Gauchers disease

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GAUCHER DISEASE
• This disease is a multisystemic lipidosis characterized by hematologic
abnormalities, organomegaly, and skeletal involvement, the latter
usually manifesting as bone pain and pathologic fractures .
• It is one of the most common lysosomal storage diseases and the
most prevalent genetic defect among Ashkenazi Jews.

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There are 3 clinical subtypes delineated by the absence or presence
and progression of neurologic manifestations:
• type 1 or the adult, nonneuronopathic form
• type 2, the infantile or acute neuronopathic form
• type 3, the juvenile or subacute neuronopathic form. All are
autosomal recessive traits.
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Clinical manifestations
Gaucher Diz. type 1
• Thrombocytopenia & its manifestation
• Anemia & its manifestation
• Hepatomegaly with or without elevated liver function test results
• Splenomegaly
• Bone pain.
• Pulmonary involvement
• Growth retardation
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Gaucher disease type 2
• is a rare form and does not have an ethnic predilection. It is
characterized by a rapid neurodegenerative course with extensive
visceral involvement and death within the first years of life.
• It presents in infancy with increased tone strabismus organomegaly
Failure to thrive stridor caused by laryngospasm psychomotor
regression death typically occurs secondary to respiratory
compromise.
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Gaucher disease type 3
• presents with clinical manifestations that are intermediate to those
seen in types 1 and 2, with presentation in childhood and death by
age 10-15 yr. It has a predilection for the Swedish Norrbottnian
population, among whom the incidence is approximately 1 in 50,000.
• Neurologic involvement is present.
• Type 3 disease is further classified as types 3a and 3b based on the
extent of neurologic involvement and whether there is progressive
myotonia and dementia (type 3a) or isolated supranuclear gaze palsy
(type 3b).
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Gaucher disease should be considered in the differential diagnosis
of
• patients with unexplained organomegaly,
• who bruise easily,
• have bone pain,
• or have a combination of these conditions
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Diagnosis
• Prenatal diagnosis is available by determination of enzyme activity
and/or the specific family mutations in chorionic villi or cultured
amniotic fluid cells.
• New Born Screening for IEM-TMS with DBS
• Bone Marrow examination
• Definitive Diagnosis
- Demonstration of deficiency of enzyme activity
-Detection of Pathogenic Mutations in GBA1 gene
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• The management goal chiefly includes restoring normal values,
preventing complications, and eliminating or reducing signs and
symptoms of GD
• Most short-term goals, except platelet count, are targeted in the
first two years of treatment
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Treatment of patients with Gaucher disease type 1
• includes enzyme replacement therapy. The efficacy of enzyme
replacement therapy with mannose-terminated recombinant human
acid β-glucosidase has definitively been demonstrated.
• Most symptoms (organomegaly, hematologic indices, bone pain) are
reversed by enzyme replacement therapy (60 IU/kg) administered by
intravenous infusion every other week and the bone involvement can
be stabilized or improved.
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• A two additional enzyme preparations are approved by the FDA for
the treatment of type 1 Gaucher disease, including
• velaglucerase alfa (VPRIV, Shire HGT), which is produced in human
fibrosarcoma cells, and
• taliglucerase alfa (Uplyso, Protalix Biotherapeutics), which is produced
in carrot cells.
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Major centres in India having expertise in administering ERT are situated in
Bengaluru (Indira Gandhi Institute of Child Health & Center for Human
Genetics), Chennai (Fetal CareResearch Foundation), Hyderabad (Rainbow
Children's Hospital), Kochi (Amrita Institute of MedicalSciences), Lucknow
(Sanjay Gandhi Postgraduate Institute of Medical Sciences), Mumbai (KEM
Hospitaland Jaslok Hospital), and New Delhi (AIIMS and Sir Ganga Ram
Hospital).
Ref: Muranjan M, Karande S. Enzyme replacement therapy in India: Lessons and insights. J Postgrad Med. 2018;64(4):195-9.
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• A small number of patients have undergone bone marrow
transplantation (BMT), which is curative but is associated with
significant morbidity and mortality from the procedure, limiting the
selection of appropriate candidates.
• Gene Therapy under trials
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