Gaucher Disease Type II - A rare genetic disorder

Introduction

A familial disorder that is autosomal recessive due to faulty metabolism of the lipoid kerasin. Lack of glucocerebrosidase results in the accumulation of glucosylceramide within lysosomal cells of macrophages and monocytes lineage with reticular cells and histiocytes increase, and many become infiltrated with kerasin. As a result, they accumulate in the patient's bone anemia marrow.

Types of gaucher diasese

• Type I (chronic non-neuropathic): There is no cerebral involvement.

• Type II (acute neuropathic): It is characterized by hepatosplenomegaly and central nervous system disorders.

• Type III (subacute neuropathic): It resembles type II but later in onset and has a more protracted clinical course.

What is Type 2 Gaucher Disease?

Gaucher disease is a multisystemic lipidosis portrayed by hematologic oddities, organomegaly, and skeletal involvement, usually presenting with bone pain and pathologic fractures. It is considered one of the most common lysosomal storage disorders and the most prevalent hereditary defect among Ashkenazi Jews. Type 2 Gaucher disease is an extremely rare condition, rapidly progressive, affecting the brain (central nervous system), the spleen, the liver, the lungs, and bones. Infantile Gaucher disease is characterized by extreme neurological (brain) involvement in the twelve months of life. It is also called acute neuronopathic Gaucher disease and presents as 1 in 100,000 newborns having type two diseases with no ethnic predilection. Infants usually appear normal at birth but evolve symptoms by 3 to 6 months. Type 2 is almost always evident by six months of age. The vast prevalence of children dies over two years. Nevertheless, a small number have survived slightly longer.

What is the Etiology of Type 2 Gaucher Disease?

Gaucher disease type 2 is a lysosomal storage disease caused by a mutation in the GBA gene (1q21) that regulates the lysosomal enzyme glucocerebrosidase. The deficiency in glucocerebrosidase causes the accumulation of glucosylceramidase or beta-glucocerebrosidase deposits in the cells of the reticuloendothelial system of the liver, of the spleen and the bone marrow called Gaucher cells.

What Are the Sign and Symptoms of Type 2 Gaucher Disease?

Signs and symptoms included

• There is an enlargement of the lymph nodes, spleen, and to a lesser extent, the liver (hepatosplenomegaly).

• Bone pain due to changes in the bone marrow.

• There is often bleeding from the nose or the gums.

• Teeth extraction from the affected area may result in bleeding complications and CNS involvement.

• The patient also suffers from anemia and thrombocytopenia.

• The skin is sometimes pigmented, and the conjunctival fibrous tissue may be thickened and of brownish discoloration, a condition known as ' pingueculae.'

• The prognosis is very poor; the disease results in death, usually within the first year.

• The rigidity of the neck and limbs (hypertonia).

• Head thrust back.

• Lockjaw (trismus).

• Squinting (strabismus).

• Difficulty swallowing.

• Vocal cord (laryngeal) spasms.

• Seizures and a failure to shake off chest infections.

Neurological symptoms of Gaucher disease types two and three include:

• Feeding challenges and developmental delays.

• Cognitive difficulties.

• Eye problems, especially when moving the eyes from side to side.

• Difficulties with gross motor skills and coordination.

• Seizures, muscle spasms, and jerky movements.

What Is the Investigation For Type 2 Gaucher Disease?

Radiographic Features:

• Rarefaction: Bone changes occur due to destructive infiltration of the cerebrosides reticulosis of the bone marrow. As a result of this and the proliferation of cells so-called Gaucher cells, the bone undergoes rarefaction.

• Porosity: There may be generalized porosity of the mandible and maxilla, with loss of trabecular structure. Sometimes, there is porosity in the mental region and thinned-out mandibular cortex, and areas of osteolysis are present in the osteolysis maxillary premolar area.

• Worm-eaten appearance: Pseudocystic radiolucent areas in the molars and premolars with a 'worm-eaten appearance' can be seen.

• Laboratory Diagnosis: Biopsy of spleen and liver show typical Gaucher cells, which are round pale cells containing a small eccentric nucleus and wrinkled or crumpled silk cytoplasm.

What is the Treatment for Gaucher disease?

There is no cure for the neurological impairment from Gaucher disease types 2 and 3. Treatment for Gaucher disease includes

• Enzyme replacement therapy (ERT): an enzyme infusion IV intravenously (via a vein in the arm) gives the enzyme directly into the bloodstream, from where it can reach the organs and bones to break down fatty chemicals.

• Substrate reduction therapy (SRT): This treatment diminishes fatty chemicals so they can not build up in the body.

• And other genetic engineering and stem cell technologies-based medicine.

What Are the Complications of Gaucher Disease?

Gaucher disease can induce additional health issues such as:

• Delayed growth: It affects the normal balance physiological cycle.

• Delayed puberty: It causes the late onset of puberty.

• Weak bones: Mostly affect the skeleton, including bone pain and joint ache.

• Brain damage: Gaucher disease mainly affects the brain and central nervous system.

• Disruption of walking or getting around.

• Anemia: Reduce the number of red blood cells in the blood which ultimately manifests as pallor fatigue and stomatitis.

• Fatigue: Excessive tiredness in daily routine tasks.

What Can a Person do to Prevent Gaucher Disease?

If Gaucher's disease drives in the family, consult with a genetic counselor. It is better to get help and find out the risk of having the disease. And should genetically determine the chances of passing on the disease to the offspring or their children. Testing the brother or sister of an individual with Gaucher disease can help notice the disease early.

Conclusion

As the disorder runs in the families, one should notify the siblings and other members with Gaucher disease. Screening the cause or gene mutation can help manage the diseases with effective outcomes. Gaucher disease is a familial disorder with a deficiency of glucocerebrosidase enzyme. Type two is an infant disorder with neurological manifestations with skeleton involvement. It is better to consult the experts at the right time for better management and great outcome.