Management of non‐neuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring

Abstract

Enzyme replacement was introduced as treatment for non-neuronopathic Gaucher disease more than 15 years ago. To ensure the best use of this costly ultra-orphan agent, a systematic disease management approach has been proposed by an international panel; this includes the development, by consensus, of achievable treatment goals. Here we critically review these goals and monitoring guidelines and incorporate emerging experience of the disease in the therapeutic era, as well as contemporary clinical research. This review makes recommendations related specifically to the management of pregnancy; the appropriate use of splenectomy and bisphosphonate treatment; the relevance of biochemical markers to disease monitoring; and the use of semi-quantitative methods for assessing bone marrow infiltration. In addition, we identify key areas for development, including the requirement for a validated index of disease severity; the need to correlate widely used biomarkers with long-term disease outcomes, and the desirability of establishing agreed standards for monitoring of bone disease particularly in infants and children with Gaucher disease.

Successful pregnancy and lactation outcome in a patient with Gaucher disease receiving enzyme replacement therapy, and the subsequent distribution and excretion of imiglucerase in human breast milk

“…However, these guidelines make no specific reference to female patients during pregnancy and lactation. There is accumulating evidence that ERT with imiglucerase before and during pregnancy could place the patient in an optimal condition to withstand the excess physiological impact of pregnancy, reduce the incidences of spontaneous abortion and complications during delivery and the postpartum period 6,7,11,12 . In addition, there is no evidence of adverse effects of imiglucerase on the fetus 6,7,11,12 .…”

Velaglucerase alfa

“…ERT is now the standard of care for symptomatic type 1 Gaucher's disease 1,2 . Imiglucerase (Cerezyme; Genzyme), a recombinant analogue of β-glucocerebrosidase produced in Chinese hamster ovary cells 2,4 , was approved by the FDA in 1994 and largely replaced alglucerase.…”

“…Gaucher's disease is a rare genetic disorder caused by mutations in the gene that codes for the lysosomal enzyme β-glucocerebrosidase, which catalyses the metabolism of the sphingolipid glucocerebroside 1 . Owing to the resultant deficiency in β-glucocerebrosidase activity, glucocerebroside accumulates, primarily in the lysosomal compartment of macrophages 1 .…”

“…Owing to the resultant deficiency in β-glucocerebrosidase activity, glucocerebroside accumulates, primarily in the lysosomal compartment of macrophages 1 . The presence of such cells in the bone marrow and the spleen leads to anaemia and thrombocytopenia, and their accumulation in the liver and the spleen results in the enlargement of these organs 1 .…”

Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent

“…[9][10][11][12] Each has proven effective in the management of the key disease manifestations, including a reduction in organomegaly, improvements in the blood counts and biochemical parameters, a decrease in bone-related pain (but not reversal of existing pathology) and compensatory growth in children. [13][14][15][16][17][18] ERT has also been remarkably safe, and the few adverse effects that have been reported are typically mild and transient in nature. [19][20][21][22][23] There have been no reports of any obvious toxicity because of overdose.…”