How Gaucher disease is manifested and diagnosed

A genetic disease whose basis is a disorder of lipid metabolism, deficiency of lysosomal enzymes, and cumulation of glycolipids in cells is called Gaucher disease (sphingolipidosis, glucosylceramide lipidosis). The symptomatology is correlated with the type of disease. What are the general and specific signs of the pathology, how the diagnosis is made and the symptoms are corrected, you will learn from the article.


  1. General information.
  2. Causes.
  3. Pathogenesis.
  4. Symptoms.
  5. Complication.
  6. Diagnosis.
  7. Treatment.
  8. Prognosis and prevention.

General information

The disease is named after the French doctor F. Gaucher, who described its symptoms at the end of the 19th century. Gaucher disease belongs to the group of lysosomal accumulation diseases, the basis of which are gene mutations with changes in functions of cell organelles of lysosomes. According to statistics, the prevalence of this pathology is between 1 in 40,000 and 1 in 70,000. It is most common in places where marriages between close relatives are legalized (Ashkenazi Jews, for example). One in 400 people is a carrier of the mutation.


The main trigger for glucosylceramide sphingolipidosis is a defect in the GBA gene, which controls the enzyme glucocerebrosidase, which is responsible for the breakdown of fats. Inheritance is autosomal recessive, requiring a pair of mutation genes: from the mother and father to form the pathology. Where both parents are carriers of the gene, there is a 25% risk of giving birth to a sick infant. The risk of passing on a mutation gene with the development of a carrier in such married couples is 50%. The presence of two defective alleles in the genotype reduces glucocerebrosidase capacity by one-third of normal.


The basis of the pathology is the minimization of the catalytic activity of beta-glucosidase. As a result, the breakdown of complex compounds of lipids and carbohydrates to glucose and ceramide is impaired. Abnormally fast accumulation of macromolecules in cells with high rate of renewal, i.e. in macrophages. Unhydrolyzed fats accumulate in lysosomes, forming special accumulation cells – Gaucher cells.

Primary metabolic failure provokes secondary disorders of cellular functions and causes leptin resistance. Because of abnormalities in lipid metabolism, a syndrome of macrophage activation, monocytopoiesis with maximal macrophages in the liver, spleen, bone marrow is formed. This presents a risk of splenomegaly, hepatomegaly, bone marrow infiltration. Macrophage dysregulation provokes cytopenia with bone and joint damage.


According to the age at which the debut of the pathology occurs, there are three types of pathology:

  1. The first is characterized by the chronicization of the process, the symptoms appear by the age of 30-40: hepatomegaly, splenomegaly, anemia, increased bleeding. Depression of the hematopoietic system minimizes the concentration of hemoglobin and platelets, changes in the musculoskeletal system are visualized by pain syndrome, fractures, and bone deformities. In adult patients, the skin darkens, hyperpigmentation occurs, flat red spots appear in the periorbital area, and patients are stunted.
  2. The second type, which is called acute infantile or acute neuropathic, is rare. The pathology debuts from birth to a year and a half and is manifested by a rapid course, resistance to therapy, and neurologic disorders. Babies are lethargic, poorly sucking, weakly crying, impaired swallowing reflex, respiratory disorders, mental and physical developmental delays are observed. At the beginning of the disease, muscle tone is reduced, which in a year becomes hypertonic, provoking seizures, spastic paralysis, strabismus. Inflammation of the lungs is common, always hepatosplenomegaly.
  3. The third type, called juvenile or neuropathic, debuts at age three, and all symptoms unfold before age 15 and include CNS lesions with muscle hypertonus, strabismus, spastic paralysis, seizures, breathing difficulties, problems in swallowing. Mental disorders are manifested by decreased intelligence, poorly developed speech, writing, emotional instability. The child lags behind in sexual development, and the pathology is constantly progressing.


The complications of the second and third types of pathology are the most serious. Involvement of the spinal cord and brain provokes the respiratory cycle, sudden respiratory arrest, laryngeal spasm, and death by suffocation. A low platelet count becomes a trigger for internal bleeding. The first type in the form of complications gives brittle bones, secondary infection, limitation of patients’ mobility and their need for nursing care.


Diagnosis can be made by clinical symptomatology: history with hereditary predisposition, typical signs: short stature, bone abnormalities, strabismus, unstable gait, paralysis, hemorrhagic syndrome, hyperpigmentation of the dermis. Sometimes the suspicion of the disease occurs accidentally on the basis of OAC, ultrasound examination with hepato- and splenomegaly, depressed hematopoiesis.

To confirm the diagnosis it is carried out:

  • OAC and biochemical testing;
  • analysis of cellular enzymes;
  • evaluation of bone marrow morphology;
  • examination of bone structure;
  • ultrasound, MRI of the liver and spleen;
  • DNA diagnostics – not mandatory, but can confirm gene mutations, which is necessary when all previous tests are ambiguous.


A set of corrective measures for patients with type 1 and type 3 is aimed at eliminating the symptoms of the primary genetic defect. With type 2 pathology, the therapeutic measures are limited to alleviating the clinic.

The general regimen includes:

  1. Lifelong replacement enzyme therapy with recombinant glucocerebrosidase. Efficiency is sufficient: symptoms are relieved, patients’ quality of life improves. The drugs are used for the third and first type of pathology, administered intravenously.
  2. Substrate-reducing therapy – a new direction in the treatment of Gaucher disease, aimed at reducing the rate of glycosfingolipid production and accelerating the catabolism of accumulating macromolecules. Specific glucosylceramide synthase inhibitors are used, which are effective in type 1 pathology.
  3. Symptomatic correction is prescribed for the treatment of osteoporosis, skeletal complications. Calcium-containing drugs, vitamin D, calcium-enriched diet, nonsteroidal anti-inflammatory drugs, antibiotics are used. Neurological symptoms are treated with antiepileptic drugs, nootropics, muscle relaxants.

Prognosis and prevention

With type 1 pathology, the prognosis is most favorable, since it is possible to normalize the glucocerebrosidase functionality and prevent complications and avoid disability. With type 3, the prognosis is correlated with the course of the pathology and the body’s individual response to correction. At type 2 the prognosis is fatal.

Prevention implies a number of measures during pregnancy planning. All those with a history of hereditary aggravation require medical-genetic consultation. If there is a high risk of hereditary mutation, the enzyme concentration in the amniotic fluid is tested in the first trimester of pregnancy, deciding whether to terminate the pregnancy.

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