How to describe the clinical spectrum in Pompe disease?

Güngör, Deniz; Reuser, Arnold

doi:10.1002/ajmg.a.35662

Cited by 62 publications

(54 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The other patients had nonclassic or late-onset Pompe disease: group 2 comprised 13 patients with symptom onset before the age of 18 years (childhood onset), and group 3 comprised 95 patients with symptom onset after the age of 18 years (adult onset). 23 Diagnosis was confirmed by a deficiency of acid α-glucosidase GAA (was already abbreviated earlier in text) in leukocytes or fibroblasts and mutation analysis. The Medical Ethics Committee at Erasmus University Medical Center approved the study protocol.…”

Section: Study Populationmentioning

confidence: 96%

Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease

Wens

Schaaf

Michels

et al. 2016

Circ Cardiovasc Genet

View full text Add to dashboard Cite

Background— Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury. Methods and Results— In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values <14 ng/L). Cardiac troponin I levels were normal in all patients, whereas CK-myocardial band levels were increased in 59% of patients. cTnT levels correlated with CK levels in all 3 subgroups ( P <0.001). None of the abnormal ECGs recorded in 21 patients were indicative of acute myocardial infarction, and there were no differences in cTnT levels between patients with and without (n=90) abnormalities on ECG (median 28 ng/L in both groups). The median left ventricular mass index measured with echocardiography was normal in all the 3 subgroups. cTnT mRNA expression in skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue. Conclusions— Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions.

show abstract

Section: Study Populationmentioning

confidence: 96%

Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease

Wens

Schaaf

Michels

et al. 2016

Circ Cardiovasc Genet

View full text Add to dashboard Cite

show abstract

“…However, the continuum of phenotypes often defies categorization. Recently, the Pompe community accepted the following proposed nomenclature: (1) “classic infantile”, as described above; (2) “childhood” form with onset of symptoms from birth till adolescence without persisting and progressive cardiac hypertrophy; and (3) “adult” form with onset of symptoms from adolescence to late adulthood (Güngör and Reuser, 2013). …”

Section: Genetic Defects and Clinical Manifestationsmentioning

confidence: 99%

Pompe disease: from pathophysiology to therapy and back again

Lim¹,

Li²,

Raben³

2014

Front. Aging Neurosci.

160

182

View full text Add to dashboard Cite

Pompe disease is a lysosomal storage disorder in which acid alpha-glucosidase (GAA) is deficient or absent. Deficiency of this lysosomal enzyme results in progressive expansion of glycogen-filled lysosomes in multiple tissues, with cardiac and skeletal muscle being the most severely affected. The clinical spectrum ranges from fatal hypertrophic cardiomyopathy and skeletal muscle myopathy in infants to relatively attenuated forms, which manifest as a progressive myopathy without cardiac involvement. The currently available enzyme replacement therapy (ERT) proved to be successful in reversing cardiac but not skeletal muscle abnormalities. Although the overall understanding of the disease has progressed, the pathophysiology of muscle damage remains poorly understood. Lysosomal enlargement/rupture has long been considered a mechanism of relentless muscle damage in Pompe disease. In past years, it became clear that this simple view of the pathology is inadequate; the pathological cascade involves dysfunctional autophagy, a major lysosome-dependent intracellular degradative pathway. The autophagic process in Pompe skeletal muscle is affected at the termination stage—impaired autophagosomal-lysosomal fusion. Yet another abnormality in the diseased muscle is the accelerated production of large, unrelated to ageing, lipofuscin deposits—a marker of cellular oxidative damage and a sign of mitochondrial dysfunction. The massive autophagic buildup and lipofuscin inclusions appear to cause a greater effect on muscle architecture than the enlarged lysosomes outside the autophagic regions. Furthermore, the dysfunctional autophagy affects the trafficking of the replacement enzyme and interferes with its delivery to the lysosomes. Several new therapeutic approaches have been tested in Pompe mouse models: substrate reduction therapy, lysosomal exocytosis following the overexpression of transcription factor EB and a closely related but distinct factor E3, and genetic manipulation of autophagy.

show abstract

“…So far, with a few recent exceptions, neonatal screening has been restricted to childhood-onset disorders, where early detection and intervention or treatment can prevent irreversible health damage [8]. Current screening tests for Pompe disease not only detect the classic infantile form - lethal in the first years of life, when untreated – but also less severe cases, for which the age of onset might vary from infancy to adulthood [9]. Since the traditional focus of neonatal screening does not fit well with the potential outcome of this new kind of screening for broad-spectrum disorders, introduction of neonatal screening for Pompe disease would need to be carefully considered from all angles, and screening criteria might need rethinking [10,11].…”

Section: Introductionmentioning

confidence: 99%

Newborn screening for pompe disease? a qualitative study exploring professional views

Rigter

Reuser

et al. 2014

BMC Pediatr

View full text Add to dashboard Cite

BackgroundDevelopments in enzyme replacement therapy have kindled discussions on adding Pompe disease, characterized by progressive muscle weakness and wasting, to neonatal screening. Pompe disease does not fit traditional screening criteria as it is a broad-spectrum phenotype disorder that may occur in lethal form in early infancy or manifest in less severe forms from infancy to late adulthood. Current screening tests cannot differentiate between these forms. Normally, expanding screening is discussed among experts in advisory bodies. While advisory reports usually mention the procedures and outcome of deliberations, little is known of the importance attached to different arguments and the actual weighing processes involved. In this research we aim to explore the views of a wide range of relevant professionals to gain more insight into the process of weighing pros and cons of neonatal screening for Pompe disease, as an example of the dilemmas involved in screening for broad-spectrum phenotype disorders.MethodsWe conducted 24 semi-structured interviews with medical, lab, insurance and screening professionals, and executive staff of patient organisations. They were asked about their first reaction to neonatal screening for Pompe disease, after which benefits and harms and requirements for screening were explored in more detail.ResultsAdvantages included health gain by timely intervention, avoiding a diagnostic quest, having a reproductive choice and gaining more knowledge about the natural course and treatment. Being prepared was mentioned as an advantage for the later manifesting cases. Disadvantages included treatment costs and uncertainties about its effect, the timing of treatment in later manifesting cases, the psychological burden for the patient-in-waiting and the family. Also the downsides of having prior knowledge as well as having to consider a reproductive option were mentioned as disadvantages.ConclusionWhen weighing pros and cons, interviewees attach different importance to different arguments, based on personal and professional views. Professionals expect benefits from neonatal screening for Pompe disease, especially for early-onset cases. Some interviewees valued screening in later manifesting cases as well, while stressing the need for adequate support of pre-symptomatic patients and their families. Others considered the psychological burden and uncertainties regarding treatment as reasons not to screen.

show abstract

How to describe the clinical spectrum in Pompe disease?

Cited by 62 publications

References 2 publications

Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease

Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease

Pompe disease: from pathophysiology to therapy and back again

Newborn screening for pompe disease? a qualitative study exploring professional views

Contact Info

Product

Resources

About