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Gaucher Disease

Gaucher's Disease

Gaucher disease is a lysosomal storage disease in which enzyme deficiency leads to accumulation of glycolipids in various tissues, mainly in the monocyte-macrophage system. It is transferred by autosomal recessive pattern of inheritance and depending on the subtype, patients may present with hepatosplenomegaly, anemia, neurological deficits and many other. The diagnosis is made by bone marrow biopsy and genetic testing, while enzyme replacement therapy is used with great success.

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Presentation

Patients with GD may present at a different age and clinical subtypes are [3]:

The diagnosis of GD cannot be made solely on clinical criteria, which is why laboratory and imaging studies are used to make the diagnosis.

Easy Bruising
  • Hematological Easy Bruising Gaucher Disease [GBA]: Enlargement of spleen and liver, blood abnormalities (anemia, easy bruising, impaired clotting, etc), and bone problems (joint pain, bone fractures, etc).[symptoma.com]
  • Type 1 - Beta glucocerebrosidase deficency - most common adult type easy bruising Anaemia , Fx treatable w enzyme replacement therapy ( fatal if enzyme subsitute is not given) Type 2 ( infantile) Lethal by age 3 brain and organ involvement untreated Type[brainscape.com]
  • Other symptoms may include: Bone pain and fractures Cognitive impairment (decreased thinking ability) Easy bruising Enlarged spleen Enlarged liver Fatigue Heart valve problems Lung disease (rare) Seizures Severe swelling at birth Skin changes Gaucher[nlm.nih.gov]
  • Gaucher Disease [GBA]: Enlargement of spleen and liver, blood abnormalities (anemia, easy bruising, impaired clotting, etc), and bone problems (joint pain, bone fractures, etc). Variable age of onset and severity of symptoms.[jewishgeneticdiseases.org]
  • bruising Slow or stunted growth in children Intestinal problems like abdominal swelling Trouble breathing Seizures Vision problems Developmental delays In type II, rigidity and seizures may appear within the first few months of life.[uvahealth.com]
Splenomegaly
  • CONCLUSION: HALS for GD patients with refractory hypersplenism and massive splenomegaly is safe and feasible in experienced hands.[ncbi.nlm.nih.gov]
  • [ncbi.nlm.nih.gov] Massive Splenomegaly CONCLUSION: HALS for GD patients with refractory hypersplenism and massive splenomegaly is safe and feasible in experienced hands.[symptoma.com]
  • In symptomatic patients, splenomegaly is progressive and can become massive. Children with massive splenomegaly may be short in stature because of the energy expenditure required by the enlarged organ.[emedicine.medscape.com]
  • Mean final values for patients with severe splenomegaly ( n 6), moderate‐to‐severe anemia ( n 6), or severe thrombocytopenia ( n 8) were similar to patients with milder disease at baseline and within long‐term therapeutic goal thresholds.[doi.org]
Massive Splenomegaly
  • CONCLUSION: HALS for GD patients with refractory hypersplenism and massive splenomegaly is safe and feasible in experienced hands.[ncbi.nlm.nih.gov]
  • [ncbi.nlm.nih.gov] Massive Splenomegaly CONCLUSION: HALS for GD patients with refractory hypersplenism and massive splenomegaly is safe and feasible in experienced hands.[symptoma.com]
Anemia
  • [emedicine.medscape.com] Entire Body System Anemia PATIENT CONCERNS: A patient known for hepatosplenomegaly with hyperferritinemia, anemia, and thrombocytopenia was admitted for Lewy body dementia and bullous pemphigoid.[symptoma.com]
  • A patient known for hepatosplenomegaly with hyperferritinemia, anemia, and thrombocytopenia was admitted for Lewy body dementia and bullous pemphigoid. Type 1 Gaucher disease.[ncbi.nlm.nih.gov]
  • General symptoms may begin in early life or adulthood and include skeletal disorders and bone lesions that may cause pain and fractures, enlarged spleen and liver, liver malfunction, anemia, and yellow spots in the eyes.[ninds.nih.gov]
Fatigue
  • Hematologic changes, bone pain, hepatomegaly, splenomegaly, and fatigue were the most recurrent signs and symptoms.[ncbi.nlm.nih.gov]
  • [symptoma.com] Fatigue Hematologic changes, bone pain, hepatomegaly, splenomegaly, and fatigue were the most recurrent signs and symptoms.[symptoma.com]
  • Symptoms include spleen and liver enlargement, bone problems and fatigue. Brain development is normal. Learn more about Gaucher disease type 1, which is treatable.[gaucherdisease.org]
  • People in this group usually bruise easily due to low blood platelets and experience fatigue due to anemia They also may have an enlarged liver and spleen. Many individuals with a mild form of the disorder may not show any symptoms.[ninds.nih.gov]
Weakness
  • However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype.[ncbi.nlm.nih.gov]
  • [ncbi.nlm.nih.gov] Weakness However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype.[symptoma.com]
  • The most commonly observed symptoms of hypersensitivity reactions were: headache, dizziness, low blood pressure, high blood pressure, nausea, tiredness/weakness, and fever.[vpriv.com]
  • Complications due to Gaucher Disease include: Blood-related abnormalities Bone disorders such as loss of bone minerals leading to weak bones and joints, bone-death Massive liver and spleen enlargement Severe neurological dysfunction, epileptic seizures[dovemed.com]
  • Skeletal weakness and bone disease may occur, leading to collapsed hips, shoulders, and spine. Inheritance Patterns Gaucher Disease Type I is an autosomal recessive disorder.[geneticdiseasefoundation.org]
Death in Infancy
  • This causes rapidly progressive neurovisceral storage disease and death during infancy. [ 3 ] Type 3 - juvenile or Norrbottnian form (chronic or subacute neuronopathic).[patient.info]
  • [tabletmag.com] Death in Infancy This causes rapidly progressive neurovisceral storage disease and death during infancy. [ 3 ] Type 3 - juvenile or Norrbottnian form (chronic or subacute neuronopathic).[symptoma.com]
  • Type 2 Gaucher disease causes rapidly progressive neurovisceral storage disease and death during infancy or during the first years of life.[emedicine.medscape.com]
Feeding Difficulties
  • [emedicine.com] Feeding Difficulties In addition, affected infants may experience difficulty swallowing (dysphagia), which may result in feeding difficulties ; abnormal positioning or bending of the neck (retroflexion); and failure to gain weight and[symptoma.com]
  • In addition, affected infants may experience difficulty swallowing (dysphagia), which may result in feeding difficulties; abnormal positioning or bending of the neck (retroflexion); and failure to gain weight and grow at the expected rate (failure to[rarediseases.org]
Stridor
  • This case was a girl diagnosed with type 2 Gaucher disease at 12months of age who presented with poor weight gain from infancy, stridor, hypertonia, hepatosplenomegaly, trismus and an eye movement disorder.[ncbi.nlm.nih.gov]
  • [ncbi.nlm.nih.gov] Failure to thrive, swallowing abnormalities, oculomotor apraxia, hepatosplenomegaly, and stridor due to laryngospasm are typical in infants with type 2 disease.[symptoma.com]
  • Failure to thrive, swallowing abnormalities, oculomotor apraxia, hepatosplenomegaly, and stridor due to laryngospasm are typical in infants with type 2 disease.[emedicine.medscape.com]
  • Acute neuronopathic Gaucher disease refers to the onset at less than one year of age of progressive stridor (constriction of the large tubes within the lungs, mainly the trachea), squint and swallowing difficulties.[web.archive.org]
  • Failure to thrive and stridor (due to laryngospasm) are also common. Rapid neurodegenerative course with extensive visceral involvement and death (usually caused by respiratory problems) within the first two years of life.[patient.info]
Abdominal Pain
  • pain, upper abdominal pain, back pain, and extremity pain.[ncbi.nlm.nih.gov]
  • The signs and symptoms of Type 1 can begin at any age, and usually include anemia, bruising, bleeding, abdominal pain (caused by an increase in spleen and liver size), bone pain, and growth problems.[pfizer.com]
  • [patient.info] Gastrointestinal Abdominal Pain pain, upper abdominal pain, back pain, and extremity pain.[symptoma.com]
  • I: (adult form) - chronic noneuronopathic type; - central nervous system is spared & disease is characterized by slowly progressive visceral and osseous involvement; - enlarged spleen may cause mechanical problems, including abdominal distention and abdominal[wheelessonline.com]
Failure to Thrive
  • Failure to thrive, swallowing abnormalities, oculomotor apraxia, hepatosplenomegaly, and stridor due to laryngospasm are typical in infants with type 2 disease.[emedicine.medscape.com]
  • [elelyso.com] Failure to Thrive Failure to thrive, swallowing abnormalities, oculomotor apraxia, hepatosplenomegaly, and stridor due to laryngospasm are typical in infants with type 2 disease.[symptoma.com]
  • Failure to thrive and stridor (due to laryngospasm) are also common. Rapid neurodegenerative course with extensive visceral involvement and death (usually caused by respiratory problems) within the first two years of life.[patient.info]
  • The symptoms include: Slow back-and-forth eye movement Not gaining weight or growing as expected, called "failure to thrive" High-pitched sound when breathing Seizures Brain damage, especially to the brain stem Enlarged liver or spleen Type 3.[webmd.com]
Dysphagia
  • [webmd.com] Dysphagia The various symptoms and the age when they are most likely to present are as follows: [4] Newborn Congenital ichthyosis Organomegaly Failure to thrive Brain stem dysfunction - Dysphagia, apnea, difficulty with secretions Hepatosplenomegaly[symptoma.com]
  • The various symptoms and the age when they are most likely to present are as follows: [4] Newborn Congenital ichthyosis Organomegaly Failure to thrive Brain stem dysfunction - Dysphagia, apnea, difficulty with secretions Hepatosplenomegaly Hematological[emedicine.medscape.com]
  • […] progressive condition characterized by hepatosplenomegaly and skeletal deformities; the neuronopathic forms are divided into infantile and juvenile forms; the infantile form presents at 4-5 months of age with anemia, loss of cognitive gains, neck retraction, dysphagia[icd10data.com]
  • They include: dysphagia, or difficulty swallowing problems with walking seizures These problems get worse and can ultimately be fatal.[medicalnewstoday.com]
Abdominal Distension
  • Headache, diarrhea, abdominal distension, and abdominal pain were also reported as related events in 3, 4, 1, and 1 placebo‐treated patients, respectively, during the 9‐month primary analysis period.[ncbi.nlm.nih.gov]
  • Distension Headache, diarrhea, abdominal distension, and abdominal pain were also reported as related events in 3, 4, 1, and 1 placebo‐treated patients, respectively, during the 9‐month primary analysis period.[symptoma.com]
Abdominal Mass
  • In this case presentation, a 13-year-oldadolescent with Gaucher disease on enzyme replacement treatment was presented, who was detected having an abdominal mass on a routine visit and diagnosed with partial torsion of a wandering spleen associated with[ncbi.nlm.nih.gov]
  • Mass In this case presentation, a 13-year-oldadolescent with Gaucher disease on enzyme replacement treatment was presented, who was detected having an abdominal mass on a routine visit and diagnosed with partial torsion of a wandering spleen associated[symptoma.com]
Bleeding Gums
  • As a result, Gaucher patients’ blood may not clot well, and they may experience excessive bruising, frequent nosebleeds, bleeding gums, and longer, heavier menstrual periods. 3: Low red blood cell count (anemia) Red blood cells are responsible for carrying[cerezyme.com]
  • [ncbi.nlm.nih.gov] Jaw & Teeth Bleeding Gums As a result, Gaucher patients’ blood may not clot well, and they may experience excessive bruising, frequent nosebleeds, bleeding gums, and longer, heavier menstrual periods. 3: Low red blood cell count (anemia[symptoma.com]
Hepatosplenomegaly
  • In order to avoid a misdiagnosis, a diagnostic algorithm for patients with hepatosplenomegaly combined with cytopenia is suggested.[ncbi.nlm.nih.gov]
  • [ncbi.nlm.nih.gov] Less common signs of the disease are hepatosplenomegaly, ichthyosis, arthrogryposis and facial dysmorphy.[symptoma.com]
Hepatomegaly
  • After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively.[ncbi.nlm.nih.gov]
  • Radiographically, hepatomegaly and splenomegaly respond more rapidly than skeletal changes. Glucosylceramide synthase inhibitors are available for patients with Type 1 GD who cannot receive enzyme replacement therapy 8.[radiopaedia.org]
  • [ncbi.nlm.nih.gov] Hepatomegaly After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively.[symptoma.com]
Jaundice
  • Investigations General assessment FBC and differential (assess the degree of pancytopenia); LFTs (minor elevations of liver enzymes are common but jaundice is a poor prognostic indicator).[patient.info]
  • [emedicine.medscape.com] Jaundice Investigations General assessment FBC and differential (assess the degree of pancytopenia); LFTs (minor elevations of liver enzymes are common but jaundice is a poor prognostic indicator).[symptoma.com]
  • The gastrointestinal features include hepatosplenomegaly, jaundice , hepatic (liver) failure, and ascites (fluid in the abdomen).[medicinenet.com]
Corneal Opacity
  • Although corneal opacities are virtually unknown in GD, except in the D409H homozygous cardiovascular subtype, this patient had marked corneal stromal abnormalities.[ncbi.nlm.nih.gov]
  • [emedicine.com] Corneal Opacity Although corneal opacities are virtually unknown in GD, except in the D409H homozygous cardiovascular subtype, this patient had marked corneal stromal abnormalities.[symptoma.com]
  • One rare subgroup of patients with type 3 Gaucher disease present with oculomotor findings, calcifications of the mitral and aortic valves, and corneal opacities. The phenotype is associated with homozygosity for the D409H mutant allele.[emedicine.medscape.com]
  • Clinical manifestations vary by subtype and include progressive dementia and ataxia (IIIa), bone and visceral involvement (IIIb), and supranuclear palsies with corneal opacities (IIIc). Patients who survive to adolescence may live for many years.[merckmanuals.com]
Strabismus
  • Patients with this type may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly.[emedicine.medscape.com]
  • [medicinenet.com] Eyes Strabismus Patients with this type may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly.[symptoma.com]
  • Type 2 Gaucher's disease Presents in infancy with increased tone, strabismus, and organomegaly. Failure to thrive and stridor (due to laryngospasm) are also common.[patient.info]
  • Patients with type 2 disease may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly.[emedicine.com]
Bone Pain
  • Clinically apparent bony involvement, which occurs in more than 20% of patients with Gaucher disease, can present as bone pain or pathologic fractures.[emedicine.medscape.com]
  • Medicines may be given to: Replace the missing GBA (enzyme replacement therapy) to help reduce spleen size, bone pain, and improve thrombocytopenia. Limit production of fatty chemicals that build up in the body.[nlm.nih.gov]
  • [rarediseases.org] Musculoskeletal Bone Pain Clinically apparent bony involvement, which occurs in more than 20% of patients with Gaucher disease, can present as bone pain or pathologic fractures.[symptoma.com]
  • It is usually diagnosed in the first or second decade of life with the appearance of bone pains, splenomegaly and thrombocytopenia, but the disease may be diagnosed at any age between 1 and 73 years.[ncbi.nlm.nih.gov]
Osteoporosis
  • Type 1 Gaucher disease (GD1) is characterized by thrombocytopenia, anemia, an enlarged spleen, and liver as well as bone complications (Erlenmeyer flask deformity, osteoporosis, lytic lesions, pathological and vertebral fractures, bone infarcts, and avascular[ncbi.nlm.nih.gov]
  • [ncbi.nlm.nih.gov] Frequent misdiagnoses include leukemia, lymphoma, rheumatoid arthritis and osteoporosis.[symptoma.com]
  • Frequent misdiagnoses include leukemia, lymphoma, rheumatoid arthritis and osteoporosis. Clinical features are extremely variable in each patient, and even within a family various members can exhibit a very different clinical problems and course.[massgeneral.org]
Arthritis
  • Frequent misdiagnoses include leukemia, lymphoma, rheumatoid arthritis and osteoporosis.[symptoma.com]
  • Frequent misdiagnoses include leukemia, lymphoma, rheumatoid arthritis and osteoporosis. Clinical features are extremely variable in each patient, and even within a family various members can exhibit a very different clinical problems and course.[massgeneral.org]
  • […] 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[ghr.nlm.nih.gov]
  • (hepatomegaly) and enlarged spleen (splenomegaly) Decreased blood cell count causing anemia Individuals with anemia may have fatigue, low energy, and decreased exercise tolerance Decreased platelet count can cause easy bruising Bone and joint pain, arthritis[dovemed.com]
Back Pain
  • pain, and extremity pain.[ncbi.nlm.nih.gov]
  • [patient.info] Gastrointestinal Abdominal Pain pain, upper abdominal pain, back pain, and extremity pain.[symptoma.com]
  • The most common adverse reactions for ELELYSO are itching, flushing, headache, joint pain, pain in extremity, abdominal pain, vomiting, diarrhea, fatigue, back pain, dizziness, nausea, and rash.[elelyso.com]
  • The most commonly reported side effects during clinical studies (in 10% of patients) were hypersensitivity reactions, headache, dizziness, abdominal pain, nausea, back pain, joint pain, increased time it takes for blood to clot, tiredness/weakness, and[vpriv.com]
  • pain 3 months Chronic back pain greater than 3 months duration Chronic coccyx pain 3 months Chronic pain in coccyx for more than 3 months (finding) Fabry disease Fabrys disease Fabry's disease Ganglioside sialidase deficiency Gaucher disease Gauchers[icd9data.com]
Arthralgia
  • […] following 10 adverse events noted in the eliglustat US Prescribing Information (USPI) and EU Summary of Product Characteristics (SmPC) were evaluated with regard to frequency, drug-relatedness, severity, seriousness, duration, and timing of onset: headache, arthralgia[ncbi.nlm.nih.gov]
  • arthralgia is common [ncbi.nlm.nih.gov] Toxicity The most common toxic reaction seen was infusion reactions such as urticaria, arthralgia, headache, and chest pain due to IV administration.[symptoma.com]
  • Toxicity The most common toxic reaction seen was infusion reactions such as urticaria, arthralgia, headache, and chest pain due to IV administration.[drugbank.ca]
  • Headache, nasopharyngitis, traumatic injury, arthralgia, cough, pyrexia, dizziness, nasal congestion, influenza, bone pain and prolonged activated partial thromboplastin time (aPTT) were the most common.[doi.org]
Epistaxis
  • Epistaxis and ecchymoses resulting from thrombocytopenia are common. X-rays show flaring of the ends of the long bones (Erlenmeyer flask deformity) and cortical thinning.[merckmanuals.com]
  • [drugbank.ca] Face, Head & Neck Epistaxis Epistaxis and ecchymoses resulting from thrombocytopenia are common. X-rays show flaring of the ends of the long bones (Erlenmeyer flask deformity) and cortical thinning.[symptoma.com]
Seizure
  • T y pe 2 Gaucher disease (acute infantile neuropathic Gaucher disease) symptoms usually begin by 3 months of age and includes extensive brain damage, seizures, spasticity, poor ability to suck and swallow, and enlarged liver and spleen.[ninds.nih.gov]
  • Patients with this type may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly.[emedicine.medscape.com]
  • [merckmanuals.com] Neurologic Seizure Patients with this type may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly.[symptoma.com]
  • Type 2 GD patients suffer significant progressive neurological impairment, including spasticity, opisthotonus, seizure, and apnea. The recently developed enzyme replacement therapy (ERT) has shown therapeutic benefit for GD.[ncbi.nlm.nih.gov]
Peripheral Neuropathy
  • Comorbidities for peripheral neuropathy were excluded.[ncbi.nlm.nih.gov]
  • A study published in the Orphanet Journal of Rare Diseases confirmed the role played by peripheral neuropathy in Gaucher pain.[raredr.com]
  • [ncbi.nlm.nih.gov] Peripheral Neuropathy Comorbidities for peripheral neuropathy were excluded. [ncbi.nlm.nih.gov] A study published in the Orphanet Journal of Rare Diseases confirmed the role played by peripheral neuropathy in Gaucher pain.[symptoma.com]
  • Tremor and peripheral neuropathy are infrequent and non-serious events in Gaucher type 1 patients treated with eliglustat [abstract]. Mol Genet Metab. 2015;114(2):S69–70. Google Scholar 24. Hughes D, Cappellini MD, Berger M, et al.[doi.org]
Opisthotonus
  • Type 2 GD patients suffer significant progressive neurological impairment, including spasticity, opisthotonus, seizure, and apnea. The recently developed enzyme replacement therapy (ERT) has shown therapeutic benefit for GD.[ncbi.nlm.nih.gov]
  • [doi.org] Opisthotonus Type 2 GD patients suffer significant progressive neurological impairment, including spasticity, opisthotonus, seizure, and apnea. The recently developed enzyme replacement therapy (ERT) has shown therapeutic benefit for GD.[symptoma.com]
Myoclonic Jerking
  • Before the introduction of miglustat, this patient experienced frequent multifocal myoclonic jerks (up to 50 generalized seizures per day) as well as severe dystonia in his arms and legs, which confined him to a wheelchair.[jmedicalcasereports.biomedcentral.com]
Polyneuropathy
  • Among them, 10.7% were diagnosed with sensory motor axonal polyneuropathy at baseline using standardized electrophysiological assessment. Six new cases of polyneuropathy were revealed during two-years monitoring (2.9 per 100 person-years).[content.sciendo.com]

Workup

Although the diagnosis can't be made solely on physical signs, a clinical suspicion toward this condition should be made in patients where other causes have been excluded, such as lymphomas and leukemias, as well as other lysosomal storage diseases that have a similar clinical presentation [3]. Workup starts with a complete blood count (CBC) that almost always reveals anemia and thrombocytopenia, while ultrasonography or computed tomography (CT) can confirm hepatosplenomegaly. The first major diagnostic tool is bone marrow biopsy, which will show the presence of Gaucher cells in macrophages that contain a granullar blue-to-gray cytoplasm and a characteristic wrinkled-paper appearance [3]. Periodic acid-Schiff staining is positive in the setting of GD, whereas special immunohistochemical staining (CD68) is positive as well [3]. Once Gaucher cells have been identified, further confirmation can be obtained by performing genetic testing, to determine the exact mutations that are responsible for this disease [4].

Decreased Platelet Count
  • Platelet Count [britannica.com] Serum Decreased Platelet Count [en.wikipedia.org] Serum Decreased Platelet Count Decreased platelet counts (thrombocytopenia) as well as low hemoglobin (anemia) and decreased white blood cell counts (leukopenia) result[symptoma.com]
  • Decreased platelet counts (thrombocytopenia) as well as low hemoglobin (anemia) and decreased white blood cell counts (leukopenia) result in easy bruisability and hence black-and-blue marks (ecchymoses); easy bleeding--for example, after dental interventions[scientificamerican.com]
  • platelet count can cause easy bruising Bone and joint pain, arthritis of joints, weakening of the bones resulting in easy fractures Lung disease can cause breathing difficulties In Type I Gaucher Disease, there are no symptoms related to the central[dovemed.com]
Enlargement of the Spleen
  • General symptoms may begin in early life or adulthood and include skeletal disorders and bone lesions that may cause pain and fractures, enlarged spleen and liver, liver malfunction, anemia, and yellow spots in the eyes.[ninds.nih.gov]
  • Gau·cher disease \ (ˌ)gō-ˈshā- \ variants: or Gaucher's disease \ (ˌ)gō-ˈshāz- \ Definition of Gaucher disease : a rare hereditary disorder of lipid metabolism caused by an enzyme deficiency and characterized by enlargement of the spleen and liver, bone[merriam-webster.com]
  • Mutations in GBA lead to the accumulation of glycosylceramide in the lysosome causing an enlargement of the spleen and the liver and skeletal deformations. This disease is called Gaucher Disease.[ncbi.nlm.nih.gov]
  • Ultrasound Enlargement of the Spleen […] and liver, bone [merriam-webster.com] Ultrasound Enlargement of the Spleen Mutations in GBA lead to the accumulation of glycosylceramide in the lysosome causing an enlargement of the spleen and the liver and skeletal[symptoma.com]
  • Symptoms of the disease may include enlargement of the spleen and liver (a big belly or abdomen), anemia, thrombocytopenia (low platelet counts), bone pain, and bone fragility. Gaucher disease. [Internet]. Medline Plus [updated January 12, 2016].[thinkgenetic.com]
Enlargement of the Liver
  • Type 1 Gaucher disease (GD1) is characterized by thrombocytopenia, anemia, an enlarged spleen, and liver as well as bone complications (Erlenmeyer flask deformity, osteoporosis, lytic lesions, pathological and vertebral fractures, bone infarcts, and avascular[ncbi.nlm.nih.gov]
  • [britannica.com] Enlargement of the Liver Type 1 Gaucher disease (GD1) is characterized by thrombocytopenia, anemia, an enlarged spleen, and liver as well as bone complications (Erlenmeyer flask deformity, osteoporosis, lytic lesions, pathological and[symptoma.com]
  • General symptoms may begin in early life or adulthood and include skeletal disorders and bone lesions that may cause pain and fractures, enlarged spleen and liver, liver malfunction, anemia, and yellow spots in the eyes.[ninds.nih.gov]
  • This accumulation causes cells to form what is known as "Gaucher cells" which displace healthy cells in bone marrow, cause an enlargement of the liver and spleen, organ dysfunction, and deterioration of the skeleton.[stlouischildrens.org]
  • It results in bone fragility, neurological disturbance, anaemia, and enlargement of the liver and spleen. ‘Gene therapy is feasible, and some preliminary studies have already been carried out in Gaucher's disease.’[en.oxforddictionaries.com]
Bone Marrow Gaucher Cells
  • The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, the spleen and the bone marrow (Gaucher cells).[orpha.net]
  • Marrow Gaucher Cells The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, the spleen and the bone marrow ( Gaucher cells[symptoma.com]

Treatment

GD is the first lysosomal storage disease that is treated by enzyme replacement therapy. Imiglucerase and velaglucerase are two compounds that are administered as injections and are true analogs of human glucocerebrosidase [7]. Their administration has shown almost complete reversal of symptoms within months of treatment [14]. Through early and regular administration, enzyme-replacement therapy has shown marked improvements in survival and overall quality of life, but since imiglucerase does not cross the blood-brain barrier [3], types 2 and 3 are not as effectively treated as type 1. Equally effective is miglustat, a drug that is given orally and inhibits formation of the compound that accumulates inside lysosomes, thus contributing to the same effect having almost equal efficacy.

Prognosis

The prognosis of patients suffering from GD depends on two factors: the clinical subtype and time of treatment initiation. Type 2 clinical presentation carries a very poor prognosis, as severe neurological symptoms are universally fatal by the age of 5 [1]. On the other hand, types 1 and 3 carry a much better prognosis. Type 1 has an adult onset of non-neurological symptoms and since the discovery and use of enzyme replacement therapy, life expectancy is close to near-normal [12], but an early recognition of the disease and prompt initiation of therapy is detrimental [3]. Adult forms (type I) have shown to achieve normal life expectancy in many studies. Although type 3 is associated with a relatively milder clinical course in regard to type 2, the prognosis is not as good as in type 1 patients.

Etiology

The cause of GD is deficiency of glucocerebrosidase, an enzyme that should normally break down glycolipids, primarily glucocerebroside (also known as glycoceramide) [8]. Enzyme deficiency occurs as a result of gene mutations that code the glucocerebrosidase enzyme, located on chromosome 1q21 and the mode of inheritance is shown to be autosomal recessive. More than 200 mutations have been documented so far and it is shown that different mutations lead to different clinical symptoms [3].

Epidemiology

Estimated incidence rates suggest that GD is one of the most common lysosomal storage diseases, occurring in approximately 1 in 57,000 live births [5]. Various studies have shown a significantly higher incidence rate in Ashkenazi Jews that reaches up to 1 in 1,000 live births, as up to 7% of all Asheknazi Jews are shown to be heterozygotes for GD [3]. Having in mind the autosomal recessive pattern of inheritance, genders are equally affected, but age of onset significantly varies on the clinical subtype. Type 1 appears in adulthood, type 2 appears in early infancy, while the onset of type 3 is most frequently observed during the juvenile period [3].

Sex distribution
Age distribution

Pathophysiology

The hallmark of GD is deficiency of glucocerebrosidase, the enzyme responsible for degradation of glucocerebroside, a membrane glycolipid that is present on virtually all cells in the body. Glucocerebroside (also known as glucosylceramide) is an important constituent of the cell membrane [9], and due to various mutations that have been identified, enzyme deficiency leads to accumulation of glucocerebroside inside lysosomes, primarily in macrophages and monocytes [10]. As a result, the primary and secondary lymphoid organs are affected, including the bone marrow, spleen, liver and kidneys, while neuroinflammation and degeneration have been hypothesized as main mechanisms of neuronal injury [11]. Animal models show that activation of numerous cytokines, such as interleukin 1 (IL-1), IL-6, tumor necrosis α (TNF-α) and many other lead to a chronic inflammatory response in the presence of macrophages containing Gaucher cells [11].

Prevention

Wide-scale screening, especially in Ashkenazi Jews, but in families with confirmed GD patients can be a helpful measure in determining the risk for further development of GD. In such circumstances, genetic counseling may be conducted, but other than screening, preventive measures currently do not exist, although much has been discovered in terms of pathophysiology and treatment.

Summary

Gaucher disease (GD) is a genetic disorder in which deficiency of glucocerebrosidase, an enzyme that is responsible for degradation of a glycolipid-glucocerebroside, is transferred by autosomal recessive pattern of inheritance [1]. It is the most common and earliest lysosomal storage disease discovered, dating back to the end of the 19th century [2], but the exact cause was determined at the end of the 20th century, when first gene mutations were identified [3]. Numerous mutations in the glucocerebroside gene, whose location is on chromosome 1q21, have been discovered, with more than 200 being described so far. As a result of enzyme deficiency, accumulation of glucocerebroside in cells occurs, primarily in monocytes and macrophages [4]. Although the exact mechanism of intracellular damage is unclear, macrophages that have stored glucocerebroside (Gaucher cells) accumulate in the liver, spleen, kidneys and bone marrow, organs that are principally affected by this condition [4]. Incidence rates suggest that this disorder appears in approximately 1 in 57,000 live births [5], but a significant ethnic predilection in Ashkenazi Jews has been established. Almost 7% of people in this ethnic group are heterozygous for GD and the estimated incidence rate is estimated to be 1 in 1000 [5]. There are three distinct clinical subtypes of GD:

The diagnosis can often be delayed due to the nonspecific clinical presentation of patients. Laboratory studies that show anemia and other hematological abnormalities, together with marked hepatosplenomegaly will usually indicate a bone marrow biopsy, which will show the presence of enlarged Gaucher cells that have a blue-to-gray cytoplasm that is filled with granules or fibrills [3]. Genetic testing, when possible, can be performed, to assess the presence of gene mutations. Fortunately, GD is one of the first diseases in which enzyme replacement therapy has shown marked success and various forms exist. Alglucerase and imiglucerase, analogs of human glucocerebrosidase, are administered as injections and are well tolerated [7], while Miglustat is an oral drug that serves as an inhibitor of glucocerebroside formation [4]. The prognosis mainly depends on clinical presentation, as type II is usually fatal before 5 years of age. Life expectancy in patients suffering from type 1 or type 3, on the other hand, may be significantly prolonged if therapy is started early on. For this reason, GD must be diagnosed in early stages so that treatment can result in better outcomes.

Patient Information

Gaucher disease (GD) arises from deficiency of an enzyme, glucocerebrosidase, and subsequent deposition of substances (cell membrane constituents known as glucocerebrosides or glycoceramides) inside small organelles called lysosomes which would otherwise be degraded. Together with other disease, such as Tay-Sachs and Niemann-Pick disease, GD belongs to the group of lysosomal storage diseases. Enzyme deficiency stems from mutations in genes that code for this enzyme and these gene alterations are transmitted by an autosomal recessive pattern of inheritance. Normally, a person carries two genes for this enzyme, and if a single gene is transmitted from one parent, the disease will not develop, but if both parents transmit their mutated gene, it will result in GD. Because of enzyme deficiency, substances accumulate inside various cells in the body, but mainly in white blood cells that travels to various organs where they exert their effects on tissues. Although the exact mechanism of disease is not known, chronic inflammation and degeneration of nervous tissue as a result of defective white blood cell functioning is the current theory. It is established that GD occurs in approximately 1 child per 57,000 births and there are three main clinical subtypes. Type 1 is by far the most common, representing between 95-99% of all cases. Symptoms appear in adulthood and include enlarged liver and spleen, anemia, low thrombocyte count and skeletal abnormalities; Type 2 is the most severe form that develops in early life (symptoms appear at < 2 years of age) and involves severe neurological deficits - convulsions, mental disability and is fatal within a few years; Type 3 also involves the nervous system, but in a much milder fashion and is primarily seen in childhood and adolescence. To make the diagnosis, blood tests and bone marrow biopsy are necessary, which will show the presence of defective macrophages - Gaucher cells in bone marrow. Once they are observed, genetic testing may be used to identify the specific mutations that are responsible for the disease. Luckily, GD is one of the first lysosomal storage diseases that are treatable and drugs that are used are either supplements of the deficient enzyme or compounds that reduce production of content that accumulates inside cells. But treatment can be most effective when it is administered in earlier stages of the disease, as damage caused by inflammation and other processes may be permanent if not stopped on time. Early use of therapy has significantly prolonged life expectancy in these patients and is estimated to be as normal for type 1, but type 2 is universally fatal by the age of 5 despite treatment. The outcome of patients with type 3 severely depends on the severity of symptoms and onset of therapy.

References

Article

  1. Moyses C. Substrate reduction therapy: clinical evaluation in type 1 Gaucher disease. Philos Trans R Soc Lond B Biol Sci. 2003;358:955.
  2. Mehta A, Beck M, Sunder-Plassmann G, editors. History of lysosomal storage diseases: an overview. In Fabry Disease: Perspectives from 5 Years of FOS. Oxford: Oxford PharmaGenesis; 2006.
  3. Chen M, Wang J. Gaucher disease: review of the literature. Arch Pathol Lab Med. 2008;132(5):851-853.
  4. Cox TM, Aerts JM, Andria G, et al. The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement. J Inherit Metab Dis. 2003;26:513.
  5. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999;281:249–254.
  6. Packman W, Crosbie TW, Behnken M, et al. Living with Gaucher disease: Emotional health, psychosocial needs and concerns of individuals with Gaucher disease. Am J Med Genet A. 2010;152A:2002.
  7. Zimran A, Altarescu G, Philips M, et al. Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood. 2010;115:4651.
  8. Beutler E, Grabowski GA. Gaucher disease. In: Metabolic and molecular bases of inherited disease, Scriver CR, Beaudet AL, Sly WS, Valle D (Eds), McGraw-Hill, New York; 2001. p.3635.
  9. Messner MC, Cabot MC. Glucosylceramide in humans. Adv Exp Med Biol 2010;688:156.
  10. Cox TM, Aerts JM, Belmatoug N, et al. Management of non-neuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring. J Inherit Metab Dis. 2008;31:319.
  11. Vitner EB, Farfel-Becker T, Eilam R, Biton I, Futerman AH. Contribution of brain inflammation to neuronal cell death in neuronopathic forms of Gaucher's disease. Brain. 2012;135(6):1724-1735.
  12. Weinreb NJ, Deegan P, Kacena KA et al. Life expectancy in Gaucher disease type 1. Am J Hematol. 2008;83(12):896-900.
  13. Pastores GM, Weinreb NJ, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol. 2004;41:4.
  14. Baldellou A, Andria G, Campbell PE, et al. Paediatric non-neuronopathic Gaucher disease: recommendations for treatment and monitoring. Eur J Pediatr. 2004;163:67.

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Last updated: 2020-02-08 22:17