Oculocerebrorenal syndrome (also called Lowe syndrome) is a rare

X-linked Sex linkage describes the sex-specific patterns of inheritance and expression when a gene is present on a sex chromosome (allosome) rather than a non-sex chromosome ( autosome). Genes situated on the X-chromosome are thus termed X-linked, and ...

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 it is a potential manifestation of many different dis ...

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

, proximal tubular

acidosis Acidosis is a biological process producing hydrogen ions and increasing their concentration in blood or body fluids. pH is the negative log of hydrogen ion concentration and so it is decreased by a process of acidosis. Acidemia The term ac ...

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, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become fo ...

. 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 t ...

(bicarbonaturia, renal tubular acidosis,

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

loss and

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

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 of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or double vision, halos around ligh ...

in both eyes;

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

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 many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

, 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 bioche ...

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

organic acids An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids, whose acidity is associated with their carboxyl group –COOH. Sulfonic acids, containing the group –SO2OH, are r ...

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

and

L-carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids from the cytosol into mitochondria to be oxidized for fre ...

. This problem is known as Fanconi-type renal tubular dysfunction.

Genetics

This syndrome is caused by mutations in the ''

OCRL Inositol polyphosphate 5-phosphatase OCRL-1, also known as Lowe oculocerebrorenal syndrome protein, is an enzyme encoded by the ''OCRL'' gene located on the X chromosome in humans. This gene encodes an inositol polyphosphate 5-phosphatase. The ...

'' 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 Rab may refer to: Places * Rab (island), an island in Croatia * Rab (town), on the island of Rab * Ráb, the Slovak name of Győr, a city in Hungary * Rąb, a village in Poland People * Rab (surname), includes a list of people with the n ...

-binding

domain A domain is a geographic area controlled by a single person or organization. Domain may also refer to: Law and human geography * Demesne, in English common law and other Medieval European contexts, lands directly managed by their holder rather ...

. This protein is associated with the primary

cilia The cilium (: cilia; ; in Medieval Latin and in anatomy, ''cilium'') is a short hair-like membrane protrusion from many types of eukaryotic cell. (Cilia are absent in bacteria and archaea.) The cilium has the shape of a slender threadlike proj ...

of the

retinal pigment epithelial The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual ...

cells,

fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...

s and kidney 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 File:Oculo-Cerebro-Renal Syndrome 1.jpg, Another Infant with Lowe Syndrome File:X-linked recessive.svg, X-link recessive inheritance

Diagnosis

Diagnosis of oculocerebrorenal syndrome can be done via

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

Among the different investigations that can be done are: *

Urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a Test panel, panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and #Microscopic examination, m ...

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

Blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

test

Treatment

In terms of treatment of oculocerebrorenal syndrome for those individuals who are affected by this condition includes the following: *

Glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

control (via medication) *

Nasogastric tube Nasogastric intubation is a medical process involving the insertion of a plastic tube (nasogastric tube or NG tube) through the nose, down the esophagus, and down into the stomach. Orogastric intubation is a similar process involving the insertion ...

feeding *

Physical therapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

Clomipramine Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most notably obsessive–compulsive disorder but also many other disorders, including hyper ...

Potassium citrate Potassium citrate (also known as tripotassium citrate) is a potassium salt of citric acid with the molecular formula K3C6H5O7. It is a white, hygroscopic crystalline powder. It is odorless with a saline taste. It contains 38.28% potassium by mass ...

Epidemiology

Because oculocerebrorenal syndrome is an

X-linked recessive ''Main Article'': Sex linkage X-linked recessive inheritance is a mode of Mendelian inheritance, inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily hemizygous for ...

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 (1921–2012) and colleagues at the

Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is a teaching hospital located in the West End neighborhood of Boston, Massachusetts. It is the original and largest clinical education and research facility of Harvard Medical School/Harvar ...

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