A rare disease a day: Lowe Syndrome

In honor of rare disease day later this week, I am raising awareness of some of the rare diseases as brief posts. Following on from past installments of “A rare disease a day” Hunter syndrome, Gaucher disease, Tay-Sachs, Morquio syndrome, Fabry disease, Sanfilippo syndrome, Krabbe Disease, Niemann-Pick Disease, Batten disease , Hurler Syndrome, Charcot-Marie-Tooth, Fibromuscular dysplasia, Huntington’s disease,  Giant Axonal Neuropathy (GAN). Neuroendocrine tumor, Amyloidosis it is now the turn of Lowe syndrome

Lowe Syndrome (also known as Oculocerebrorenal syndrome, OCRS)  severely affects the brain, eyes, kidneys, bones and muscles, leading to physical and mental impairment.  It is a rare ( estimated prevalence of 1 in 500,000 people)  X-linked recessive disorder characterized by congenital cataracts, hypotonia and areflexia, mental retardation, proximal tubular acidosis, aminoaciduria, phosphaturia, and low-molecular-weight proteinuria. Glaucoma is present in about 50% of cases. Lowe syndrome can be considered a cause of Fanconi syndrome (bicarbonaturia, renal tubular acidosis, aminoaciduria, phosphaturia, tubular proteinuria, and impaired urine-concentrating ability). While the disease is seen in males from early childhood currently there is no cure.

This syndrome is caused by mutations in the OCRL1 gene which encodes a inositol polyphosphate-5-phosphatase. At least one reported mechanism by which these mutations cause this syndrome is by loss of its Rab binding domain. This protein is associated with the primary cilia of the retinal pigment epithelial cells, fibroblasts and kidney tubular cells. This suggests that this syndrome is due to dysfunction of the cilia in these cells. A crystal structure of OCRL1 and Rab8 was published in 2012. This study also suggested the OCRL1/Rab8 module could be involved in neurite outgrowth and synaptic transmission which shape the nervous system. Defects in primary cilia formation occur in Bardet- Biedl syndrome or polycystic kidney disease as well. A zebrafish model of Lowe syndrome could be used to screen for treatments e.g. gene therapy etc, while a knock-out (OCRL1) mouse also exists.

The longest reported survival of a patient with the disease as of 2006 was a 54 year old. Some useful patient support groups can be found at Rare Connect.


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