Gaucher Disease

INTRODUCTION & BASICS

Gaucher disease (GD) is the most common disorder among Lysosomal storage disorders (LSD) worldwide and in India. Lysosomal storage disorders are a group of more than 40 inherited metabolic disorders characterized by impaired lysosomal function leading to accumulation of substrates within the organelle. GD is caused due to a metabolic defect ie. Deficiency of an enzyme called Glucocerebrosidase caused due to genetic changes(mutations) in the gene responsible for its production(GBA1/Acid-B-glucosidase gene). This results in accumulation of the substrate (glucosylceramide) in the lysosomes of macropahges leading to a wide spectrum of manifestations.

IMPORTANCE OF GD

GD is one of the most common metabolic disorders in India. This is partly due to the practice of consanguineous marriages in India
GD is the most treatable LSD due to the availability of Enzyme Replacement Therapy

CLASSIFICATION OF GD

Three types of GD have been described based on clinical features, ethnicity and natural history of the disease.

Type I GD: Most common type among GD. Type I does not show any neurological involvement

Type II GD/Acute Neuronopathic GD/ Infantile Cerebral GD: Comprises about 1 % of GD patients

Type II GD: It is a chronic neuronopathic form and is seen in 5 % of patients overall

In India about two-thirds have been found to have GD3 and a third to have GD1

CLINICAL PRESENTATION

The clinical presentation is variable and shows overlap between the 3 types. The major organs involved, with their clinical manifestations are given below:

Visceral Organs: Hepatomegaly, Splenomegaly

Hematological: Anemia, Thrombocytopenia

Skeletal: Chronic bone pain, Bone fractures, skeletal growth retardation, osteopenia

Heart: Congestive heart failure

Eyes: Occular motor apraxia

Central Nervous System: Seizures, Hypotonia, Rigidity, Dementia, Mental Retardation

DIAGNOSIS

Diagnosis of Gaucher disease is made on the basis of clinical history, physical examination, laboratory tests and confirmed by a blood test showing deficient glucocerebrosidase enzyme and genetic (DNA) analysis for the causal gene defects (mutations) in the GBA gene.

TREATMENT/MANAGEMENT

The main goal is to improve the patients’ quality of life by allowing them to perform their normal daily by reducing the accumulation of the toxic substrate glucocerebroside and other glycolipids. The treatment options currently available are

Enzyme Replacement Therapy: where the deficient enzyme is administered in its modified form. ERT has revolutionized the treatment of Gaucher disease and has now become the standard of care It has offered hope to patients with this disease who otherwise have a dismal prognosis. Enzyme replacement therapy (ERT) has proven effective for individuals with Gaucher disease type 1. ERT has not been too successful in Type 2 &3. The two FDA approved ERT are imiglucerase (Cerezyme) from Genzyme and Velaglucerase alfa (trade name VPRIV) from Shire.

Substrate Reduction Therapy: Substrate (glucocerebroside) depletion through inhibition of glucosylceramide synthase enzyme are used for milder disease where treatment with ERT is not possible. The two current FDA-approved drugs include eliglustat (Cerdelga) and imiglustat (Zavesca)

Bone marrow transplantation has the potential for cure of GD. Bone marrow transplant was the only treatments available prior to introduction of ERT. Since the availability of effective ERT bone marrow transplant is no longer the treatment of choice as it has significant morbidity and mortality associated with it.

Counseling: Psychological counseling is important for patients and families with GD given the likelihood of incapacitating symptoms and chronic nature of the disease. When the parents are heterozygous carriers of the genetic defect, each child will have a 25% chance of having the disease.

Future Therapies Being Investiagted: Enzyme Enhancement Therapy with Chaperones, Gene Therapy

GD IN INDIA

Gaucher disease is found to be the commonest LSD in India. There has been a drastic increase in the number of Gaucher patients due to availability of the diagnostic blood test and also since treatment options particularly ERT is available. ERT is profoundly expensive and virtually beyond the means of any patient. The INCAP (India Charitable Access Programmed) of Genzyme Corporation, USA and similar support from Shire pharmaceuticals has made it possible for some patients of Gaucher disease to get ERT free of cost.

Note:

If you know anyone with Gaucher Disease, or if you are a physician interested in collaboration, please get in touch with the ORDI team.

Contact for Free Diagnostic test of Gaucher disease.

Write to us: contactus@ordindia.in

Rare Disease helpline -+91 8892 555 000

RESOURCES