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Gaucher disease : Causes, Types, Symptoms, Diagnosis and Treatment

 What is Gaucher disease?

Gaucher disease is an associate degree transmissible disease. It causes bone pain, anemia, enlarged organs, a swollen, painful belly and bruising and hurt issues. There are 3 types of sickness. Some sorts of Gaucher sickness will cause severe brain injury and death. However, Gaucher sickness sort one (the commonest within the U.S.) is treatable.

Gaucher sickness may be a rare, transmissible disorder within which deficiency of the accelerator glucocerebrosidase ends up in the buildup of harmful quantities of bound fats (lipids), specifically the glycolipid glucocerebroside, throughout the body particularly inside the bone marrow, spleen and liver. The symptoms and physical findings related to Gaucher sickness vary greatly from patient to patient. Some people develop few or no symptoms (asymptomatic); others might have serious complications.


Common manifestations of Gaucher sickness embody associate degree abnormally enlarged liver and/or spleen (hepatosplenomegaly), low levels of current red blood cells (anemia), low levels of platelets (thrombocytopenia), and skeletal abnormalities. Platelets are unit blood cells that promote curdling and patients with blood disorders might develop hurt issues. 3 separate varieties of Gaucher sickness are known and area units distinguished by the absence of, or the presence and extent of, neurologic complications. All 3 varieties of Gaucher sickness area unit transmissible in associate degree chromosome recessive pattern.

Gaucher sickness is classified as a lysosomal storage disorder (LSD). Lysosomes are the key biological process units in cells. Enzymes inside lysosomes break down or “digest” nutrients, together with bound complicated carbohydrates and fats. In Gaucher sickness bound sugar (glucose) containing fat, referred to as glycolipids, abnormally accumulate within the body thanks to the shortage of the accelerator, glucocerebrosidase. This accumulation or “storage” of lipids ends up in the assorted symptoms or physical findings related to a lysosomal storage sickness. Gaucher sickness is the second commonest variety of lysosomal storage disorder. (Recent publications indicate that Fabry sickness is the most prevailing LSD).


What is Gaucher disease



Explanation of medical terms and concept Gaucher disease

Gaucher (go-SHAY) disease is the result of a buildup of bound fatty substances in bound organs, significantly your spleen and liver. This causes these organs to enlarge and might have an effect on their performance.

The fatty substances can also build up in bone tissue, weakening the bone and increasing the chance of fractures. If the bone marrow is affected, it will interfere along with your blood's ability to clot.

A catalyst that breaks down these fatty substances does not work properly in folks with Gaucher unwellness. Treatment typically includes catalyst replacement medical care.

An inherited disease, Gaucher unwellness is most typical in folks of jap and Central European descent (Ashkenazi). Symptoms will seem at any age. 

Gaucher disease is an inherited disorder It occurs when the body’s cells are unable to process a substance called glucocerebroside (GC) This substance provides energy for cells and the body’s organs People with Gaucher disease lack important enzymes that help break down certain substances in the body These substances build up and eventually damage organs especially the liver spleen and bone marrow The accumulation of these substances also leads to abnormally high numbers of white blood cells red blood cells platelets and other abnormal blood cell types White blood cell counts can be so high that they.

and You Gaucher disease is a genetic condition and it affects millions of people It is caused by mutations in the GBA gene which causes an abnormal buildup of lipids and other substances inside cells People with Gaucher disease have fewer blood platelets than normal which makes them more prone to bleeding and bruising easily The condition can also cause bone abnormalities nerve damage lung disease and enlarged internal organs.

Types Gaucher disease

Their square measures 3 styles of Gaucher illness (pronounced go-shay). All cause similar symptoms within the organs and bones. Some sorts of the illness conjointly have an effect on the brain. the categories of Gaucher illness are:

  • Gaucher disease type 1: The most common sort within the U.S., Gaucher illness sort one affects the spleen, liver, blood and bones. It doesn't have an effect on the brain or neural structure. Gaucher illness is treatable, however there's no cure. For a few folks, symptoms square measure delicate. people experience severe bruising, fatigue and pain, particularly within the bones and belly. Symptoms will seem at any age, from childhood to adulthood. 

  • Gaucher disease type 2: A rare style of the disorder, kind two seems in babies underneath six months previous. It causes associate degree enlarged spleen, movement issues and severe brain injury. there's no treatment for Gaucher illness kind two. Babies with this condition expire within 2 to 3 years. 

  • Gaucher disease type 3: Worldwide, Gaucher malady is the most typical kind, however it’s rare within the u. s ... It seems before age ten and causes bone and organ abnormalities and neurologic (brain) issues. Treatments will facilitate many of us with Gaucher malady kind three living into their 20s or 30s. 

Symptoms Gaucher disease

Researchers have known 3 distinct kinds of Gaucher malady separated by the absence (type 1) or presence and extent (type a pair of or sort 3) of neurologic complications. extra kinds of Gaucher malady embrace perinatal-lethal type and vessel type. The precise symptoms given in people with Gaucher malady vary greatly from person to person. Some people exhibit few or no symptoms (asymptomatic); others expertise chronic, and typically severe, complications.

Gaucher malady sort one is additionally called non-neuronopathic, as a result of it doesn't involve the central system (brain and spinal cord). sort one Gaucher malady is that the most typical kind of the condition. most people with Gaucher malady sort one expertise simple bruising because of low levels of clotting cells called platelets (thrombocytopenia), chronic fatigue because of low levels of current red blood cells (anemia), associate degreed an abnormally enlarged liver and/or spleen (hepatosplenomegaly). Affected people may expertise lack of blood provide (infarction) to numerous bones of the body leading to boring or intense bone pain (bone crises), degeneration (avascular necrosis) and deformity of affected bones, and cutting and weakening of bones (osteoporosis). Such skeletal abnormalities lead to associate degree exaggerated status to fractures. In rare cases, affected people may experience involvement of the lungs and/or kidneys.

Gaucher malady, sort of a pair of, conjointly called acute neuronopathic Gaucher malady, happens in newborns and infants and is characterized by neurologic complications because of the abnormal accumulation of glucocerebroside within the brain. Enlargement of the spleen (splenomegaly) is usually the primary symptom and will become apparent before six months archaic. Enlargement of the liver (hepatomegaly) isn't forever evident. Affected infants might lose antecedently non-inheritable motor skills and exhibit low tonus (hypotonia), musculus spasms (spasticity) that lead to slow, stiff movements of the arms and legs, and crossed eyes (strabismus). additionally, affected infants might expertise problem swallowing (dysphagia), which can lead to feeding difficulties; abnormal positioning or bending of the neck (retroflexion); and failure to achieve weight and grow at the expected rate (failure to thrive) and high-pitched respiration (stridor) because of contraction of the muscles of the cartilaginous structure (laryngeal spasm). Anemia and blood disease may occur. Gaucher malady sort a pair of usually progresses to dangerous complications like metastasis distress or the doorway of food into the metastasis passages (aspiration pneumonia). Severely affected newborns might show skin abnormalities (collodion skin or ichthyosiform changes) and generalized swelling (hydrops), with death within the initial few weeks of life. Different kids with Gaucher may sort a pair of have greatly reduced lifespans, with death typically occurring between one and three years of life.

Gaucher malady sort three, conjointly called chronic neuronopathic Gaucher malady, happens throughout the primary decade of life. In addition to the blood and bone abnormalities mentioned higher than, affected people develop neurologic complications that develop and progress slower than in Gaucher may sort a pair of. Associated neurologic complications embrace mental deterioration; associate degree inability to coordinate voluntary movements (ataxia); and temporary, shock-like muscle spasms of the arms, legs or entire body (myoclonic seizures). Some people with Gaucher malady sort three might have problems moving their eyes from the area (horizontal gaze palsy). Patients with sort three Gaucher malady may have a vertical gaze palsy that sometimes happens later than the horizontal gaze palsy. a major proportion of patients conjointly develop respiratory organ (lung) malady (interstitial respiratory organ disease). There is often wide variability in presentation and clinical course among patients with sort three Gaucher malady. Some affected patients might live into their teens and early 20’s, whereas others have lived for much longer (30’s and 40’s). With increasing difficulties, affected people might need help to meet the task of daily living (for example, with feeding, bathing, and ambulation).

The perinatal-lethal type or fetal/neonatal Gaucher malady happens in but five-hitter of patients. This kind is extremely severe and related to death before three months, archaic or maybe within the uterus. The fetus/newborn might be gifted with widespread swelling of the skin (edema or anasarca) resulting in fluid buildup within the heart, skin, or lungs (hydrops fetalis). different symptoms embrace hemorrhage at intervals the bone (intracranial hemorrhage), scaling of the skin (non-bullous ichthyosiform erythroderma) with a cherry look, and contraction of the joints in mounted, bent position (arthrogryposis multiplex congenita).

The vessel type is characterized by central nervous system involvement, like having problems initiating eye movement in desired directions (oculomotor apraxia). Different symptoms embrace calcification of the mitral and semilunar valve, membrane opacity, and gentle hypertrophy. metallic element deposits on the center will scale back blood flow to those valves, and may increase pressure. Supranuclear palsy may be a gift that causes issues with balance, walking, and thinking. Cardiac-related complications and associated neurological issues result in a reduced life, though this may extend into young adulthood in some patients.

There square measure differing kinds of Gaucher malady, and signs and symptoms of malady vary wide, even at intervals of constant sort. sort one is out and away the foremost common.

Siblings, even identical twins, with the malady will have totally different levels of severity. Some those who have Gaucher malady have solely gentle or no symptoms.

Most people who have Gaucher disease have varying degrees of the following problems:

  • Abdominal complaints. Because the liver and especially the spleen can enlarge dramatically, the abdomen can become painfully distended.

  • Skeletal abnormalities. Gaucher disease can weaken bone, increasing the risk of painful fractures. It can also interfere with the blood supply to your bones, which can cause portions of the bone to die.

  • Blood disorders. A decrease in healthy red blood cells (anemia) may end up in severe fatigue. Gaucher sickness conjointly affects the cells chargeable for curdling, which might cause simple bruising and nosebleeds.
    More seldom, Gaucher sickness affects the brain, which might cause abnormal eye movements, muscle rigidity, swallowing difficulties and seizures. One rare subtype of Gaucher sickness begins in infancy and generally leads to death by a pair of years older. 

When to see a doctor

If you or your kid has the signs and symptoms related to Gaucher sickness, build an arrangement along with your doctor.

Causes Gaucher disease

Gaucher disease is passed along in an inheritance pattern called autosomal recessive. Both parents must be carriers of a Gaucher changed (mutated) gene for their child to inherit the condition.

Gaucher sickness is caused by changes (mutations) within the GBA cistron.

All 3 varieties of Gaucher sickness square measure inheritable in Associate in Nursing chromosome recessive pattern. Human traits, as well as the classic genetic diseases, square measure the merchandise of the interaction of 2 genes, one received from the daddy and one from the mother.

Recessive cistrontic disorders occur once a personal inherits Associate in Nursing abnormal gene from every parent. If a person receives from every parent one traditional cistron and one abnormal cistron for the sickness, the person is going to be a carrier for the sickness, however typically won't show symptoms. The chance for 2 carrier folks to each pass the abnormal cistron and, therefore, have an Associate in Nursing affected kid is twenty fifth with every gestation. the chance to own a baby World Health Organization could be a carrier, just like the folks, is five hundredth with every gestation. the possibility for a baby to receive traditional genes from each folks is twenty fifth. The chance is the same for males and females.

Gaucher sickness is Associate in Nursing inheritable upset. It’s passed down through families. folks with Gaucher sickness don’t have enough of the Associate in Nursing catalyst referred to as glucocerebrosidase (GCase). Enzymes like GCase square measure proteins that perform many tasks, as well as breaking down fats (sphingolipids) within the body.

If the body doesn’t have enough of those enzymes, fatty chemicals (called Gaucher cells) build up within the organs, bone marrow and brain. The surplus fats cause a good variety of issues and symptoms. They have an effect on however the organs work, and that they destroy blood cells and weaken bones.

Risk factors Gaucher disease

People of Eastern and Central European Jewish (Ashkenazi) ancestry are at higher risk of developing the most common variety of Gaucher disease.

Complications

Gaucher disease can result in:

  • Delays in growth and puberty in children

  • Gynecological and obstetric problems

  • Parkinson's disease

  • Cancers such as myeloma, leukemia and lymphoma

Diagnosis Gaucher disease

A designation of Gaucher illness ought to be thought-about in people with unexplained anemia and straightforward bruising, significantly if they need enlargement of the spleen and liver and fractures. The designation of Gaucher illness is also confirmed by a radical clinical analysis and a range of specialized tests, significantly tests (i.e., protein assay) that live acid beta-glucosidase activity in white blood cells (leukocytes) or skin cells (fibroblasts) and sequencetic (DNA) analysis for the causative gene defects (mutations). Note: the protein check cannot dependably find carriers.

The protein assay check is thought to be a BGL (beta-glucosidase leukocyte) biopsy. This can be a typical tool employed by physicians to diagnose somebody UN agency is assumed to possess Gaucher illness, as a result of typically these patients having low glucocerebrosidase protein activity. If the results area unit slightly low, the individual would be then referred by the medico to endure sequencetic testing for mutations within the GBA gene. Genetic testing is completed via blood or spit. Identification of 2 causative sequence defects, in conjunction with protein check results, confirms the designation of Gaucher illness. People in whom solely one sequence defect is known is also a carrier or, within the presence of low beta-glucosidase, is also affected with a second sequence defect (mutation) not detected. Referral to AN applicable genetic specialist is also indicated during this state of affairs. desoxyribonucleic acid analysis identifies people UN agencies carry a mutation within the GBA sequence UN agency will pass the mutation to youngsters.

Prenatal diagnosis of Gaucher illness is feasible if a celebrated GBA point mutation is a gift within the family. Testing may be done through amnio or villus sampling (CVS), however is unusual unless there's a case history of Gaucher illness kind of a pair of. Throughout amnio, a sample of fluid that surrounds the vertebrate (amniotic fluid) is removed and analyzed, whereas CVS involves the removal of tissue samples from a little of the placenta. {prenatal designation|diagnostic procedure|diagnostic technique} will make sure a precise diagnosis of Gaucher illness however doesn't confirm the sort of illness.

During a physical examination, your doctor can prolong your or your child's abdomen to see the scale of the spleen and liver. to see if your kid has Gaucher illness, the doctor can compare your child's height and weight to standardized growth charts.

He or she may additionally advocate sure research lab tests, imaging scans and counseling.

Lab tests

Blood samples can be checked for levels of the enzyme associated with Gaucher disease. Genetic analysis can reveal whether you have the disease.

Imaging Tests

People diagnosed with Gaucher unwellness generally need periodic tests to trace its progression, including:

  • Dual energy X-ray absorptiometry (DXA). This test uses low-level X-rays to measure bone density.

  • MRI. Using radio waves and a strong magnetic field, an MRI can show whether the spleen or liver is enlarged and if bone marrow has been affected.

Preconception screening and prenatal testing

You might wish to think about screening before beginning a family if you or your partner is of Ashkenazi Jewish heritage or if either of you have got a case history of Gaucher unwellness. In some cases, doctors advocate antenatal testing to examine if the vertebrate is in danger of Gaucher unwellness.

Treatment Gaucher disease

The main goal is to enhance the patients’ quality of life by permitting them to perform their traditional daily activities, like operating while not feeling the surplus fatigue or walking ordinarily while not experiencing joint pain. Different goals embrace preventing the severity of complications, like reduced bone density to dilution, weak bones (osteoporosis) and simple fractures or shortness of breath from the reduced respiratory organ. Normalizing the expansion for a toddler for them to achieve a traditional height may be a target among some of years of treatment and achieving a traditional onset of pubescence.

Treatment is personalized for every patient betting on the sort of Gaucher unwellness. sort one Gaucher unwellness is taken into account treatable and delicate, as a result of it doesn't involve neurologic symptoms since the brain isn't affected. sort two isn't thought of to be treatable at this time because of the fast and irreversible brain injury within the infantile years. sort three still involves neurologic injury, however these symptoms progress a lot more slowly than in sort two. There are currently FDA-approved drug medical care choices that embrace protein replacement medical care (ERT) and substrate reduction medical care (SRT).

Enzyme replacement medical care (ERT) has proved effective for people with Gaucher unwellness. In studies of coordinated universal time, anemia and low protoplasm counts have improved, enlargement of the liver and spleen are greatly reduced, and skeletal findings have improved. These general manifestations conjointly improve in people with Gaucher unwellness varieties two and three WHO receive coordinated universal time. However, coordinated universal time has not been effective in reducing or reversing neurologic symptoms related to Gaucher unwellness varieties two and three.

ERT is given each two weeks via blood vessel (IV) infusions either at infusion centers, National Gaucher Unwellness Treatment Center, or reception by self-administration, with help from a family member/friend or home care nurse. The 3 current FDA-approved coordinated universal time medicines embrace imiglucerase (Cerezyme), velaglucerase alfa (VPRIV), and taliglucerase (Elelyso).

The orphan drug alglucerase injection (Ceredase), that may be a placenta-derived protein, was approved by the U.S. Food and Drug Administration (FDA) in one991 for the treatment of Gaucher unwellness sort 1. It absolutely was the primary coordinated universal time proved effective for the treatment of Gaucher unwellness.

The artificial type of this drug, imiglucerase (Cerezyme), was approved in 1994. recombinant deoxyribonucleic acid technology, or gene-splicing, is employed to supply Cerezyme. This was a vital step in overcoming limitations of the supply of Ceredase, which comes from human placentas. Therefore, Ceredase has been withdrawn from the market because of similar medicine being created while not having bioavailability problems from human derived cells and also the transfer of diseases. Cerezyme, factory-made by Genzyme, replaces the human lysosomal protein glucocerebrosidase that's lacking in people with Gaucher unwellness.

Another bureau approved preparation of glucocerebrosidase referred to as Velaglucerase alfa (trade name VPRIV) created during a continuous human cell line is out there from Shire.

Elelyso (also referred to as Uplyso or taliglucerase alfa) by Pfizer INC., under license from Protalix BioTherapeutics INC., was approved by the bureau in 2012 as a treatment for Gaucher unwellness. Elelyso is associate degree-injected long-run protein replacement medical care that ought to be administered by a health care specialist each different week. It uses genetically designed carrot cells to supply replacement glucocerebrosidase.

Substrate reduction medical care can also be used in specific patient populations. These work otherwise than the ERT’s by obstructing the assembly of glucocerebroside (fatty substance) by inhibiting the protein glucosylceramide synthase. These are available in tablets/capsules and area units taken daily. SRT’s aren't to be employed in youngsters and teenagers, pregnant or breastfeeding girls, senior patients, and folks with severe urinary organs or disease. The 2 current FDA-approved medicines embrace eliglustat (Cerdelga) and miglustat (Zavesca).

In 2014, Cerdelga (eliglustat), factory-made by Genzyme, was approved by the bureau for the long-run treatment of adult patients with the Gaucher unwellness sort one.

In 2003, the U.S. Food and Drug Administration approved Zavesca, associate degree oral medical care, for the treatment of adult patients with delicate to moderate Gaucher unwellness sort one for whom protein replacement medical care isn't a treatment choice (as a results of allergic reaction, hypersensitivity, etc.).

Genetic counseling is usually recommended for affected people and their families. A different treatment is symptomatic and subsidiary.

There is current analysis at the Medical biological science Branch of the National Human order analysis Institute a few potential links or associations between Gaucher unwellness and Parkinson unwellness. Studies have shown that affected people (with 2 unwellness-causing GBA factor mutations) associate degreed carriers (with one GBA factor mutation) each have an exaggerated risk of Parkinson disease.

Individuals with Gaucher unwellness are at an exaggerated risk for myeloma, and as adults ought to be monitored rigorously.

While there is not any cure for Gaucher unwellness, a range of treatments will facilitate management symptoms, stop irreversible injury and improve quality of life. Some individuals have such delicate symptoms that they do not like treatment.

Your doctor seemingly can suggest routine watching to observe for unwellness progression and complications. however typically {you'll need|you can need|you'll have} to be monitored depending upon your state of affairs.

Medications

Many people UN agency have Gaucher unwellness have seen enhancements in their symptoms when starting treatment with:

  • Enzyme replacement therapy. This approach replaces the deficient protein with artificial ones. These replacement enzymes square measure given in Associate in Nursing patient procedure through a vein (intravenously), usually in high doses at two-week intervals. Often folks have Associate in Nursing allergic or hypersensitivity to protein treatment. 

  • Miglustat (Zavesca). This oral medication appears to interfere with the production of fatty substances that build up in people with Gaucher disease. Diarrhea and weight loss are common side effects.

  • Eliglustat (Cerdelga). This drug additionally appears to inhibit the assembly of fatty substances that build up in individuals with the foremost common style of Gaucher malady. attainable aspect effects embody fatigue, headache, nausea and symptoms. 

  • Osteoporosis drugs. These types of medication can help rebuild bone weakened by Gaucher disease.

Surgical and other procedures

If your symptoms are severe and you are not a candidate for fewer invasive treatments, your doctor would possibly suggest:

  • Bone marrow transplant. In this procedure, blood-forming cells that are broken by Gaucher unwellness are removed and replaced, which might reverse several of Gaucher signs and symptoms. As a result of this can be an insecure approach, it's performed less typically than is accelerator replacement medical aid. 

  • Spleen removal. Before enzyme replacement therapy became available, removing the spleen was a common treatment for Gaucher disease. Now this procedure typically is used as a last resort.

Coping and support

Having any chronic malady will be troublesome, however having a rare illness like Gaucher will be even tougher. Few folks understand the illness, and even fewer perceive the challenges you face. you would possibly realize it useful to speak to somebody else. The World Health Organization has Gaucher illness or somebody World Health Organization features a kid with the illness. seek advice from your doctor regarding support teams in your space.

Preparing for your appointment

You're able to start out by seeing your medical aid supplier. Then you may be observed a doctor World Health Organization makes a speciality of blood disorders (hematologist) or to a doctor World Health Organization makes a speciality of genetic disorders (geneticist).

What you can do

Before the appointment, you may want to write a list of answers to the following questions:

  • Has anyone in your family been diagnosed with Gaucher disease?

  • Have any children in your extended family died before the age of 2 years?

  • What medications and supplements do you take regularly?

What to expect from your doctor

Your doctor might ask questions, including:

  • What are the symptoms, and when did they begin?

  • Is there pain in the abdomen or bones?

  • Have you noticed easy bruising or nosebleeds?

  • What's your family's ancestral heritage?

  • Are there diseases or symptoms that have occurred in several generations in your family?

General summary

Gaucher disease is a serious genetic disorder that occurs when the enzyme glucocerebrosidase is missing or defective This enzyme breaks down chemicals in cells called glucocerebroside and plays an important role in the immune system growth and development Without sufficient levels of this enzyme harmful amounts of these chemicals build up in the body's organs.

How long can you live with Gaucher disease?

Gaucher disease is a rare inherited disorder that causes an individual to have unusually high levels of lipids and fatty substances in the blood There are two forms of the condition; type 1 is characterized by a buildup of lipids in the spleen liver or bone marrow and type 2 is marked by lipid deposits under the skin People who have Gaucher disease may also experience pain in their bones joints and muscles due to damaged nerve cells Proponents of enzyme replacement therapy claim it helps individuals with Gaucher disease live longer than they would without treatment; however there is no definitive proof that this form of treatment helps.

What happens to people with Gaucher disease?

Gaucher disease is a genetic disorder that affects specific cell types within the bone marrow leading to low levels of an enzyme called glucocerebrosidase People with Gaucher disease slowly lose their ability to produce blood cells white blood cells and platelets over time which causes tissue damage throughout the body Symptoms include bone abnormalities and spinal curvature skin rashes and painful enlargement of the spleen or liver.

Is Gaucher disease serious?

Gaucher disease is serious but treatable Early diagnosis and treatment can often prevent more serious complications from occurring Treatment for Gaucher involves infusions of medication that help the body break down fatty molecules known as glucocerebrosidase which accumulate in large amounts in people with Gaucher disease These infusions are typically given two to three times per week.

How common is Gaucher?

Gaucher disease is a rare disorder that affects about one in 50,000 people worldwide The disease occurs equally in males and females and has no racial or ethnic preference Although Gaucher can develop at any age it most often appears in middle-aged to elderly adults Approximately 1 in 3 people with Gaucher are being diagnosed before the age of 20 years; however symptoms may not be recognized until later on Since Gaucher disease is inherited as an autosomal recessive condition both parents of an affected child must carry a defective gene for the child to be born with Gaucher Therefore each pregnancy represents a risk.

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Gaucher disease : Causes, Types, Symptoms, Diagnosis and Treatment

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