Is early detection of late-onset Pompe disease a pneumologist's affair? A lesson from an Italian screening study.
Acute respiratory failure
Diagnosis
Late-onset Pompe disease
Noninvasive ventilation
Respiratory high dependency care unit
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
04 03 2019
04 03 2019
Historique:
received:
12
11
2018
accepted:
21
02
2019
entrez:
6
3
2019
pubmed:
6
3
2019
medline:
8
10
2019
Statut:
epublish
Résumé
Late-onset Pompe disease (LOPD) is a recessive disease caused by α-glucosidase (GAA) deficiency, leading to progressive muscle weakness and/or respiratory failure in children and adults. Respiratory derangement can be the first indication of LOPD, but the diagnosis may be difficult for pneumologists. We hypothesize that assessing the GAA activity in suspected patients by a dried blood spot (DBS) may help the diagnosis of LOPD in the pneumological setting. We performed a multicenter DBS survey of patients with suspected LOPD according to a predefined clinical algorithm. From February 2015 to December 2017, 140 patients (57 ± 16 yrs., 80 males) were recruited in 19 Italian pneumological units. The DBS test was performed by a drop of blood collected on absorbent paper. Patients with GAA activity < 2.6 μmol/L/h were considered positive. A second DBS test was performed in the patients positive to the first assay. Patients testing positive at the re-test underwent a skeletal muscle biopsy to determine the GAA enzymatic activity. 75 recruited subjects had outpatient access, 65 subjects were admitted for an acute respiratory failure episode. Two patients tested positive in both the first and second DBS test (1.4% prevalence), and the LOPD diagnosis was confirmed through histology, with patients demonstrating a deficient GAA muscle activity (3.6 and 9.1 pmol/min/mg). A further five subjects were positive in the first DBS test but were not confirmed at re-test. The two positive cases were both diagnosed after hospitalization for acute respiratory failure and need of noninvasive ventilation. Most of the recruited patients had reduced maximal respiratory pressures (MIP 50 ± 27% and MEP 55 ± 27% predicted), restrictive pattern (FEV DBS GAA activity test may be a powerful screening tool among pneumologists, particularly in the acute setting. A simple clinical algorithm may aid in the selection of patients on which to administer the DBS test.
Sections du résumé
BACKGROUND
Late-onset Pompe disease (LOPD) is a recessive disease caused by α-glucosidase (GAA) deficiency, leading to progressive muscle weakness and/or respiratory failure in children and adults. Respiratory derangement can be the first indication of LOPD, but the diagnosis may be difficult for pneumologists. We hypothesize that assessing the GAA activity in suspected patients by a dried blood spot (DBS) may help the diagnosis of LOPD in the pneumological setting.
POPULATION AND METHODS
We performed a multicenter DBS survey of patients with suspected LOPD according to a predefined clinical algorithm. From February 2015 to December 2017, 140 patients (57 ± 16 yrs., 80 males) were recruited in 19 Italian pneumological units. The DBS test was performed by a drop of blood collected on absorbent paper. Patients with GAA activity < 2.6 μmol/L/h were considered positive. A second DBS test was performed in the patients positive to the first assay. Patients testing positive at the re-test underwent a skeletal muscle biopsy to determine the GAA enzymatic activity.
RESULTS
75 recruited subjects had outpatient access, 65 subjects were admitted for an acute respiratory failure episode. Two patients tested positive in both the first and second DBS test (1.4% prevalence), and the LOPD diagnosis was confirmed through histology, with patients demonstrating a deficient GAA muscle activity (3.6 and 9.1 pmol/min/mg). A further five subjects were positive in the first DBS test but were not confirmed at re-test. The two positive cases were both diagnosed after hospitalization for acute respiratory failure and need of noninvasive ventilation. Most of the recruited patients had reduced maximal respiratory pressures (MIP 50 ± 27% and MEP 55 ± 27% predicted), restrictive pattern (FEV
CONCLUSIONS
DBS GAA activity test may be a powerful screening tool among pneumologists, particularly in the acute setting. A simple clinical algorithm may aid in the selection of patients on which to administer the DBS test.
Identifiants
pubmed: 30832705
doi: 10.1186/s13023-019-1037-1
pii: 10.1186/s13023-019-1037-1
pmc: PMC6399888
doi:
Substances chimiques
alpha-Glucosidases
EC 3.2.1.20
Types de publication
Letter
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
62Subventions
Organisme : Genzyme (US)
ID : Unresctricted grant
Pays : International
Investigateurs
Alessio Mattei
(A)
Fausto De Michele
(F)
Luca Triolo
(L)
Giuseppe Culla
(G)
Pieraldo Canessa
(P)
Giuseppe Girbino
(G)
Mirco Lusuardi
(M)
Enrico Perretta
(E)
Claudio De Michelis
(C)
Teresa Renda
(T)
Références
Multidiscip Respir Med. 2018 Sep 1;13:32
pubmed: 30186604
Curr Mol Med. 2002 Mar;2(2):145-66
pubmed: 11949932
Mol Genet Metab. 2017 Mar;120(3):163-172
pubmed: 28185884
Genet Med. 2006 May;8(5):267-88
pubmed: 16702877
N Engl J Med. 2010 Apr 15;362(15):1396-406
pubmed: 20393176
Genet Med. 2006 May;8(5):302-6
pubmed: 16702880
J Neurol Neurosurg Psychiatry. 1984 May;47(5):549-52
pubmed: 6429285
J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):5-11
pubmed: 25783438
Respir Med. 2013 Aug;107(8):1124-32
pubmed: 23587901
J Neurol. 2017 Apr;264(4):621-630
pubmed: 27372449
Muscle Nerve. 2012 Mar;45(3):319-33
pubmed: 22173792
Brain. 2005 Mar;128(Pt 3):671-7
pubmed: 15659425
Mol Genet Metab. 2016 Sep;119(1-2):115-23
pubmed: 27473031
Neuromuscul Disord. 2007 Oct;17(9-10):698-706
pubmed: 17643989
Am J Med Genet A. 2013 Oct;161A(10):2431-43
pubmed: 23997011
Acta Myol. 2013 Oct;32(2):82-4
pubmed: 24399863
Respir Med. 2009 Apr;103(4):477-84
pubmed: 19131232
J Neurol. 2005 Aug;252(8):875-84
pubmed: 16133732
Muscle Nerve. 2009 Jul;40(1):149-60
pubmed: 19533647
Respir Care. 2011 Aug;56(8):1100-7
pubmed: 21496373