID:
27011217
PMCID:
PMC5118406
DOI:
10.1007/s00467-016-3343-3
[Indexed for MEDLINE]
Free PMC Article

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