The female Gaucher patient: The impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause)

Zimran, Ari; Morris, Elizabeth; Mengel, Eugen; Kaplan, Paige; Belmatoug, Nadia; Hughes, D.A.; Malinová, Věra; Heitner, Rene; Sobreira, Elisa; Mrsić, Mirando; Granovsky-Grisaru, Sorina; Amato, Dominick; Dahl, Stephan Vom

doi:10.1016/j.bcmd.2009.04.003

Cited by 58 publications

(51 citation statements)

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“…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 .…”

Section: Discussionmentioning

confidence: 99%

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

Sekijima

Ohashi

Ohira

et al. 2010

Clinical Therapeutics

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Enzyme replacement therapy (ERT) with imiglucerase is a well-established, effective treatment for Gaucher disease. However, there have been no reports regarding the excretion of imiglucerase into human breast milk and its effects on the nursing infant.Here, we report a Gaucher disease patient who had successful pregnancies and lactation under ERT, and describe the distribution and excretion of imiglucerase in human milk. Following the peak of serum β-glucocerebrosidase activity, slightly increased enzymatic activity (0.0.16 nmol/h/mL) was observed in the first breast milk after imiglucerase infusion. Our data indicate that a small amount of imiglucerase is excreted into human breast milk.3

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Section: Discussionmentioning

confidence: 99%

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

Sekijima

Ohashi

Ohira

et al. 2010

Clinical Therapeutics

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“…46 An antenatal birth plan, taking into account all eventualities, especially hemorrhage, and method of pain relief, is ultimately the best preparation for birth. 47 A related issue is fertility, which is unimpaired in GD (female and male), and large families are not to be discouraged if this is the patient's inclination. I have some patients who have successfully undergone in vitro fertilization.…”

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confidence: 99%

How I treat Gaucher disease

Zimran

2011

Blood

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This review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one diseasespecific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer in providing adequate treatment to all symptomatic patients. The key points summarizing the way I manage my patients include accurate enzymatic diagnosis with mutation analysis (for some prognostication and better carrier detection in the family), a detailed follow-up every 6-12 months (with an option to see consultants and attention to comorbidities), and initiation of enzyme replacement therapy according to symptoms or deterioration in clinically significant features or both. I do not treat patients with very mild disease, but I consider presymptomatic therapy for patients at risk, including young women with poor obstetric history. I prefer the minimal-effective dose rather than the maximally tolerated dose, and when the difference between high-dose and lower-dose regimens is (merely statistically significant but) clinically meaningless, minimizing the burden on society by advocating less-expensive treatments is ethically justified. (Blood. 2011;118(6): 1463-1471) IntroductionThe purpose of this review is to present a cohesive approach to treating patients with Gaucher disease (GD). As can be appreciated, the spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one disease-specific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer, in providing adequate treatment for all symptomatic patients with GD. As a treating physician dedicated to GD even before the era of enzyme replacement therapy (ERT), my mandate and inspiration has always been to provide the best therapy with the least malfeasance. Description of GDGD is one of the most common glycolipid storage disorders, caused by an inherited deficiency of the lysosomal enzyme ␤-glucocerebrosidase, leading to accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system. 1 Accordingly, key disease features are related to splenomegaly with hypersplenism, hepatomegaly, and bone involvement. Although a single-gene disorder, phenotypic expression is extremely variable, ranging from totally asymptomatic (only detectable by DNA analysis or enzyme deficiency) to a lethal newborn form with hydrops fetalis and ichthyosis. Many manifestations, some notuncommon and others very rare, cannot be explained by storage per se; examples include immunologic abnormalities, increased prevalence of certain malignancies with relative paucity of ...

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“…Very rarely, the platelet response to therapy is slow or not evident (Pastores et al, 2004;Weinreb et al, 2008).It has been suggested that some patients may have a minimal or highly attenuated response to therapy because of continuing severe splenomegaly (Pastores et al, 2004), focal splenic lesions (Stein et al, 2010), and/or bone marrow involvement (Pastores et al, 2004). Apart from serving as a general disease marker in non-splenectomized patients, severe thrombocytopenia may increase the risk of spontaneous, surgical and obstetrical bleeding in GD patients (Lutsky & Tejwani, 2007;Zimran et al, 2009). Platelet counts of <20 9 10 9 /l have been reported (Zimran et al, 2005), incurring a risk of serious bleeding complications.…”

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Characteristics of type I Gaucher disease associated with persistent thrombocytopenia after treatment with imiglucerase for 4–5 years

et al. 2012

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SummaryThe characteristics of Gaucher disease (GD) associated with persistent thrombocytopenia despite imiglucerase enzyme therapy in type 1 GD (GD1) were investigated by retrospective analysis of International Collaborative Gaucher Group (ICGG) Registry data. The study involved 1016 GD1 patients with an intact spleen for whom date of diagnosis, therapy initiation, and platelet counts were known, and who received continuous imiglucerase therapy for 4 to 5 years. These patients were stratified by last platelet count: 120 9 10 9 /l (n = 772); 100 to <120 9 10 9 /l (n = 94); 80 to <100 9 10 9 /l (n = 80); and <80 9 10 9 /l (n = 70; 20 with <60 9 10 9 /l) and characterized by initial and cumulative average imiglucerase dose, body mass index, platelet count, anaemia, hepatomegaly, splenomegaly, and skeletal assessments at baseline and after 4-5 years of therapy. Statistically significant associations were found between persistent thrombocytopenia and baseline platelet count (<80 9 10 9 /l), splenomegaly, and anaemia (all P < 0·0001). After 4-5 years, statistically significant associations were found with splenomegaly (P < 0·0001), anaemia (P < 0·0001), white blood cell count (P = 0·049), hepatomegaly (P = 0·004) and bone pain (P = 0·035). Exponential platelet decay in relation to splenomegaly suggests that platelets increase only when spleen volume decreases substantially.

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The female Gaucher patient: The impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause)

Cited by 58 publications

References 101 publications

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

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

How I treat Gaucher disease

Characteristics of type I Gaucher disease associated with persistent thrombocytopenia after treatment with imiglucerase for 4–5 years

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