Oculocerebrorenal syndrome (also called Lowe syndrome) is a rare

X-linked Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...

recessive disorder characterized by congenital cataracts,

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...

, proximal tubular

acidosis Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describes ...

aminoaciduria Aminoaciduria occurs when the urine contains abnormally high amounts of amino acids. In the healthy kidney, the glomeruli filter all amino acids out of the blood, and the renal tubules then reabsorb over 95% of the filtered amino acids back into ...

and low-molecular-weight

proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...

. Lowe syndrome can be considered a cause of

Fanconi syndrome Fanconi syndrome or Fanconi's syndrome (, ) is a syndrome of inadequate reabsorption in the proximal renal tubules of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity (for example, from tox ...

(bicarbonaturia, renal tubular acidosis,

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosph ...

loss and

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

loss).

Signs and symptoms

Boys with Lowe syndrome are born with

cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...

in both eyes;

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

is present in about half of the individuals with Lowe syndrome, though usually not at birth. While not present at birth, kidney problems develop in many affected boys at about one year of age. Renal pathology is characterized by an abnormal loss of certain substances into the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

, including

bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial biochem ...

, amino acids, organic acids, albumin, calcium and L-carnitine. This problem is known as Fanconi-type renal tubular dysfunction.

Genetics

This syndrome is caused by mutations in the ''OCRL'' gene which encodes an inositol polyphosphate-5-phosphatase. At least one mechanism by which these mutations cause this syndrome is by loss of its Rab (G-protein), Rab-binding Protein domain, domain. This protein is associated with the primary cilia of the retinal pigment epithelial cells, fibroblasts and kidney Nephron, tubular cells. This suggests that this syndrome is due to dysfunction of the cilia in these cells. About 120 mutations are associated with this condition and ''OCRL'' gene which is associated with oculocerebrorenal syndrome

Diagnosis

Diagnosis of oculocerebrorenal syndrome can be done via genetic testing Among the different investigations that can de done are: * Urinalysis * MRI * Blood test

Treatment

In terms of treatment of oculocerebrorenal syndrome for those individuals who are affected by this condition includes the following: * Glaucoma control (via medication) * Nasogastric tube feeding * Physical therapy * Clomipramine * Potassium citrate

Epidemiology

Because oculocerebrorenal syndrome is an X-linked recessive condition, the disease develops mostly in men with very rare occurrences in women, while women are carriers of the disease; it has an estimated prevalence of 1 in 500,000 people.

History

It was first described in 1952 by American paediatrician Charles Upton Lowe (August 24, 1921 – February 9, 2012) and colleagues at the Massachusetts General Hospital in Boston. Because of the three major organ systems involved (eyes, brain and kidney), it is known as oculocerebrorenal syndrome.

References

External links

{{Authority control Amino acid metabolism disorders X-linked recessive disorders Syndromes affecting the eye Syndromes affecting the kidneys