Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort

Gutiérrez-Rivas, Eduardo; Bautista, Juan; Vílchez, Juan J.; Muelas, Nuria; Díaz‐Manera, Jordi; Illa, Isabel; Martínez-Arroyo, Amaia; Olivé, Montse; Sanz, Iván; Arpa, Javier; Fernández‐Torrón, Roberto; Munáin, Adolfo López de; Jiménez, Luís; Solera, Jesús; Lukács, Zoltán

doi:10.1016/j.nmd.2015.04.008

Cited by 51 publications

(53 citation statements)

References 28 publications

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“…The introduction of enzyme replacement therapy with alglucosidase alpha has increased the general awareness of this disease [3], but diagnosis delay is significant and estimated to be around 7 years from signs/symptoms onset in LOPD 2 [7]. Although an accurate and early diagnosis of LOPD 2 is difficult to achieve, early treatment was reported to be associated to a better efficacy of the therapy [4].…”

Section: Pdmentioning

confidence: 99%

“…Estimated worldwide incidence of all forms of PD 1 is 1 in 40,000 live births [1,5], but several studies showed that incidence rate may vary among different ethnic populations, ranging from 1:14,000 in an African American population to 1:600,000 in a Portuguese population [7]. There are some data that permit estimate the prevalence of PD 1 in Caucasian to 1-2:100,000 [7].…”

Section: Pdmentioning

confidence: 99%

“…There are some data that permit estimate the prevalence of PD 1 in Caucasian to 1-2:100,000 [7]. It is known that PD 1 is very rare in Scandinavia [8].…”

Section: Pdmentioning

confidence: 99%

“…Screening for PD 1 in high risk populations using DBS 3 was already performed in some European populations (Table 2) both in neuromuscular and respiratory units [4][5][6][7][8][9][10][11]. Apart from one study that included only patients with asymptomatic or minimally symptomatic hyperCKemia (mild non-specific myalgia or mild fatigue) [4], the other cohorts included also cases of proximal weakness without a definitive diagnosis.…”

Section: Pdmentioning

confidence: 99%

“…DBS is increasingly recommended in the diagnostic work-up of patients with unclassified myopathies with proximal weakness as a useful tool to reach early diagnosis of PD 1 [7,10]. DBS 3 assay for PD 1 could also be considered in patients with asymptomatic or paucisymptomatic hyperCKemia as a simple instrument to exclude a treatable neuromuscular disorder.…”

Section: Pdmentioning

confidence: 99%

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Screening for Pompe disease in a Portuguese high risk population

D’Almeida

Conceição

Fineza

et al. 2017

Neuromuscular Disorders

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Pompe disease is a rare metabolic disorder with available enzymatic replacement therapy. Contrasting with the classic infantile form, the others subtypes have a heterogeneous presentation that makes an early and accurate diagnosis difficult. We conducted a prospective, multicenter, observational study to identify undiagnosed patients. During a one-year period, patients followed in Portuguese neuromuscular outpatient clinics with proximal muscle weakness affecting upper and/or lower limbs, hyperCKemia in two or more determinations or hypotonia and hyperCKemia, were screened for acid α-glucosidase deficiency by dried blood spots. Lysosomal acid-alpha-1,4-glucosidase activity was determined by tandem mass spectrometry and positive results were confirmed by molecular study. From the 99 patients screened, Pompe disease was confirmed in 4, with age of onset ranging from 2.5 to 48 years, all with limb girdle muscle weakness, corresponding to a frequency of 4% in our cohort and 4.9% of limb girdle muscle weakness. Screening for Pompe disease in high risk populations, using dried blood spots, was already performed in some European populations. Apart from two negative Scandinavian studies, positive cases were confirmed in 2.8-7.9% of patients presenting with limb girdle muscle weakness and in 0-2.5% with isolated hyperCKemia.

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Section: Pdmentioning

confidence: 99%

Section: Pdmentioning

confidence: 99%

“…There are some data that permit estimate the prevalence of PD 1 in Caucasian to 1-2:100,000 [7]. It is known that PD 1 is very rare in Scandinavia [8].…”

Section: Pdmentioning

confidence: 99%

Section: Pdmentioning

confidence: 99%

Section: Pdmentioning

confidence: 99%

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Screening for Pompe disease in a Portuguese high risk population

D’Almeida

Conceição

Fineza

et al. 2017

Neuromuscular Disorders

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Vacuolated PAS‐positive lymphocytes as an hallmark of Pompe disease and other myopathies related to impaired autophagy

Pascarella¹,

Terracciano

Farina

et al. 2018

Journal Cellular Physiology

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Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-α-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive, and specific test is crucial to early identify affected subjects. Number of lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72 consecutive adult patients with hyperckemia and/or muscle weakness, 13 genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring. GAA activity, measured on dried blood spot (DBS) in all patients inversely correlated with number of PAS-positive lymphocytes. More than 4 PAS-positive lymphocytes were found in 11 out of the 72 patients (6 new diagnosis of LOPD, 3 different glycogen storage myopathies, 1 glucose-6-phosphate dehydrogenase deficiency, 1 caveolinopathy), in all 13 LOPD patients and in the 13 LOPD offspring. These latter resulted to have all a single GAA mutation but low GAA levels. Immunostaining with the autophagy markers LC3 and p62 confirmed the autophagic nature of lymphocytes vacuoles. ROC curve assessment of PAS-positive lymphocytes disclosed 100% of sensitivity and 94% of specificity in recognizing both compound heterozygous and heterozygous GAA carriers. The other myopathies with more than 4 PAS-positive lymphocytes appeared to be all related to impaired autophagy, which seems to be responsible of PAS-positive vacuolated lymphocytes formation. Quantification of PAS-positive lymphocytes in blood films is useful to identify autophagic vacuolar myopathies and should be routinely used as first level test for Pompe disease.

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Prevalence, pathological mechanisms, and genetic basis of limb‐girdle muscular dystrophies: A review

Taghizadeh

Rezaee

Barreto

et al. 2018

Journal Cellular Physiology

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Limb‐girdle muscular dystrophies (LGMDs) are a highly heterogeneous group of neuromuscular disorders that are associated with weakness and wasting of muscles in legs and arms. Signs and symptoms may begin at any age and usually worsen by time. LGMDs are autosomal disorders with different types and their prevalence is not the same in different areas. New technologies such as next‐generation sequencing can accelerate their diagnosis. Several important pathological mechanisms that are involved in the pathology of the LGMD include abnormalities in dystrophin–glycoprotein complex, the sarcomere, glycosylation of dystroglycan, vesicle and molecular trafficking, signal transduction pathways, and nuclear functions. Here, we provide a comprehensive review that integrates LGMD clinical manifestations, prevalence, and some pathological mechanisms involved in LGMDs.

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Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort

Cited by 51 publications

References 28 publications

Screening for Pompe disease in a Portuguese high risk population

Screening for Pompe disease in a Portuguese high risk population

Vacuolated PAS‐positive lymphocytes as an hallmark of Pompe disease and other myopathies related to impaired autophagy

Prevalence, pathological mechanisms, and genetic basis of limb‐girdle muscular dystrophies: A review

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