Gaucher Disease

Abstract

Gaucher disease is the most frequent lysosomal storage disorder. It is an autosomal recessive condition caused by a functional deficiency of the enzyme β-glucosidase, which results in accumulation of glucosylceramide in lysosomes of macrophages of the reticuloendothelial system. The most prevalent form of Gaucher disease is type 1 variant, a form that does not affect the central nervous system. Progressive accumulation of Gaucher cells leads to multiple manifestations, including hepatosplenomegaly, anemia, thrombocytopenia, growth retardation, pulmonary infiltrates, and skeletal disease. Radiographically demonstrable involvement results from five basic processes: marrow replacement, generalized osteopenia, skeletal resorption due to heavily involved marrow leading to focal lytic lesions (sometimes with extraosseous extensions, also known as gaucheromas), acute focal bone disease (such as osteonecrosis, especially collapse of the femoral head, osteomyelitis, and fractures), and the Erlenmeyer flask deformity, a highly characteristic but inconstant and not pathognomonic, modeling abnormality of the distal femur. Dual-energy X-ray absorptiometry demonstrates low levels of bone density and is superior to quantitative CT scans in Gaucher disease patients, because it takes into account cortical bone loss. Magnetic resonance imaging is the cornerstone of skeletal imaging in Gaucher disease. Affected bone marrow characteristically demonstrates low signal intensity on both T1-weighted and nonfat-suppressed T2-weighted imaging sequences, and it is relatively hyperintense on fat-suppressed sequences, such as short tau inversion recovery. The pattern of involvement can be homogeneous or heterogeneous. Gaucher disease extends into the marrow in a fairly predictable pattern, which reverses the sequence of normal marrow conversion during childhood, the process known as reconversion, as may also be seen in other marrow-replacing disorders. The most sensitive MRI technique that is currently available to quantify the extent of marrow replacement is quantitative chemical shift imaging. This technique quantifies the fat content in bone marrow by using the difference in resonant frequencies between fat and water. The fat fraction is decreased severalfold in patients with Gaucher disease, compared with normal individuals, as Gaucher cells displace the normal triglyceride-rich adipocytes in bone marrow. A number of semiquantitative scoring systems have been created that use more widely available MRI technology. These include the Düsseldorf Gaucher score, the vertebra-to-disk ratio, and the bone marrow burden score, as well as other scales based on the known pattern of disease progression and visual determination of the presence of disease. Radioisotope scans, including technetium (Tc)-99 m sulfur colloid, ^99mTc sestamibi, and bone scanning after inhalation of xenon gas, have also been used to evaluate the marrow changes of Gaucher disease. Ultrasonography may be used to assess volume changes in the liver and spleen. Intravenous enzyme replacement therapy (ERT) is an effective treatment for the systemic manifestations of Gaucher disease. ERT has the potential to prevent serious skeletal complications as well as suppress disease manifestations. More recently developed oral substrate reduction therapies attenuate the rate of synthesis of glucocerebroside and provide an alternative for symptomatic adult patients for whom ERT is not an option. Imaging helps guide management decisions by assessing the sites and degrees of organ involvement, monitoring treatment response, and detecting complications.