Mucolipidosis
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robot Adding: [[it:Mucolipidosi]]
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ICD10 = {{ICD10|E|77|0|e|70}}-{{ICD10|E|77|1|e|70}} |
ICD9 = {{ICD9|272.7}} |
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MeshID = D009081 |
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'''Mucolipidosis''' ('''ML''') is a group of [[inherited]] [[metabolic disorder]]s that affect the body's ability to carry out the normal turnover of various materials within [[cell (biology)|cell]]s.
==Cause==
In ML, abnormal amounts of [[carbohydrate]]s or fatty materials ([[lipid]]s) accumulate in cells. Because our cells are not able to handle such large amounts of these substances, damage to the cells occurs, causing symptoms that range from mild [[learning disabilities]] to severe [[mental retardation]] and [[skeletal]] deformities. [[Symptoms]] of ML can be [[congenital]] (present at birth) or begin in [[early childhood]] or [[adolescence]]. Early symptoms can include [[Visual perception|vision]] problems and developmental delays. Over time, many children with ML develop poor mental capacities, have difficulty reaching normal developmental [[milestones]], and, in many cases, eventually die of the disease.
ML is classified as a [[lysosomal storage disease]] because it involves increased storage of substances in the [[lysosomes]], which are [[specialized]] sac-like components within most cells. Lysosomes play a critical role in the [[metabolic]] function of our bodies. One of their primary roles is to pick up substances such as carbohydrates and lipids and break them down into smaller [[molecules]] so that they can be used again in the metabolic process. This process is possible because lysosomes contain [[enzymes]], which are [[proteins]] that help the body’s [[chemistry]] work better and faster. Working continuously, enzymes break down carbohydrates and lipids and assist in the transfer of their byproducts throughout the rest of the cell for the production of [[energy]] or [[excretion]].
Patients with ML are born with a [[genetic defect]] in which their bodies either do not produce enough enzymes or, in some instances, produce ineffective forms of enzymes. Without functioning enzymes, which are proteins, lysosomes cannot break down carbohydrates and lipids and transport them to their normal destination. The molecules then accumulate in the cells of various [[Biological tissue|tissues]] in the body, leading to [[swelling]] and damage of organs. In patients with ML, the molecules accumulate in [[nerve]], [[liver]], and [[muscle]] tissue as well as in [[bone marrow]], and this abnormal storage causes the various symptoms associated with ML. For example, excess storage of these molecules in nerve tissues can cause mental retardation, accumulation in the tissues of the spleen and liver can cause poor functioning of these vital organs, and excess storage in the bone marrow can damage bones, leading to skeletal deformities.
The accumulation of carbohydrates and lipids in tissue is not the result of just one deficient enzyme. Lysosomes contain as many as 40 or 50 different enzymes, each responsible for a highly specialized function. Therefore, a deficiency in one particular enzyme or activator protein causes symptoms that may be somewhat different from the symptoms caused by the deficiency of another type of enzyme.
The MLs are similar to another group of lysosomal storage diseases known as the [[mucopolysaccharidoses]]. While both conditions produce similar symptoms and are caused by the lack of enzymes necessary to break down and transport carbohydrates and lipids, the mucopolysaccharidoses result in an excess of [[sugars]], known as mucopolysaccharides, in the [[urine]]. Mucopolysaccharides are not seen in urine of patients with ML, therefore screening of the urine can help doctors distinguish between the two groups of disorders.
== Types ==
There are four types of ML and each is classified according to the enzyme(s) or other protein that is deficient or mutated (altered). Symptoms can range from mild to severe.
The four types include [[sialidosis]] (sometimes referred to as ML I), and types II, III, and IV.
===ML I===
:''For details, see [[sialidosis]]''
'''Mucolipidosis type I''' (ML I) or '''sialidosis''' results from a deficiency in one of the [[digestive]] enzymes known as [[sialidase]].
===ML II and III===
:''For details, see [[I-cell disease]]'' (type II) and [[Pseudo-Hurler polydystrophy]] (type III)
Mucolipidosis types II and III (ML II and ML III) result from a deficiency of the enzyme [[N-acetylglucosamine-1-phosphotransferase]], which [[phosphorylate|phosphorylates]] target carbohydrate residues on N-linked [[glycoproteins]]. Without this phosphorylation, the glycoproteins are not destined for [[lysosomes]], and they escape outside the cell.
===ML IV===
:''For details, see [[Mucolipidosis type IV]]''
Mucolipidosis type IV (ML IV) is caused by harmful alterations of a protein in the cell that is believed to be involved in the movement of molecules such as calcium across cell membranes.
== Genetics ==
[[Image:Autorecessive.jpg|thumb|right|Mucolipidosis has an [[autosomal recessive]] pattern of inheritance.]]
The mucolipidoses are inherited in an [[autosomal]] [[recessive]] manner, that is, they occur only when a child inherits two copies of the defective gene, one from each parent. When both parents carry a defective gene, each of their children faces a one in four chance of developing one of the MLs. At the same time, each child also faces a one in two chance of inheriting only one copy of the defective gene. People who have only one defective gene are known as carriers. These individuals do not develop the disease but they can pass the defective gene on to their own children. Because the defective genes involved in certain forms of ML are known, tests can identify people who are carriers in some instances.
Scientists have identified the genes responsible for all four types of MLs. In 2000, scientists at [[NINDS]] laboratories and other research institutions identified the gene responsible for ML IV. This gene, MCOLN1, makes the protein mucolipin-1. Due to mutations in the gene, mucolipin-1 is missing or dysfunctional in people with ML IV. This important genetic finding allows for the accurate diagnosis of patients as well as [[prenatal]] (before birth) diagnosis and the screening of carriers of the disease.
[[Ashkenazi Jew]]s are frequent carriers of the disease<ref name="urlMount Sinai - Center for Jewish Genetic Diseases - Department of Human Genetics">{{cite web |url=http://www.mssm.edu/jewish_genetics/diseases/mucolipidosis.shtml |title=Mount Sinai - Center for Jewish Genetic Diseases - Department of Human Genetics |format= |work= |accessdate=}}</ref> when compared to other ethnic groups. A website states: "The frequency of MLIV in the general Jewish Ashkenazi population was estimated in a sample of 2,000 anonymous, unrelated individuals assayed for the two founder mutations. This analysis indicated a heterozygotes frequency of about 1/100".<ref name="urlWiley InterScience :: Session Cookies">{{cite web |url=http://www3.interscience.wiley.com/cgi-bin/abstract/79502195/ABSTRACT?CRETRY=1&SRETRY=0 |title=Wiley InterScience :: Session Cookies |format= |work= |accessdate=}}</ref>
== Diagnosis ==
The [[diagnosis]] of ML is based on clinical symptoms, a complete medical history, and certain [[laboratory]] tests. Diagnosis of ML I, II, and III can be confirmed by a [[blood test]] that measures enzyme activity in the patient's white blood cells. Activity levels that are lower than normal indicate specific enzyme deficiencies.
Another way to confirm the diagnosis is through skin [[biopsy]]. A small sample of skin is taken from the patient and grown in a cell culture. The activity of a particular enzyme in the cultured skin cells is then measured.
ML IV is suspected when cells that are easily obtained by [[conjunctival]] swabbing are found to have numerous inclusions. In addition, measurement of the level of gastrin in the blood, which is significantly increased in ML IV patients, helps to confirm the diagnosis.
Prenatal diagnosis for ML is accomplished using a procedure known as chorionic villus sampling, or CVS. It is usually done around the 8th or 10th week of pregnancy and involves removing and testing a very small sample of the placenta. For ML types I, II, and III, placental cells called amniocytes are grown in culture and then tested to measure enzyme activity levels. For ML IV, no culture is required. DNA is obtained directly from the [[amniocyte]]s and analyzed to find if [[mutations]] consistent with ML IV have occurred in the DNA. This technique is called [[genotyping]].
[[Genetic testing]] for ML IV is available at specialized laboratories. Genetic counselors can help explain how the MLs are inherited and the effect of these diseases on patients and their families. Counselors can also help adults who might have a defective gene decide whether or not they wish to have children. [[Psychological]] counseling and support groups for people with genetic diseases may also help patients and their families cope with ML.
== Treatment ==
No [[cure]] for ML currently exists. Therapies are generally geared toward treating symptoms and providing supportive care to the child. For individuals with corneal clouding, surgery to remove the thin layer over the eye has been shown to reduce the cloudiness in the eye.{{Fact|date=December 2007}} However, this improvement is only temporary. Physical and occupational therapy may help children with motor delays. Children with language delays may benefit from speech therapy.
Care also should be taken to maintain the overall health of patients with ML. For example, children at risk for failure to thrive (growth failure) may need [[nutritional supplements]], especially [[iron]] and [[vitamin B12]] for patients with ML IV. Respiratory infections should be treated immediately and fully with [[antibiotics]].
==References==
{{reflist}}
==See also==
* {{NINDS|mucolipidoses}}
{{Glycoproteinoses}}
[[Category:Lysosomal storage diseases]]
[[Category:Genetic disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Ashkenazi Jews topics]]
[[it:Mucolipidosi]]