scholarly journals Is early detection of late-onset Pompe disease a pneumologist’s affair? A lesson from an Italian screening study

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Marco Confalonieri ◽  
◽  
Michele Vitacca ◽  
Raffaele Scala ◽  
Mario Polverino ◽  
...  
Keyword(s):  
Early Detection ◽  
Pompe Disease ◽  
Late Onset ◽  
Screening Study

scholarly journals Prominent Respiratory Involvement Featured in High-Risk Screening for Late-Onset Pompe Disease in China

2021 ◽  
Author(s):  
Kexin Jiao ◽  
Jihong Dong ◽  
Sushan Luo ◽  
Liqiang Yu ◽  
Qing Ke ◽  
...  
Keyword(s):  
High Risk ◽  
Muscle Weakness ◽  
Respiratory Insufficiency ◽  
Pompe Disease ◽  
Late Onset ◽  
Final Diagnosis ◽  
High Risk Population ◽  
Multicenter Observational Study ◽  
Respiratory Involvement ◽  
Screening Study

Abstract Backgroud: 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 difficulty. A multicenter observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in high-risk population, using dried blood spot (DBS) as a main screening tool.Methods: 20 Chinese neuromuscular centers were involved in the early LOPD screening study. Inclusion criteria were: (1) age ≥1 years, (2) either one of a) persistent hyperCKemia; or b) muscle weakness of axial and/or limb-girdle muscles; or c) unexplained restrictive respiratory insufficiency. Enzymatic activity of acid α-glucosidase (GAA) was measured on DBS by tandem mass spectrometry (MS/MS) assay. For the final diagnosis genotype was assessed by next-generation sequencing.Result: In a 9-month period, we studied 492 cases: 26 positive samples (5.3%) were detected by DBS screening. Molecular studies finally confirmed LOPD diagnosis in 8 cases (1.6%). The GAA activities in individuals bearing pseudodeficiency alleles were well separated from those in LOPD patients by MS/MS assay. The median interval from the onset of symptoms to diagnosis was 5 years. Besides axial/proximal muscle weakness, all patients showed respiratory insufficiency with a mean forced vital capacity of predicted of 48%. The level of creatine kinase ranged from normal to no more than 5-fold of upper normal limit. LOPD with isolated hyperCKemia was not identified.Conclusions: This study confirms that DBS test is a reliable method for screening for LOPD. Respiratory insufficiency is earlier and more severe among Chinese LOPD patients. LOPD presented with paucisymptomatic hyperCKemia. Therefore, a prompt diagnosis is critical to prognosis.

Late onset Pompe Disease in India – Beyond the Caucasian phenotype

2021 ◽  
Author(s):  
Ratna Dua Puri ◽  
Nitika Setia ◽  
Vinu N ◽  
Sujatha Jagadeesh ◽  
Sheela Nampoothiri ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Late Onset

NEO1/NEO-EXT studies: Safety and exploratory efficacy of repeat avalglucosidase alfa dosing after up to 6 years in participants with late-onset pompe disease (LOPD)

2021 ◽  
Vol 132 (2) ◽  
pp. S34
Author(s):  
Mazen M. Dimachkie ◽  
Richard J. Barohn ◽  
Barry Byrne ◽  
Ozlem Goker-Alpan ◽  
Priya S. Kishnani ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Late Onset

scholarly journals Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

2021 ◽  
Vol 22 (7) ◽  
pp. 3625
Author(s):  
Filomena Napolitano ◽  
Giorgia Bruno ◽  
Chiara Terracciano ◽  
Giuseppina Franzese ◽  
Nicole Piera Palomba ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Rare Variants ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Respiratory Muscles ◽  
Autosomal Recessive Disorder ◽  
Compound Heterozygous ◽  
Enzyme Replacement ◽  
Whole Exome ◽  
Clinical Pictures

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.

Expanding the phenotype of late-onset pompe disease: Tongue weakness: A new clinical observation

2011 ◽  
Vol 44 (6) ◽  
pp. 897-901 ◽  
Author(s):  
Alberto Dubrovsky ◽  
Jose Corderi ◽  
Min Lin ◽  
Priya S. Kishnani ◽  
Harrison N. Jones
Keyword(s):  
Pompe Disease ◽  
Clinical Observation ◽  
Late Onset
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