See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism Approach to the Patient With a Suspected Inherited Disorder of Metabolism Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more .
Glucocerebrosidase normally hydrolyzes glucocerebroside to glucose and ceramide. Genetic defects of the enzyme cause glucocerebroside accumulation in tissue macrophages through phagocytosis, forming Gaucher cells. Accumulation of Gaucher cells in the perivascular spaces in the brain causes gliosis in the neuronopathic forms.
There are 3 types of Gaucher disease, which vary in epidemiology, enzyme activity, and manifestations.
Type I Gaucher disease
Type I (nonneuronopathic) is most common (90% of all patients). Residual enzyme activity is highest. Ashkenazi Jews are at greatest risk; 1/12 is a carrier. Onset ranges from childhood to adulthood.
Symptoms and signs of type I Gaucher disease include splenohepatomegaly, bone disease (eg, osteopenia, pain crises, osteolytic lesions with fractures), growth failure, delayed puberty, ecchymoses, and pingueculae. Epistaxis and ecchymoses resulting from thrombocytopenia are common.
X-rays show flaring of the ends of the long bones (Erlenmeyer flask deformity) and cortical thinning.
Type II Gaucher disease
Type II (acute neuronopathic) is rarest, and residual enzyme activity in this type is lowest. Onset occurs during infancy.
Symptoms and signs of type II Gaucher disease are progressive neurologic deterioration (eg, rigidity, seizures) and death by age 2 years.
Type III Gaucher disease
Type III (subacute neuronopathic) falls between types I and II in incidence, enzyme activity, and clinical severity. Onset occurs at any time during childhood.
Clinical manifestations vary by subtype and include progressive dementia and ataxia (IIIa), bone and visceral involvement (IIIb), and supranuclear palsies with corneal opacities (IIIc). Patients who survive to adolescence may live for many years.
Diagnosis of Gaucher Disease
Diagnosis of Gaucher disease is by DNA analysis and/or enzyme analysis of white blood cells. Carriers are detected, and types are distinguished by mutation analysis. Although biopsy is unnecessary, Gaucher cells—lipid-laden tissue macrophages in the liver, spleen, lymph nodes, bone marrow, or brain that have a wrinkled tissue-paper appearance—are diagnostic. (Also see testing for suspected inherited disorders of metabolism Initial testing Most inherited disorders of metabolism (inborn errors of metabolism) are rare, and therefore their diagnosis requires a high index of suspicion. Timely diagnosis leads to early treatment and... read more .)
Treatment of Gaucher Disease
Types I and III: Enzyme replacement with glucocerebrosidase
Sometimes miglustat, eliglustat, splenectomy, or stem cell or bone marrow transplantation
Enzyme replacement with IV glucocerebrosidase is effective in types I and III; there is no treatment for type II. The enzyme is modified for efficient delivery to lysosomes. Patients receiving enzyme replacement require routine hemoglobin and platelet monitoring, routine assessment of spleen and liver volume by CT or MRI, and routine assessment of bone disease by skeletal survey, dual-energy x-ray absorptiometry scanning, or MRI.
Miglustat (100 mg orally 3 times a day), a glucosylceramide synthase inhibitor, reduces glucocerebroside concentration (the substrate for glucocerebrosidase) and is an alternative for patients unable to receive enzyme replacement.
Eliglustat (84 mg orally once a day or 2 times a day), another glucosylceramide synthase inhibitor, also reduces glucocerebroside concentration.
Splenectomy may be helpful for patients with anemia, leukopenia, or thrombocytopenia or when spleen size causes discomfort. Patients with anemia may also need blood transfusions.
Bone marrow transplantation or stem cell transplantation provides a definitive cure but is considered a last resort because of substantial morbidity and mortality.
Gaucher disease is a sphingolipidosis resulting from glucocerebrosidase deficiency, causing deposition of glucocerebroside.
There are 3 types, which vary in epidemiology, enzyme activity, and manifestations.
Symptoms and signs vary by type but are most commonly hepatosplenomegaly or central nervous system changes.
Diagnosis of Gaucher disease is by DNA analysis and/or enzyme analysis of white blood cells; carriers are detected, and types are distinguished by mutation analysis.
Treatment for types I and III include enzyme replacement with glucocerebrosidase, and sometimes miglustat, eliglustat, splenectomy, or stem cell or bone marrow transplantation; there is no treatment for type II.
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man® (OMIM®) database: Complete gene, molecular, and chromosomal location information