Gaucher disease: symptoms, causes and types

Lysosomal storage diseases are associated with poor functioning of certain enzymes, which causes the accumulation of lipids and proteins in cells.

In this article we will analyze the symptoms, causes and the three types of Gaucher diseaseThe most common of this type of disorder, which affects several functions of the body.

    What is Gaucher disease?

    Gaucher disease is a disease caused by genetic mutations transmitted by autosomal recessive inheritance. It affects the blood, brain, spinal cord, bones, liver, spleen, kidneys, and lungs, and severe forms of deterioration lead to death or drastically reduce life expectancy.

    It was described by Philippe Gaucher, a French physician specializing in dermatology, in 1882. Initially, Gaucher believed that symptoms and signs were manifestations of a specific class of spleen cancer; It was not until 1965 that the real underlying causes, related to biochemical and non-immune aspects, were identified.

    Gaucher disease belongs to a group of conditions called “Diseases of lysosomal storage” or “by lysosomal storage”, Linked to a deficiency of enzymatic function. It is one of the most common in this group, as it occurs in about 1 in 40,000 births.

    The prognosis of this disease depends on which of the three existing variants we refer to. Type 1, the most common in the West, it can be managed with enzyme replacement therapies and reduce the concentration of accumulated substances causing the pathology, while the neurological signs of types 2 and 3 are not treatable.

      Main symptoms and signs

      Gaucher disease causes damage in many different organs and tissues, as well as in the blood; this explains the appearance of signs of varied character. A key criterion for determining the severity of the disease is the presence or absence of neurological damage, which is life threatening and significantly interferes with development.

      Among the most common symptoms and signs and highlights of Gaucher disease, we find the following:

      • Enlarged liver and spleen (hepatosplenomegaly) which causes inflammation of the abdomen
      • Pain in bones and joints, arthritis, osteoporosis and increased frequency of bone fractures
      • Anemia (decrease in the number of red blood cells) that causes fatigue, dizziness or headache
      • Increased ease with which bruises form and bleed
      • Increased risk of developing diseases in the lungs and other organs
      • Yellowish or brown pigmentation of the skin
      • Brain damage, impaired brain development, apraxia, Convulsions, muscular hypertension, abnormal eye movements, apnea, odor deficits (in case of neurological disorders)

      Causes and pathophysiology

      Gaucher disease appears as a result of glucocerebrosidase enzyme deficiency, Which is located in the membranes of lysosomes (cell organelles that contain a large number of enzymes) and has the function of breaking down fatty acids of the glucocerebroside class, as well as others of different types.

      Alterations in the function of glucocerebrosidase make it impossible to adequately remove certain substances from lysosomes. Hence, they accumulate in the body giving rise to the symptoms of Gaucher disease. There are other disorders with similar causes, such as Tay-Sachs disease, Hunter disease or Pompe disease.

      In the case of Gaucher disease, these changes are due to a genetic mutation transmitted by autosomal recessive inheritance. Therefore, in order for it to affect a person, he must have inherited the genetic defect from both his father and mother; if both parents have it, the risk of suffering from the disease is 25%.

      The mutation causing symptoms varies depending on the variant of Gaucher disease, but is always linked to the beta-glucosidase gene, located on chromosome 1. About 80 different mutations were found which were grouped into three categories; to these we will devote the following section.

        Types of Gaucher disease

        In general, Gaucher disease is divided into three types depending on the severity of the neurological disorders: type 1 or non-neuropathic, type 2 or acute acute neuropathic and type 3 chronic neuropathic.

        It is important to note that the validity of this categorization has been questioned and accused of reductionism by several experts.

        1. Type 1 (non-neuropathic)

        Type 1 is the most common variant of Gaucher disease in Europe and the United States; in fact, about 95% of cases detected in these regions fall into this category. The term “non-neuropathic” refers to the absence or slight damage to the central nervous system.

        In people with type 1 Gaucher disease, no alteration in brain development is observed, unlike in types 2 and 3. The most notable symptoms include feeling tired, enlarged brain. spleen and liver and bone problems.

        2. Type 2 (acute acute neuropathic child)

        Acute neuropathic-type Gaucher disease in children is the most severe form of the disease. It causes irreversible brain damage and neurological abnormalities, Including brainstem malformation, for which there is no treatment at present, and usually results in the death of the affected child before the age of 2 years.

        3. Type 3 (chronic neuropathy)

        Although the chronic neuropathic type is rare in Western countries, it is the most common variant in the rest of the world. The severity of type 3 is midway between that of types 1 and 2: It causes class 1 symptoms but also neurological disorders, and reduces life expectancy to less than 50 years.

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