Cri du Chat
Cri du chat syndrome is a rare genetic disorder which approximately affects 1 in 20,000 to 50,000 live births. The disease does not depend on ethnic backgrounds, but is most common in the case of women.

The disorder gets its name from the typical cry of babies born with this syndrome. The baby sounds like a kitten, because of problems with the nervous system and larynx. The good news is that about 1/3 of kids recover by the age of 2. Negative aspects of this disease may be: * Feeding problems, because they can't suck and swallow well * Low weight at birth and poor evolution * Motor, cognitive, and speech delays * Behavioral problems such as aggression, hyperactivity, and repetitive movements * Uncommon facial traits that can change in time

* What is Cri-du-Chat syndrome?
The name of this syndrome is French for "cry of the cat," referring to the distinctive cry of children with this disorder. The cry is caused by abnormal larynx development, one of the many symptoms associated with this disorder. It usually becomes less noticeable as the baby gets older, making it difficult for doctors to diagnose cri-du-chat after age two. Cri-du-chat is caused by a deletion (the length of which may vary) on the short arm of chromosome 5. Multiple genes are missing as a result of this deletion, and each may contribute to the symptoms of the disorder. One of the deleted genes known to be involved is TERT (telomerase reverse transcriptase). This gene is important during cell division because it helps to keep the tips of chromosomes (telomeres) in tact. * How do people get Cri-du-Chat syndrome? * A deletion is caused by a break in the DNA molecule that makes up a chromosome. In most cases, the chromosome break occurs while the sperm or egg cell (the male or female gamete) is developing. When this gamete is fertilized, the child will develop cri-du-chat syndrome. The parent, however, does not have the break in any other cells of the body and does not have the syndrome. In fact, the break is usually such a rare event that it is very unlikely to happen again if the parent has another child. * It is possible for a child to inherit a broken chromosome from a parent who also had the disorder. * What are the symptoms of Cri-du-Chat syndrome?

Babies with cri-du-chat are usually small at birth, and may have respiratory problems. Often, the larynx doesn't develop correctly, which causes the signature cat-like cry. * People who have cri-du-chat have very distinctive features. They may have a small head (microcephaly), an unusually round face, a small chin, widely set eyes, folds of skin over their eyes, and a small bridge of the nose. * Several problems occur inside the body, as well. A small number of children have heart defects, muscular or skeletal problems, hearing or sight problems, or poor muscle tone. As they grow, people with cri-du-chat usually have difficulty walking and talking correctly. They may have behavior problems (such as hyperactivity or aggression), and severe mental retardation. If no major organ defects or other critical medical conditions exist, life expectancy is normal. * How do doctors diagnose cri-du-chat syndrome? * Doctors most often identify cri-du-chat by the infant's cat-like cry. Other signs are microcephaly, poor muscle tone, and mental retardation. * It is also possible to test for cri-du-chat (and other chromosomal abnormalitites) while the baby is still in its mother's womb. They can either test a tiny sample of tissue from outside the sac where the baby develops (chorionic villus sampling (CVS)), or they can test a sample of the amniotic fluid (amniocentesis). * How is cri-du-chat syndrome treated? * Although there is no real treatment for cri-du-chat syndrome, children with the disorder can go through therapy to improve their language skills, motor skills, and to help them develop as normally as possible. * Interesting facts about cri-du-chat syndrome * The geneticist Jerome Lejeune identified cri-du-chat syndrome in 1963. He also discovered the genetic abnormality that causes Down syndrome. * Cri-du-chat is one of the most common syndromes caused by a chromosomal deletion. It affects between 1 in 20,000 and 1 in 50,000 babies. * In 80 percent of the cases, the chromosome carrying the deletion comes from the father's sperm rather than the mother's egg. * When deletions occur during the formation of an egg or sperm, it is caused by unequal recombination during meiosis. Recombination normally occurs between pairs of chromosomes during meiosis while they are lined up at the metaphase plate. If the pairs of chromosomes don't line up correctly, or if the chromosome breaks aren't repaired properly, the structure of the chromosome can be altered. When unequal recombination occurs at this location on chromosome 5, it causes cri-du-chat syndrome.

What is Gaucher disease?
Gaucher disease is an inherited disorder that affects many of the body's organs and tissues. The signs and symptoms of this condition vary widely among affected individuals. Researchers have described several types of Gaucher disease based on their characteristic features.
Type 1 Gaucher disease is the most common form of this condition. Type 1 is also called non-neuronopathic Gaucher disease because the brain and spinal cord (the central nervous system) are usually not affected. The features of this condition range from mild to severe and may appear anytime from childhood to adulthood. Major signs and symptoms include enlargement of the liver and spleen (hepatosplenomegaly), a low number of red blood cells (anemia), easy bruising caused by a decrease in blood platelets (thrombocytopenia), lung disease, and bone abnormalities such as bone pain, fractures, and arthritis.
Types 2 and 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by problems that affect the central nervous system. In addition to the signs and symptoms described above, these conditions can cause abnormal eye movements, seizures, and brain damage. Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy. Type 3 Gaucher disease also affects the nervous system, but tends to progress more slowly than type 2.
The most severe type of Gaucher disease is called the perinatal lethal form. This condition causes severe or life-threatening complications starting before birth or in infancy. Features of the perinatal lethal form can include extensive swelling caused by fluid accumulation before birth (hydrops fetalis); dry, scaly skin (ichthyosis) or other skin abnormalities; hepatosplenomegaly; distinctive facial features; and serious neurological problems. As its name indicates, most infants with the perinatal lethal form of Gaucher disease survive for only a few days after birth.
Another form of Gaucher disease is known as the cardiovascular type because it primarily affects the heart, causing the heart valves to harden (calcify). People with the cardiovascular form of Gaucher disease may also have eye abnormalities, bone disease, and mild enlargement of the spleen (splenomegaly).
How common is Gaucher disease?
Gaucher disease occurs in 1 in 50,000 to 100,000 people in the general population. Type 1 is the most common form of the disorder, and occurs more frequently in people of Ashkenazi (eastern and central European) Jewish heritage than in those with other backgrounds. This condition affects 1 in 500 to 1,000 people of Ashkenazi Jewish heritage. The other forms of Gaucher disease are uncommon, and do not occur more frequently in people of Ashkenazi Jewish descent.
What genes are related to Gaucher disease?
Mutations in the GBA gene cause Gaucher disease.
The GBA gene provides instructions for making an enzyme called beta-glucocerebrosidase. This enzyme breaks down a fatty substance called glucocerebroside into a sugar (glucose) and a simpler fat molecule (ceramide). Mutations in the GBA gene greatly reduce or eliminate the activity of beta-glucocerebrosidase. Without enough of this enzyme, glucocerebroside and related substances can build up to toxic levels within cells. Tissues and organs are damaged by the abnormal accumulation and storage of these substances, causing the characteristic features of Gaucher disease.

Diagnosis
A definitive diagnosis is made with genetic testing. As there are numerous different mutations, sequencing of the beta-glucosidase gene is sometimes necessary to confirm the diagnosis. Prenatal diagnosis is available, and is useful when there is a known genetic risk factor.
A diagnosis can also be implied by biochemical abnormalities such as high alkaline phosphatase, angiotensin-converting enzyme (ACE) andimmunoglobulin levels, or by cell analysis showing "crinkled paper" cytoplasm and glycolipid-laden macrophages.
Some lysosomal enzymes are elevated, including tartrate-resistant acid phosphatase, hexosaminidase, and a human chitinase, chitotriosidase. This latter enzyme has proved to be very useful for monitoring Gaucher's disease activity in response to treatment, and may reflect the severity of the disease

Treatment
For type 1 and most type 3 patients, enzyme replacement treatment with intravenous recombinant glucocerebrosidase (imiglucerase) can dramatically decrease liver and spleen size, reduce skeletal abnormalities, and reverse other manifestations. This treatment costs approximately $200,000 annually for a single patient and should be continued for life. The rarity of the disease means that dose-finding studies have been difficult to conduct, so there remains controversy over the optimal dose and dosing frequency.[8] Due to the low incidence, this has become an orphan drug in many countries, meaning that a government recognizes and accommodates the financial constraints that limit research into drugs that address a small population.Velaglucerase alfa was approved by the Food and Drug Administration (FDA) as an alternative treatment on February 26, 2010.[11]
Successful bone marrow transplantation cures the non-neurological manifestations of the disease, because it introduces a monocyte population with active beta-glucosidase. However, this procedure carries significant risk and is rarely performed in Gaucher patients. Surgery to remove the spleen (splenectomy) may be required on rare occasions if the patient is anemic or when the enlarged organ affects the patient’s comfort. Blood transfusion may benefit some anemic patients. Other patients may require joint replacement surgery to improve mobility and quality of life. Other treatment options include antibiotics for infections, antiepileptics for seizures, bisphosphonates for bone lesions, and liver transplants. Substrate reduction therapy may prove to be effective in stopping Type 2, as it can cross through the blood barrier into the brain. There is currently no effective treatment for the severe brain damage that may occur in patients with types 2 and 3 Gaucher disease. Gene therapy may be a future step.
Gaucher's disease has recently become a target for more than one effort at pharmacological chaperoning, which involves the use of orally administered drugs that operate at a molecular level. Miglustat is one of these oral drugs. It was approved for the treatment of this disease in 2003. As of June 2009, another oral drug, isofagomine tartrate, is under development.