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'' describe ...

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 atmos ...

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 ...

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 aqueous humor, fluid withi ...

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. Cellul ...

, 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 biochemi ...

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

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 the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...

calcium Calcium is a chemical element with the 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 ...

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 into mitochondria to be oxidized for energy production, an ...

. 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 The enzyme Inositol-polyphosphate 5-phosphatase (EC 3.1.3.56, systematic name 1D-''myo''-inositol-1,4,5-trisphosphate 5-phosphohydrolase; other names type I inositol-polyphosphate phosphatase, inositol trisphosphate phosphomonoesterase, InsP3/Ins(1 ...

. At least one mechanism by which these mutations cause this syndrome is by loss of its

Rab Rab �âːb( dlm, Arba, la, Arba, it, Arbe, german: Arbey) is an island in the northern Dalmatia region in Croatia, located just off the northern Croatian coast in the Adriatic Sea. The island is long, has an area of and 9,328 inhabitants (2 ...

-binding

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined ** Domain of definition of a partial function ** Natural domain of a partial function **Domain of holomorphy of a function * ...

. This protein is associated with the primary

cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike proje ...

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 biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...

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

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 de done are: *

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

* MRI *

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 in the cir ...

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 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 aqueous humor, fluid withi ...

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 oesophagus, and down into the stomach. Orogastric intubation is a similar process involving the inserti ...

feeding *

Physical therapy Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, pat ...

* Clomipramine *

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 X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily homozygous for the gene mutation because they have one X and one Y ...

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 Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...

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