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

• Type 1 - This subtype comprises between 95-99% of all clinical presentations encountered in medical practice [1]. The main clinical features include massive hepatosplenomegaly, anemia, thrombocytopenia and skeletal abnormalities such as avascular necrosisis and osteopenia. Growth retardation, pulmonary disease, bleeding tendencies and hypermetabolic states may also be reported in these patients [13].
• Type 2 - The most severe form of GD is characterized by the onset of convulsions, dementia, mental disability, myoclonus and muscle apraxia [3]. Symptoms are rapidly progressive and the majority of children die up to 5 years of age despite treatment [3].
• Type 3 - Usually, this form is most common in juvenile period and presents with similar but less severe complaints compared to type 2.

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

• Splenomegaly

  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]

  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]

  […] type IIIa Gaucher disease, type IIIb Gaucher disease, type IIIc Gaucher disease, Norrbottnian type Gaucher disease, perinatal lethal Gaucher disease, collodion type Gaucher disease, juvenile and adult, cerebral GD cerebroside lipidosis syndrome Gaucher splenomegaly [flybase.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

  […] inheritance pattern autosomal recessive classification Type 1 ( B-glucocerebrosidase deficency) is most common Type 2 Type 3 (with CNS involvement) Classification Classification Type Clinical Features Prognosis Type 1 (Adult Type) • Easy bruising • Anemia [orthobullets.com]

  [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]

  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]

  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]

• 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]

• Splenectomy

  Only 1 patient required conversion to open surgery because of multiple adhesions from a previous partial splenectomy. [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. [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]

• Developmental Delay

  The inferred diagnoses for the studied population were: Risk for bleeding; Fatigue; Chronic pain and Acute pain; Impaired physical mobility; Imbalanced nutrition: less than body requirements; and Risk for Developmental Delay. [ncbi.nlm.nih.gov]

  […] non-CNS effects respond well to enzyme replacement therapy Presentation Symptoms (will depend on the type of Gaucher's disease) Systemic Manifestations fatigue (anemia) prolonged bleeding (thrombocytopenia) fever, chills, sweats (infection) seizure, developmental [orthobullets.com]

  delays In type II, rigidity and seizures may appear within the first few months of life. [uvahealth.com]

  In addition to organomegaly and bony involvement, neurological involvement is present, including developmental delay and abnormal neurological findings - eg, increased tendon reflexes. [patient.info]

• 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]

  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, swallowing abnormalities, oculomotor apraxia, hepatosplenomegaly, and stridor due to laryngospasm are typical in infants with type 2 disease. [emedicine.medscape.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]

• Common Cold

  Chronic Adenitis What is the most common cause of chronic adenitis, persisting longer than 21 days, in children, and how is the diagnosis made? Cervical Adenitis Cervical Adenitis. Description. [catsclem.nl]

• Abdominal Pain

  pain, upper abdominal pain, back 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 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]

  […] distention and abdominal pain as well as shortness of breadth, as well as causing pan cytopenia; - splenectomy may be performed for thrombocytopenia; - bone pain is a common complaint, which often resolves after 1-2 days; - bone pain may also be due [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]

  Symptoms include enlarged spleen and liver, which are often present at birth; liver malfunction; bone deformities, pain or crises; severe neurologic complications; and failure to thrive. [idph.state.il.us]

  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 [icd9data.com]

  They include: dysphagia, or difficulty swallowing problems with walking seizures These problems get worse and can ultimately be fatal. [medicalnewstoday.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 [icd9data.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, early satiety, new splenic infarction  Eliminate hypersplenism *Please note regular assessments will be conducted. 23. [slideshare.net]

  […] with [ncbi.nlm.nih.gov] 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. [symptoma.com]

  Symptomatic splenomegaly with pain, early satiety and abdominal distension or cytopenias due to splenic pooling may be the presenting features of GD. [onlinelibrary.wiley.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]

• Trismus

  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]

  […] and grow at the expected rate (failure to [rarediseases.org] Respiratoric 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 [symptoma.com]

• Hepatomegaly

  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]

  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]

  [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

  The gastrointestinal features include hepatosplenomegaly, jaundice, hepatic (liver) failure, and ascites (fluid in the abdomen). [medicinenet.com]

  The disorder can result in pain, fatigue, jaundice, bone damage, anaemia and even death. Gaucher disease is an autosomal recessive disorder. [brainfoundation.org.au]

  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]

  Some of the symptoms are listed below: Liver Hepatomegaly – large liver Enlarged abdomen Cirrhosis – scarred liver Abnormal liver tests, jaundice & other signs of liver disease Predisposition to gall stones Often no symptoms – sometimes abdominal pain [cuh.nhs.uk]

  [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]

• Liver Fibrosis

  Infants experience profound growth failure, liver fibrosis, and cirrhosis, with a median age of death at 3.7 months. [aetna.com]

• Hydrops Fetalis

  The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis, in utero fetal demise and neonatal distress. [ncbi.nlm.nih.gov]

  A severe neonatal form can present in utero or perinatally with hydrops fetalis, congenital ichthyosis, or both. Often, there is a maternal history of miscarriages without an established cause. [emedicine.medscape.com]

  fetalis), dry skin (ichthyosis) enlarged spleen and liver, distinct facial features; and severe neurological problems. [physio-pedia.com]

  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 [ghr.nlm.nih.gov]

  Signs of this forminclude: Swelling caused by fluid build-up before birth (hydrops fetalis) Dry, scaly skin (ichthyosis) or other skin abnormalities Swollen stomach Distinctive facial features Severe neurological problems Gaucher disease, cardiovascular [babysfirsttest.org]

• Bone Pain

  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]

  Supportive management for bone pains or bone crises is frequently required and orthopaedic surgery may be needed for pathological fractures or osteonecrosis. [patient.info]

  Other treatments include: Medicines for pain Surgery for bone and joint problems, or to remove the spleen Blood transfusions How well a person does depends on their subtype of the disease. [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]

• Osteopenia

  Generalized rarefaction of bone (osteopenia) was present in 83.8%, and well-defined radiolucent lesions in 40.5%. [ncbi.nlm.nih.gov]

  Dual-energy X-ray absorptiometry (DEXA) scanning: evaluation of osteopenia. [patient.info]

  In patients with symptomatic bone disease, lytic lesions can develop in the long bones, ribs, and pelvis, and osteosclerosis or osteopenia may be evident at an early age. [emedicine.medscape.com]

  Osteopenia/Osteoporosis Both osteopenia and osteoporosis refer to abnormal reduction of bone mass and density. Both cortical and medullary bone are affected. [oatext.com]

• 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]

  Disease manifestations include hepatosplenomegaly, thrombocytopenia, anemia, osteopenia/osteoporosis with pathologic fractures and osteonecrosis, and, less commonly, pulmonary infiltration. [accessmedicine.mhmedical.com]

  […] nodes, bone marrow, GI and GU tracts; Kupffer cells in liver; osteoclasts in bone; microglia in CNS; and alveolar macrophages in lungs ( Arch Pathol Lab Med 2008;132:851 ) Clinical features Three subtypes; all may have hepatosplenomegaly, hypersplenism, osteoporosis [pathologyoutlines.com]

• 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]

  Condition does not occur in the specified paediatric subset Ilaris (canakinumab) Yes 2 PW Juvenile idiopathic arthritis (birth to < 24 months) Condition does not occur in the specified paediatric subset and no significant therapeutic benefit June 2015 [ojrd.biomedcentral.com]

  […] 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]

• Back Pain

  upper abdominal pain, back pain, and extremity pain. [ncbi.nlm.nih.gov]

  arthritis [symptoma.com] Back Pain pain, and extremity pain. [symptoma.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]

  Stability was defined by the following pre-specified thresholds of change: hemoglobin level Side Effects Adverse effects associated with the use of Cerdelga may include, but are not limited to, the following: fatigue headache nausea diarrhea back pain [centerwatch.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]

• Strabismus

  The first signs are oculomotor paralysis or bilateral fixed strabismus associated with bulbar signs, in particular severe swallowing difficulties, progressive spasticity and dystonic movements. [orpha.net]

  [medicinenet.com] Eyes Strabismus Patients with this type may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly. [symptoma.com]

  Patients with this type may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly. [emedicine.medscape.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]

  Other findings may include rapid head thrusts, bilateral fixed strabismus, and/or neck muscle hypertonia, limb rigidity, and seizures. [icahn.mssm.edu]

• 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]

  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. [msdmanuals.com]

• 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. [msdmanuals.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]

  Within a few years, all of participants with the disease had to restart the original enzyme replacement therapy schedule because of a symptomatic setback of the disease.[15] Effects of Enzyme Replacement Therapy[15] Description[15] Symptomatic Decreased epistaxis [physio-pedia.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]

  [merckmanuals.com] Neurologic Seizure Patients with this type may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly. [symptoma.com]

  Here we present a 36 year old male patient presenting with hip pain showing bilateral avascular necrosis of femoral head with massive splenomegaly and on evaluation, showed mental retardation, seizures, bilateral vertical and horizontal gaze palsies and [ncbi.nlm.nih.gov]

• Neurologic Manifestation

  The glycosphingolipidosis, Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β-glucocerebrosidase, with subsequent accumulation of β-glucocerebroside, its upstream substrates, and the non-acylated [ncbi.nlm.nih.gov]

• Headache

  [ncbi.nlm.nih.gov] The most commonly observed symptoms of hypersensitivity reactions were: headache, dizziness, low blood pressure, high blood pressure, nausea, tiredness/ weakness, and fever. [symptoma.com]

  The 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 [ncbi.nlm.nih.gov]

  The most commonly observed symptoms of hypersensitivity reactions were: headache, dizziness, low blood pressure, high blood pressure, nausea, tiredness/weakness, and fever. [vpriv.com]

  This includes: diminished ataxia (unsteadiness); IQ increased markedly; disappearance of severe headaches and epilepsy stayed under control despite withdrawal of anti-epileptic medication in one patient. [web.archive.org]

• Myoclonus

  The phenotype was unusually severe with congenital ichthyosis, hepatosplenomegaly, muscular hypotonia, myoclonus and respiratory failure. [ncbi.nlm.nih.gov]

  Type 3a presents with progressive neurologic involvement dominated by dementia and myoclonus (involuntary muscle twitching). Type 3b presents with aggressive skeletal and visceral symptoms. [themedicalbiochemistrypage.org]

• Bradykinesia

  Initially, 17 subjects were identified with Gaucher disease and l -DOPA refractory parkinsonian manifestations that included tremor, bradykinesia, rigidity, and often cognitive decline. 1 Several of the subjects had Lewy bodies and gliosis specifically [jmg.bmj.com]

  Additional noted trends were that subjects carrying mutations presented an average of 4 years earlier, were more likely to have a family history of PD, and had less bradykinesia and rest tremor and more cognitive changes described [ 50 ]. [doi.org]

  Additional noted trends were that subjects carrying mutations presented an average of 4 years earlier, were more likely to have a family history of PD, and had less bradykinesia and rest tremor and more cognitive changes described [50]. [karger.com]

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].

• Atelectasis

  Ingeklapte long About Atelectasis - Adam.Com Atelectasis (collapse of lung) - Merck Manual Atelectasis [pathol image] - Semmelweis U. [catsclem.nl]

• 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]

  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]

  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]

  As indicated, enlargement of the liver is characteristic in all Gaucher disease patients. In severe cases the liver can fill the entire abdomen. [themedicalbiochemistrypage.org]

  Lipoidosis, sphingomyelin: Also called Niemann- Pick disease, this is a disorder of the metabolism of a lipid (fat) called sphingomyelin that usually causes the progressive development of enlargement of the liver and spleen (hepatosplenomegaly), "swollen [medicinenet.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]

  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]

  Gaucher disease leads to an enlarged liver and spleen and a brownish pigmentation of the skin. Accumulations of glucocerebrosides in the eyes cause yellow spots called pingueculae to appear. [merckmanuals.com]

  Other signs include: Poor development Seizures Spasticity (jerking movements) Poor ability to suck and swallow Enlarged liver and spleen Due to their shortened lifespan, babies with Gaucher disease type 2 do not survive long enough to develop other typical [gaucherdisease.org]

• Cytopenia

  In order to avoid a misdiagnosis, a diagnostic algorithm for patients with hepatosplenomegaly combined with cytopenia is suggested. [ncbi.nlm.nih.gov]

  GD type 1 (90% of cases) is the chronic and non-neurological form associated with organomegaly (spleen, liver), bone anomalies (pain, osteonecrosis, pathological fractures) and cytopenia. [orpha.net]

• 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]

  […] low energy, and decreased exercise tolerance Decreased 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 [dovemed.com]

• Microcytosis

  The demonstrable cardiac, renal, or pulmonary symptoms are usually absent.1–3,5 LABORATORY FINDINGS AND MORPHOLOGIC FEATURES The peripheral blood usually shows a moderate to marked anisopoikilocytosis, mild microcytosis, hypochromia, and moderate thrombocytopenia [archivesofpathology.org]

• Hepatocellular Carcinoma

  Gaucher's disease has been correlated with cases of myeloma, leukemia, glioblastoma, lung cancer, and hepatocellular carcinoma, although the reasons for the correlation are currently being debated. [ncbi.nlm.nih.gov]

  Arthur Zimmermann, Etiology and Pathogenesis of Hepatocellular Carcinoma: Hepatocellular Carcinoma Associated with Inborn Errors of Metabolism and Hepatobiliary Malformations, Tumors and Tumor-Like Lesions of the Hepatobiliary Tract, 10.1007/978-3-319 [doi.org]

• 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]

  […] in the cells of the reticuloendothelial system of the liver, the spleen and the bone marrow ( Gaucher cells ). [symptoma.com]

• Liver Biopsy

  Based on bone marrow (BM) findings and on liver biopsy showing extramedullary hematopoiesis, an initial diagnosis of PMF was formulated. The patient refused stem cell transplantation from an HLA-identical sibling. [ncbi.nlm.nih.gov]

  Perform chest radiography to evaluate pulmonary manifestations.  Bone marrow examination for the presence of Gaucher’s cells is diagnostic.  Liver biopsy – Liver biopsy is occasionally performed to assess unexplained hepatomegaly. 19. [slideshare.net]

  A bone marrow or liver biopsy is not necessary to establish the diagnosis. When the specific gene mutation causing Gaucher disease is known in a family, DNA testing can be used to accurately identify carriers. [genome.gov]

  Liver disease (but not Gaucher disease [GD]) was suspected and therefore a liver biopsy was performed. [touchoncology.com]

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.

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.

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].

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].

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].

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.

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:

• Type 1 represents more than 90% of all cases and is characterized by hepatosplenomegaly, anemia, thrombocytopenia and skeletal manifestations such as osteopenia and avascular necrosis [6].
• Type 2 is distinguished by an early and aggressive onset (< 2 years) of severe neurological symptoms, including convulsions, severe mental disability and involvement of the brainstem.
• Type 3 also causes neurological symptoms, but develops usually later in life and is less severe compared to type 2 [3].

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.

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.

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