title: 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.
abstract: We aimed to screen for Pompe disease in patients with unclassified limb-girdle muscular dystrophy (LGMD) or asymptomatic hyperCKemia using dried blood spot (DBS) assays. Subsequently, we aimed to calculate the diagnostic delay between initial symptom presentation and the diagnosis. A prospective, multicenter, observational study was conducted in 348 patients: 146 with unclassified LGMD and 202 with asymptomatic or paucisymptomatic hyperCKemia. We quantified levels of acid alpha-glucosidase (GAA) from dried blood spots analyzed fluorometrically. The test was positive in 20 patients, and Pompe disease was confirmed by genetic testing in 16. Undiagnosed Pompe disease was detected in 7.5% of patients with LGMD and in 2.5% of patients with persistent, idiopathic elevation of serum creatine kinase. The c.-32-13 T > G mutation was found most commonly. The diagnostic delay was 15 years on average. In conclusion, DBS tests are useful and reliable screening tools for Pompe disease. We recommend the dried blood spot test to be included in the diagnostic work-up of patients with unclassified myopathies with proximal weakness and/or hyperCKemia of unknown cause and, when positive, to define the diagnosis, it will have to be confirmed by biochemical and/or molecular genetic analysis.
authors.affiliation: Department of Neurology, Neuromuscular Unit, 12 de Octubre University Hospital, Madrid, Spain. Electronic address: doctoregr@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Gutiérrez-Rivas
authors.affiliation: Department of Neurology, Sagrado Corazón Clinic, Seville, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Bautista
authors.affiliation: La Fe University and Polytechnic Hospital, Valencia, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Vílchez
authors.affiliation: La Fe University and Polytechnic Hospital, Valencia, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Muelas
authors.affiliation: Neuromuscular Pathology Unit, Department of Neurology, Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Manera
authors.affiliation: Neuromuscular Pathology Unit, Department of Neurology, Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Illa
authors.affiliation: Neuropathology Institute IDIBELL, Bellvitge Hospital, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Martínez-Arroyo
authors.affiliation: Neuropathology Institute IDIBELL, Bellvitge Hospital, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Olivé
authors.affiliation: Department of Neurology, La Paz University Hospital, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Sanz
authors.affiliation: Department of Neurology, La Paz University Hospital, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Arpa
authors.affiliation: Department of Neurology, Donostia University Hospital, San Sebastián, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Fernández-Torrón
authors.affiliation: Department of Neurology, Donostia University Hospital, San Sebastián, Spain.
authors.forename: A
authors.initials: A
authors.lastname: López de Munáin
authors.affiliation: Clínical Biochemistry Section, Virgen del Rocío University Hospital, Seville, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Jiménez
authors.affiliation: Molecular Oncogenetic Unit, Institute of Medical and Molecular Genetics, La Paz University Hospital, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Solera
authors.affiliation: Institute of Clinical Chemistry, Department of Pediatrics, Hamburg University Medical Center, Hamburg, Germany.
authors.forename: Z
authors.initials: Z
authors.lastname: Lukacs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003402:Creatine Kinase / Q000097:blood*; D057210:Delayed Diagnosis; D059788:Dried Blood Spot Testing; D005260:Female; D005820:Genetic Testing; D006009:Glycogen Storage Disease Type II / Q000097:blood* / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000097:blood* / Q000150:complications / Q000235:genetics; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000097:blood* / Q000150:complications / Q000201:enzymology; D009154:Mutation; D011446:Prospective Studies; D055815:Young Adult; D000520:alpha-Glucosidases / Q000097:blood
chemical_list: D003402:Creatine Kinase; D000520:alpha-Glucosidases
keywords: Creatine kinase; Dried blood spots; Enzyme replacement therapy; GAA deficiency; Glycogen storage disease; Myopathy