Pompe disease clinical and laboratory diagnosis optimization among other hereditary neuromuscular diseases (literature review, own observations)

N.O. Pichkur


Background. Analysis of Pompe disease (PD) clinical features, determination of myopathic syndromes main characteristics according to the results of clinical, laboratory and instrumental studies allowing to select such patients into screening group for PD enzyme diagnosis. Materials and methods. In 2002–2016, in the Center of orphan diseases a comprehensive clinical and laboratory study was conducted in 614 patients with clinical manifestations of hereditary neuromuscular disease. There were 314 male and 300 female patients aged 2 months to 34 years. Results. In 78 patients, myopathy with dominant inheritance was detected, further laboratory tests on PD haven’t been conducted. In 98 patients, spinal muscular atrophy was diagnosed, in 70 — Duchenne primary muscular dystrophy, in 123 — different forms of hereditary neurosensory neuropathy. Screening group for PD detection using enzyme diagnosis method consisted of 421 patients, who had unclassified myopathic syndromes characterized by a heterogeneous clinical picture, in particular, general muscle weakness without hypertrophy. Electroneuromyography was performed in 187 patients: all of them showed patterns of myopathic process without signs of denervation and spontaneous activity (fibrillation or myotonic phenomena). In 25 patients aged 2 to 18 months, increased levels of creatine phosphokinase, lactate dehydrogenase, and liver transaminases were detected. Moreover, in 10 patients, hypertrophic cardiomyopathy, respiratory distress were revealed. According to enzyme diagnosis results, PD in dried blood spot was diagnosed in 5 patients. Conclusions. Main characteristics for the selective search group on PD were determined, in which enzyme diagnosis in dried blood spot was effective. Such characteristics are: autosomal recessive type of disease inheritance; wide age intervals; increased levels of creatine phosphokinase, hepatic transaminases; myopathic lesion localization (predominantly in muscles of proximal parts of the extremities and body), characteristic electroneuromyography changes; hypertrophic cardiomyopathy.


Pompe disease; enzyme diagnosis; dried blood spot method


Козлова С.И., Семенова Е.А. Наследственные синдромы и медико-генетическое консультирование. — СПб., 1997. — 316 с.

Неврология раннего детского возраста / Под ред. проф. С.К. Евтушенко. — К., 2016. — 285 с.

van Adel B.A. Metabolic myopathies: update 2009 / van B.A. Adel,

M.A. Tarnopolsky // J. Clin. Neuromuscul. Dis. — 2009. — Vol. 10, № 3. — P. 97-121.

Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease / P.S. Kishnani, D. Corzo,

N.D. Leslie, D. Gruskin, A. van der Ploeg, J.P. Clancy, R. Parini, G. Morin, M. Beck, M.S. Bauer, M. Jokic, C.E. Tsai, B.W. Tsai,

C. Morgan, T. O’Meara, S. Richards, E.C. Tsao, H. Mandel //

Pediatr. Res. — 2009. — Vol. 66. — P. 329-335.

Pompe disease diagnosis and management guideline / P.S. Kishnani, R.D. Steiner, D. Bali, K. Berger, B.J. Byrne,

L.E. Case, J.F. Crowley, S. Downs, R.R. Howell, R.M. Kravitz, J. Mackey,

D. Marsden, A.M. Martins, D.S. Millington, M. Nicolino, G. O’Grady, M.C. Patterson, D.M. Rapoport, A. Slonim, C.T. Spencer, C.J. Tifft, M.S. Watson // Genet. Med. — 2006. — Vol. 8. — P. 267-288.

van der Ploeg A.T. Pompe’s disease / A.T. van der Ploeg,

A.J. Reuser // Lancet. — 2008. — Vol. 372, № 9646. — P. 1342-1353.

Yin-Hsiu Chien. Pompe disease: early diagnosis and early treatment make a difference / Yin-Hsiu Chien, Wuh-Liang Hwu, Ni-Chung Lee // Pediatr. Neonatol. — 2013. — Vol. 54, № 4. — P. 219-227.

Disease severity in children and adults with Pompe disease related to age and disease duration / M.L. Hagemans, L.P. Winkel, W.C. Hop, A.J. Reuser, P.A. van Doorn, A.T. van der Ploeg // Neuro­logy. — 2005. — Vol. 64, № 12. — P. 2139-2141.

Pompe J.-C. Over idiopatische hypertrophie van het hart /

J.-C. Pompe // Ned. Tijdshr. Geneeskd. — 1932. — Vol. 76. — P. 304.

Facial-muscle weakness, speech disorders and dysphagia are common in patients with classic infantile Pompe disease treated with enzyme therapy / C.M. van Gelder, C.I. van Capelle, B.J. Ebbink, I. Moor-van Nugteren, J.M. van den Hout, M.M. Hakkesteegt, P.A. van Doorn, I.F. de Coo, A.J. Reuser, H.H. de Gier, A.T. van der Ploeg // J. Inherit. Metab. Dis. — 2012. — Vol. 35, № 3. — P. 505-511.

Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy / D. Gungor, J.M. de Vries, W.C. Hop, A.J. Reuser, P.A. van Doorn, A.T. van der Ploeg, M.L. Hagemans // Orphanet. J. Rare Dis. — 2011. — Vol. 6. — P. 34.

Dilative arteriopathy and basilar artery dolichoectasia complicating late onset Pompe disease / P. Laforet, M. Nicolino, D. Orlikowski, C. Callaud, N. Pelligrini, R. Froissart, T. Petitjean, I. Maire, H. Chabriat, L. Hadrane, D. Annane, B. Eymard // Neurology. — 2008. — Vol. 70. — P. 2063-2066.

Methods for a prompt and reliable laboratory diagnosis of Pompe disease: report from an international consensus meeting / B. Winchester, D. Bali, O.A. Bodamer, C. Caillaud, E. Christensen, A. Cooper, E. Cupler, M. Deschauer, K. Fumic, M. Jackson, P. Kishnani, L. Lacerda, J. Ledvinova, A. Lugowska, Z. Lukacs, I. Maire, H. Mandel, E. Mengel, W. Muller-Felber, M. Piraud, A. Reuser,

T. Rupar, I. Sinigerska, M. Szlago, F. Verheijen, O.P. van Diggelen, B. Wuyts, E. Zakharova, J. Keutzer // Mol. Genet. Metab. — 2008. — Vol. 93, № 3. — P. 275-281.

Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes-possibility for newborn screening / Z. Lukacs, P. Nieves Cobos, E. Mengel, R. Hartung, M. Beck, M. Deschauer, A. Keil, R. Santer //

J. Inherit. Metab. Dis. — 2010. — Vol. 33, № 1. — P. 43-50.

Diagnosis of late-onset Pompe disease and other muscle disorders by next-generation sequencing / S. Lévesque, C. Auray-Blais, E. Gravel, M. Boutin, L. Dempsey-Nunez, P.-E. Jacques, S. Chenier, S. Larue, M.-F. Rioux, W. Al-Hertani, A. Nadeau, J. Mathieu,

B. Maranda, V. Désilets, P.J. Waters, J. Keutzer, S. Austin, P. Kishnani // Orphanet. J. Rare Dis. — 2016. — Vol. 11. — P. 8-9.

A large-scale nationwide newborn screening program for Pompe disease in Taiwan: towards effective diagnosis and treatment / C.-F. Yang, H.-C. Liu, T.-R. Hsu, F.-C. Tsai, S.-F. Chiang,

C.-C. Chiang, H.C. Ho, C.J. Lai, T.F. Yang, S.Y. Chuang, C.Y. Lin, D.M. Niu // Am. J. Med. Genet. A. — 2014. — Vol. 164, № 1. — P. 54-61.

Rapіd dіagnоstіc testіng prоcedures fоr lysоsоmal stоrage dіsоrders: alpha-glucоsіdase and betagalactоsіdase assays оn drіed blооd spоts / N. Gasparоttо, R. Tоmanіn, A.C. Frіgо, G. Nііzawa, E. Pasquіnі, M. Blancо, M.A. Dоnatі, J. Keutzer, F. Zacchellо,

M. Scarpa // Clіn. Chіm. Acta. — 2009. — Vol. 402, № 1–2. — P. 38-41.

Timing of diagnosis of patients with Pompe disease: data from the Pompe registry / P.S. Kishnani, H.M. Amartino, C. Lindberg,

T.M. Miller, A. Wilson, J. Keutzer // Am. J. Med. Genet. A. — 2013. — Vol. 161A, № 10. — P. 2431-2443.

Childhood Pompe disease: clinical spectrum and genotype in 31 patients / C.I. van Capelle, J.C. van der Meijden, J.M.P. van den Hout, J. Jaeken, M. Baethmann, T. Voit, M.A. Kroos, T.G.J. Derks, M.E. Rubio-Gozalbo, M.A. Willemsen, R.H. Lachmann, E. Mengel, H. Michelakakis, J.C. de Jongste, A.J.J. Reuser, A.T. van der Ploeg // Orphanet. J. Rare Dis. — 2016. — Vol. 11, № 1. — P. 65.

Phenotypical variation within 22 families with Pompe disease / S.C.A. Wens, C.M. van Gelder, M.E. Kruijshaar, J.M. de Vries, N.A. van der Beek, A.J.J. Reuser, P.A. van Doorn, A.T. van der Ploeg, E. Brusse // Orphanet. J. Rare Dis. — 2013. — Vol. 8. — P. 182.

A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations / A. Herzog, R. Hartung, A.J.J. Reuser, P. Hermanns, H. Runz, N. Karabul, S. Gökce,

J. Pohlenz, C. Kampmann, C. Lampe, M. Beck, E. Mengel // Orphanet. J. Rare Dis. — 2012. — Vol. 7. — P. 35.

Mitochondrial disease criteria: diagnostic applications in children / E. Morava, L. van den Heuvel, F. Hol, M.C. de Vries, M. Hogeveen, R.J. Rodenburgand, J.A.M. Smeitink // Neurology. — 2006. — Vol. 67, № 10. — P. 1823-1826.

Kishnani P.S. The new era of Pompe disease: advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management / P.S. Kishnani, A.A. Beckemeyer, N.J. Mendelsohn // Am. J. Med. Genet. C: Semin. Med. Genet. — 2012. — Vol. 160C, № 1. — P. 1-7.

EFNS guidelines on the diagnostic approach to pauci- or asymptomatic hyperCKemia / T. Kyriakides, C. Angelini, J. Schaefer,

S. Sacconi, G. Siciliano, J.J. Vilchez, D. Hilton-Jones // Eur. J. Neurol. — 2010. — Vol. 17, № 6. — P. 767-773.

Leslie N. Glycogen storage disease type II (Pompe disease). Gene Reviews / N. Leslie, B.T. Tinkle // Neuromuscular Disord. — 2015. — Vol. 25, № 7. — P. 548-553.

Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: of Spanish cohort / E. Gutiérrez-Rivas, J. Bautista, J.J. Vílchez, N. Muelas, J. Díaz-Manera, I. Illa,

A. Martínez-Arroyo, M. Olivé, I. Sanz, J. Arpa, R. Fernández-Torrón, A. López de Munáin, L. Jiménez, J. Solera, Z. Lukacs // Neuromuscar Disord. — 2015. — Vol. 25, № 7. — P. 548-553.

Vissing J. Diagnosis of Pompe disease: muscle biopsy vs blood-based assays / J. Vissing, Z. Lukacs, V. Straub // JAMA Neurol. — 2013. — Vol. 70, № 7. — P. 923-927.

Late-onset Pompe disease is prevalent in unclassified limb-girdle muscular dystrophies / N. Preisler, Z. Lukacs, L. Vinge,

K.L. Madsen, E. Husu, R.S. Hansen, M. Duno, H. Andersen,

M. Laub, J. Vissing // Mol. Genet. Metab. — 2013. — Vol. 110,

№ 3. — P. 287-289.


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