The oculocerebrorenal syndrome of Lowe: an update
- PMID: 27011217
- PMCID: PMC5118406
- DOI: 10.1007/s00467-016-3343-3
The oculocerebrorenal syndrome of Lowe: an update
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.
Conflict of interest statement
Compliance with ethical standards Conflict of interests The authors declare that they have no conflict of interest.
Figures
![Fig. 1](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/5118406/bin/467_2016_3343_Fig1_HTML.gif)
![Fig. 2](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/5118406/bin/467_2016_3343_Fig2_HTML.gif)
![Fig. 3](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/5118406/bin/467_2016_3343_Fig3_HTML.gif)
Similar articles
-
Lowe syndrome/Dent-2 disease: A comprehensive review of known and novel aspects.J Pediatr Genet. 2013 Jun;2(2):53-68. doi: 10.3233/PGE-13049. J Pediatr Genet. 2013. PMID: 27625841 Free PMC article. Review.
-
Complete oculocerebrorenal phenotype of Lowe syndrome in a female patient with half reduction of inositol polyphosphate 5-phosphatase.CEN Case Rep. 2020 May;9(2):95-100. doi: 10.1007/s13730-019-00434-z. Epub 2019 Nov 9. CEN Case Rep. 2020. PMID: 31707643 Free PMC article.
-
OCRL deficiency impairs endolysosomal function in a humanized mouse model for Lowe syndrome and Dent disease.Hum Mol Genet. 2019 Jun 15;28(12):1931-1946. doi: 10.1093/hmg/ddy449. Hum Mol Genet. 2019. PMID: 30590522 Free PMC article.
-
Lowe Syndrome.2001 Jul 24 [updated 2019 Apr 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2001 Jul 24 [updated 2019 Apr 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301653 Free Books & Documents. Review.
-
The 5-phosphatase OCRL in Lowe syndrome and Dent disease 2.Nat Rev Nephrol. 2017 Aug;13(8):455-470. doi: 10.1038/nrneph.2017.83. Epub 2017 Jul 3. Nat Rev Nephrol. 2017. PMID: 28669993 Review.
Cited by
-
Atypical phenotypes and novel OCRL variations in southern Chinese patients with Lowe syndrome.Pediatr Nephrol. 2024 Aug;39(8):2377-2391. doi: 10.1007/s00467-024-06356-y. Epub 2024 Apr 8. Pediatr Nephrol. 2024. PMID: 38589698
-
Congenital Malformations of the Eye: A Pictorial Review and Clinico-Radiological Correlations.J Ophthalmol. 2024 Jan 30;2024:5993083. doi: 10.1155/2024/5993083. eCollection 2024. J Ophthalmol. 2024. PMID: 38322500 Free PMC article. Review.
-
Primary cilia and actin regulatory pathways in renal ciliopathies.Front Nephrol. 2024 Jan 16;3:1331847. doi: 10.3389/fneph.2023.1331847. eCollection 2023. Front Nephrol. 2024. PMID: 38292052 Free PMC article. Review.
-
Fetal and Placental Causes of Elevated Serum Alpha-Fetoprotein Levels in Pregnant Women.J Clin Med. 2024 Jan 14;13(2):466. doi: 10.3390/jcm13020466. J Clin Med. 2024. PMID: 38256600 Free PMC article. Review.
-
A Case of Hidradenitis Suppurativa in a Genetically Confirmed Lowe Syndrome Patient.Ann Dermatol. 2023 Nov;35(Suppl 2):S314-S316. doi: 10.5021/ad.22.131. Ann Dermatol. 2023. PMID: 38061729 Free PMC article.
References
-
- Lowe CU, Terrey M, Mac LE. Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity. AMA Am J Dis Child. 1952;83:164–184. - PubMed
Publication types
MeSH terms
Supplementary concepts
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical