The right ventricle in Fabry disease

Kampmann, Christoph; Baehner, FA; Whybra, Catharina; Bajbouj, M; Baron, Karin; Knuf, M; Wiethoff, Christiane M.; Trübel, H.; Beck, Michael

doi:10.1080/08035320510028049

Cited by 39 publications

(21 citation statements)

References 11 publications

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“…Its aetiology may be a reduction in stroke volume and cardiac output, especially at stress induced by LV hypertrophy, increased left atrial pressure due to poor diastolic function, or both. Right ventricular involvement has also been suggested to have a role in this cascade (Kampmann et al 2005). Mean exercise capacity was 60% of the reference value, which is at the same level as observed earlier in Fabry disease (Bierer et al 2006).…”

Section: Efficiency Of Ert Regarding the Severity Of Fabry Diseasesupporting

confidence: 78%

Twenty‐four‐month α‐galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters

Koskenvuo

Hartiala

Nuutila

et al. 2008

J of Inher Metab Disea

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Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available. It has been reported to improve clinical symptoms and quality of life. However, limited and controversial data on its efficacy to cardiac involvement have been published. Nine patients (5 male) with Fabry disease were included in an open-label prospective follow-up study of 24-month ERT. Comprehensive cardiovascular evaluation was performed by MRI, stress echocardiography and quality of life assessment. Plasma globotriaosylceramide decreased from 6.2 to 1.4 microg/ml during ERT (p<0.05). The only other measured parameters that changed significantly were resting heart rate that decreased from 79 to 67 bpm (p<0.01) and end-systolic volume that decreased by 12.4 ml (p<0.05). The other parameters consisting of quality of life, self-estimated cardiovascular condition, diastolic function, exercise capacity, ECG parameters, ejection fraction and ventricular mass did not change. ERT has only minimal effect on symptoms and cardiovascular morphology and function in Fabry disease. Therefore, effective conventional medical therapy is still of major importance in Fabry disease. Larger ERT studies are warranted, especially in women, to solve current open questions, such as the age at which ERT should be started, optimal dosage and intervals between infusions. Furthermore, longer follow-up studies are needed to assess the effects of ERT on prognosis.

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Section: Efficiency Of Ert Regarding the Severity Of Fabry Diseasesupporting

confidence: 78%

Twenty‐four‐month α‐galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters

Koskenvuo

Hartiala

Nuutila

et al. 2008

J of Inher Metab Disea

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“…RV involvement is common in FD and ultimately progresses to severe diastolic RV dysfunction. These findings might explain why patients with preserved left ventricule (LV) function can develop clinical features such as reduced exercise capacity, organomegaly and lymphoedema [94]. …”

Section: Reviewmentioning

confidence: 99%

Fabry disease

Germain

2010

Orphanet J Rare Dis

1,049

1,230

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Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones.

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“…На ранних стадиях преоб-ладает диастолическая дисфункция, в дальнейшем часто возникает снижение систолической функции, левожелудочковая недостаточность [66]. Возможна гипертрофия правого желудочка с развитием систо-лической и диастолической дисфункции [67]. Акку-муляция гликосфинголипидов в гладких мышечных РОССИЙСКИЙ ВЕСТНИК ПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 2, 2016 ROSSIYSKIY VESTNIK PERINATOLOGII I PEDIATRII, 2,2016 клетках и эндотелии сосудистой стенки приводит к значительному снижению коронарного кровотока и миокардиального резерва [68].…”

Section: обзоры литературыunclassified

Cardiomyopathies in children with inborn errors of metabolism

Леонтьева¹,

Николаева²

2016

Ross. vestn. perinatol. pediatr.

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The right ventricle in Fabry disease

Cited by 39 publications

References 11 publications

Twenty‐four‐month α‐galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters

Twenty‐four‐month α‐galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters

Fabry disease

Cardiomyopathies in children with inborn errors of metabolism

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