Gaucher's disease with myocardial involvement in pregnancy

Torloni, Maria Regina; Franco, Kátia; Sass, Nelson

doi:10.1590/s1516-31802002000300008

Cited by 21 publications

(18 citation statements)

References 5 publications

(2 reference statements)

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“…Several case reports confirm that pregnancies usually proceed to term in Gaucher patients, despite disease manifestations such as hepatosplenomegaly (Ayhan et al 1996) and portal hypertension (Mazor et al 1986), and even with rare complications such as myocardial involvement (Torloni et al 2002) and disseminated intravascular coagulation (Clarkson et al 1998). Hepatosplenomegaly rarely restricts fetal growth, although abdominal discomfort, bloating, early satiety, heartburn, and low back pain are likely to be aggravated in untreated pregnant Gaucher patients (Tordjeman et al 1991).…”

Section: Resultsmentioning

confidence: 99%

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

Cox¹,

Aerts²,

Belmatoug³

et al. 2008

J of Inher Metab Disea

121

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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.

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Section: Resultsmentioning

confidence: 99%

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

Cox¹,

Aerts²,

Belmatoug³

et al. 2008

J of Inher Metab Disea

121

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“…The altered ratio of GlcCer to ceramides leads to an alteration of the hydrophobic barrier, decreased keratinocyte desquamation (Eblan et al 2005;Holleran et al 1994;Sidransky et al 1992) and their increased proliferation (Marsh et al 1995). Further, the myocardial involvement observed in GD (Platzker et al 1985;Torloni et al 2002) has been explained solely by the infiltration of the heart by GCs (Edwards et al 1983;Smith et al 1978), while the syndrome of pulmonary hypertension is thought to be caused by GCs occupying the lumina of the alveolar capillaries or alveoli (Mistry et al 2002), although this syndrome has been described in the absence pulmonary GCs (Theise and Ursell 1990). Lastly, bone involvement leading to 'bone crises' (Beighton et al 1982) is also awaiting an explanation that goes beyond the mere presence of GCs (Fiore et al 2002;Stowens et al 1985;Wenstrup et al 2002).…”

Section: Glucosylceramide Transfermentioning

confidence: 99%

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Elleder

2006

J of Inher Metab Disea

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SummaryGaucher disease (GD), deficiency of acid glucosylceramidase (GlcCer‐ase) is characterized by deficient degradation of beta‐glucosylceramide (GlcCer). It is well known that, in GD, the lysosomal accumulation of uncleaved GlcCer is limited to macrophages, which are gradually converted to storage cells with well known cytology—Gaucher cells (GCs). On the basis of previous studies of the disorder and of a comparison with other lysosomal enzymopathies affecting degradation of the GlcCer‐based glycosphingolipid series, it is hypothesized that in other cell types (i.e. non‐macrophage cells) the uncleaved GlcCer, in GlcCer‐ase deficiency, is transferred to other cell compartments, where it may be processed and even accumulated to various degrees. The consequence of the abnormal extralysosomal load may differ according to the cell type and compartment targeted and may be influenced by genetically determined factors, by a number of acquired conditions, including the current metabolic situation. The sequelae of the uncleaved GlcCer extralysosomal transfer may range from probably innocent or positive stimulatory, to the much more serious, in which it interferes with a variety of cell functions, and in extreme cases, can lead to cell death. This alternative processing of uncleaved GlcCer may help to explain tissue alterations seen in GD that have, so far, resisted explanation based simply on the presence of GCs. Paralysosomal alternative processing may thus go a long way towards filling a long‐standing gap in the understanding of the molecular pathology of the disorder. The impact of this alternative process will most likely be inversely proportional to the level of residual GlcCer‐ase activity. Lysosomal sequestration of GlcCer in these cells is either absent or in those exceptional cases where it does occur, it is exceptional and rudimentary. It is suggested that paralysosomal alternative processing of uncleaved GlcCer is the main target for enzyme replacement therapy. The mechanism responsible for GlcCer transfer remains to be elucidated. It may also help in explaining the so far unclear origin of glucosylsphingosine (GlcSph) and define the mutual relation between these two processes.

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“…39 Myocardial involvement is often sub-clinical (preclinical phase of the cardiac phenotype), and circumstances such as pregnancy may favor the clinical onset of the cardiac phenotype. 40 …”

Section: Myocardial Involvementmentioning

confidence: 99%

Molecular Basis and Clinical Management of Gaucher Disease

2013

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Gaucher disease (GD) type I is an autosomal recessive disease caused by a genetic deficiency of lysosomal β-glucocerebrosidase that leads to accumulation of undergraded substrate glucocerebroside and other glycolipids, thus causing damage in different organs. GBA is the only gene in which mutations are known to cause GD. Nearly 300 mutations have been identified in GD patients, including frame-shift mutations, point mutations, deletions, insertions, splice site mutations and recombinants. The variety of phenotypes associated to GD shows imperfect correlation with mutations. GD encompasses a spectrum of clinical findings from a perinatal lethal form to an asymptomatic form. However the classification of GD by clinical subtype is still useful in describing the wide range of clinical findings and broad variability in presentation. Three major clinical types are delineated: type I (chronic nonneuropathic), type II (acute neuropathic), and type III (chronic neuropathic). Patients with type I GD present with visceromegaly, hematological complications, and bone disease. Cardiac and pulmonary complications are rare. Type I GD adult patients have elevated risk of malignancies, Parkinson’s disease or Parkinsonism. Neuropathic forms of GD are rare and clinically ranging from lethal perinatal form to very mild form limited to abnormalities of horizontal ocular saccades. Diagnosis of acid β-glucosylceramidase relies on enzyme activity in peripheral blood leukocytes or skin fibroblasts and/or identification of GBA mutations. Enzyme replacement therapy is an effective treatment for non-neuropathic GD. Substrate inhibitor is the alternative therapy for some patients with GD is miglustat, iminosugar inhibitor of glucocerebroside synthase

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Gaucher's disease with myocardial involvement in pregnancy

Cited by 21 publications

References 5 publications

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

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

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Molecular Basis and Clinical Management of Gaucher Disease

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