Researchers have identified three distinct forms of Gaucher disease separated by the absence (type 1) or presence and extent (type 2 or type 3) of neurological complications. Additional forms of Gaucher disease include perinatal-lethal form and cardiovascular form. The specific symptoms present in individuals with Gaucher disease vary greatly from person to person. Some individuals exhibit few or no symptoms (asymptomatic); others experience chronic, and sometimes severe, complications.
Gaucher disease type 1 is also known as non-neuronopathic, because it does not involve the central nervous system (brain and spinal cord). Type 1 Gaucher disease is the most common form of the condition. Most individuals with Gaucher disease type 1 experience easy bruising due to low levels of blood clotting cells known as platelets (thrombocytopenia), chronic Fatigue due to low levels of circulating red blood cells (anemia), and an abnormally enlarged liver and/or spleen (hepatosplenomegaly). Affected individuals may also experience lack of blood supply (infarction) to various bones of the body resulting in dull or intense bone Pain (bone crises), Degeneration (avascular necrosis) and deformity of affected bones, and thinning and weakening of bones (osteoporosis). Such skeletal abnormalities result in an increased susceptibility to fractures. In rare cases, affected individuals may also experience involvement of the lungs and/or kidneys.
Gaucher disease type 2, also known as acute neuronopathic Gaucher disease, occurs in newborns and infants and is characterized by neurological complications due to the abnormal accumulation of glucocerebroside in the brain. Enlargement of the spleen (splenomegaly) is often the first symptom and may become apparent before six months of age. Enlargement of the liver (hepatomegaly) is not always evident. Affected infants may lose previously acquired motor skills and exhibit Low muscle tone (hypotonia), involuntary Muscle spasms (spasticity) that result in slow, stiff movements of the arms and legs, and crossed eyes (strabismus). In addition, affected infants may experience Difficulty swallowing (dysphagia), which may result in feeding difficulties; abnormal positioning or bending of the neck (retroflexion); and failure to gain weight and grow at the expected rate (failure to thrive) and high-pitched breathing (stridor) due to contraction of the muscles of the voice box (laryngeal spasm). Anemia and thrombocytopenia may also occur. Gaucher disease type 2 often progresses to life-threatening complications such as respiratory distress or the entrance of food into the respiratory passages (aspiration pneumonia). Severely affected newborns may show skin abnormalities (collodion skin or ichthvosiform changes) and generalized swelling (hydrops), with death in the first few weeks of life. Other children with Gaucher disease type 2 have greatly reduced lifespans, with death usually occurring between 1 and 3 years of life.
Gaucher disease type 3, also known as chronic neuronopathic Gaucher disease, occurs during the first decade of life. In addition to the blood and bone abnormalities discussed above, affected individuals develop neurological complications that develop and progress slower than in Gaucher disease type 2. Associated neurological complications include mental deterioration; an inability to coordinate voluntary movements (ataxia); and brief, shock-like Muscle spasms of the arms, legs or entire body (myoclonic seizures). Some individuals with Gaucher disease type 3 may have difficulty moving their eyes from side-to-side (horizontal gaze palsy). Patients with Type 3 Gaucher disease can also have a vertical gaze palsy that usually occurs later than the horizontal gaze paresis. A significant proportion of patients also develop pulmonary (lung) disease (interstitial lung disease). There can be wide variability in presentation and clinical course among patients with type 3 Gaucher disease. Some affected patients may live into their teens and early 20’s, while others have lived for much longer (30’s and 40’s). With increasing difficulties, affected individuals may require assistance to fulfill the task of daily living (for example, with eating, bathing, and ambulation).
The perinatal-lethal form or fetal/neonatal Gaucher disease occurs in less than 5% of patients. This type is very severe and associated with death before 3 months of age or even in the womb. The fetus/newborn may present with widespread swelling of the skin (edema or anasarca) leading to fluid buildup in the heart, skin, or lungs (hydrops fetalis). Other symptoms include bleeding within the skull (intracranial hemorrhage), scaling of the skin (non-bullous ichthyosiform erythrodema) with a reddish appearance, and contraction of the joints in fixed, bent position (arthrogryposis multiplex congenita).
The cardiovascular form is characterized by CNS involvement, such as having difficulty initiating eye movement in desired directions (oculomotor apraxia). Other symptoms include calcification of the mitral and aortic valve, corneal opacity, and mild splenomegaly. Calcium deposits on the heart can reduce blood flow to these valves, and can increase blood pressure. Supranuclear ophthalmoplegia can also be present, which causes problems with balance, walking, and thinking. Cardiac-related complications and associated neurologic problems lead to a reduced lifespan, although this can extend into young adulthood in some patients.