Unusual Echocardiographic Pattern in Gaucher&amp;rsquo;s Disease

Platzker, Yaakov; Fisman, Enrique Z.; Pines, A; Kellermann, Jan J.

doi:10.1159/000173855

Cited by 9 publications

(8 citation statements)

References 5 publications

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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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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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“…27 Table 2 describes typical cardiac pictures of patients with Gaucher disease (red flags). [28][29][30][31][32][33][34][35][36][37] The presence of one or more red flags could signal possible disease.…”

Section: Prevalence Severity and Time Of Onsetmentioning

confidence: 99%

“…38 Emblematic cases, such as a 17-year old girl with pseudohypertrophy and calcification of both left and right ventricles 28 and a patients with adult type I Gaucher with left ventricular thickening and an extended area of apical akinesis have been described. 29 A dilated/hypokinetic phenotype represents probably the evolution of the pseudo hypertrophy or the initial inflammatory response to Gaucher's cells infiltration. The enzyme replacement therapy has been reported to be beneficial for the recovery of left ventricular function.…”

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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“…3 Clinically overt, direct involvement of the heart is uncommon. [4][5][6][7][8][9][10][11][12] Cases of pericardial disease, with hemorrhagic or constrictive pericarditis and pericardial calcification have been observed. 4 Valvular heart disease (mitral and aortic fibrocalcification and stenosis, often resembling rheumatic disease) has also been associated with GD, 5,6 especially with the subtype of the subacute neuropathic form (Type IIIc).…”

mentioning

confidence: 99%

“…[8][9][10][11] Left ventricular (LV) hypertrophy and diastolic dysfunction at Doppler echocardiography have been described in individual cases of patients affected by GD1. 12,13 However, no study has analyzed yet LV geometry and function in a series of consecutive GD patients. Accordingly, the aim of the present study was to investigate whether subclinical LV myocardial abnormalities can be detected in a group of patients with GD1.…”

mentioning

confidence: 99%

Left Ventricular Diastolic Dysfunction in Type I Gaucher Disease: An Echo Doppler Study

et al. 2014

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Type I Gaucher disease (GD1) is an autosomal recessive lysosomal storage disease characterized by multiorgan damage. Left ventricular (LV) involvement has been rarely reported. Accordingly, the aim of the study was to evaluate LV geometry and function in a series of patients with GD1. Eighteen patients with GD1, 18 age- and sex-matched normal controls, and 18 age- and sex-matched hypertensive patients (HTN) were compared by standard echo Doppler examination. LV mass index, relative wall thickness and ejection fraction, transmitral E/A ratio, E velocity deceleration time (DT), atrial filling fraction (AFF = time-velocity integral of A velocity/time-velocity integral of total diastole × 100), E/e' ratio, and left atrial volume index were determined. Nine GD1 patients also exhibited arterial hypertension. The intergroup difference of LV mass index and relative wall thickness was not significant. Transmitral E/A ratio was lower in HTN than in normal controls and GD1 (P < 0.05). GD1 exhibited longer DT than NC and HTN (P = 0.009). AFF was higher in GD1 and HTN compared to NC (P = 0.034). After adjustment for heart rate, GD1 was associated with longer DT (P < 0.001) and greater AFF (P = 0.036), while HTN was associated only with AFF (P = 0.013). No interaction was found between GD1 and HTN. In conclusion, GD1 is associated with subclinical LV diastolic dysfunction, which is independent of the coexistence of arterial hypertension. Subclinical LV impaired relaxation in the context of myocardial infiltrative damage could be the mechanism underlying these alterations.

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Unusual Echocardiographic Pattern in Gaucher’s Disease

Cited by 9 publications

References 5 publications

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

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

Left Ventricular Diastolic Dysfunction in Type I Gaucher Disease: An Echo Doppler Study

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