Pompe disease clinical and laboratory diagnostic features
Background. Analysis of Pompe disease (PD) clinical features in children in order to determine its main clinical and laboratory characteristics based on the results of laboratory and instrumental studies that allow to select such patients into the screening group for enzymatic diagnosis in dried blood spots was the objective of this study. Materials and methods. In a period from 2002 to 2016, 522 children with PD suspicion were examined in the Center of Orphan Diseases of National Children’s Specialized Hospital “Ohmatdyt”. There were 282 boys and 240 girls aged from 4 months to 13 years. Results. According to electroneuromyography results and mutations in SMN gene revealing, spinal muscular atrophy was diagnosed in 98 (19 %) patients, Duchenne primary muscular dystrophy — in 70 (13 %). 71 (13.6 %) patients had different forms of hereditary neuropathy. In 38 (7.2 %) cases, the dominant type of disease inheritance was revealed, later we did not provide laboratory tests in those patients in order to confirm the PD diagnosis. Thus, 245 (47 %) patients were included into the selective (screening) group for enzymatic diagnosis using dried blood spot. In these patients, a heterogeneous clinical picture of the disease was noted: muscle weakness due to myopathic syndrome in combination with cardiomyopathy, delay in physical development, hyperCKemia. Twenty five patients aged 2 to 8 months besides myopathic syndrome had elevated levels of alanine aminotransferase and aspartate aminotransferase, creatine phosphokinase (more than 220 U/l), lactate dehydrogenase (more than 250 U/l), left ventricular hypertrophic cardiomyopathy; also in 10 patients, hepatomegaly and cardiopulmonary failure were revealed. Based on enzymatic tests, PD diagnosis (infantile form) was established in 5 patients (in 3 cases — classical form, in 2 cases — atypical). The clinical picture was heterogeneous, however, in all cases, slow increase in body weight, delay of static and kinetic skills forming were noted. Three patients receive enzyme replacement therapy. This allowed to prevent early death, and in one case, it was almost possible to restore independent walking. Conclusions. PD in children is characterized by different system failure and various clinical forms, in specific treatment absence, PD leads to patients’ early death. The PD main manifestations in children are hypertrophic cardiomyopathy, myopathic syndrome in combination with a specific biochemical phenotype. Enzymatic diagnosis in dried blood spots in the group of selective screening will increase the effectiveness of PD early diagnosis and treatment in children.
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Kishnani PS, Beckemeyer AA, Mendelsohn NJ. The new era of Pompe disease: advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management. Am J Med Genet C Semin Med Genet. 2012 Feb 15;160C(1):1-7. doi: 10.1002/ajmg.c.31324.
Lévesque S, Auray-Blais C, Gravel E, et al. Diagnosis of late-onset Pompe disease and other muscle disorders by next-generation sequencing. Orphanet J Rare Dis. 2016 Jan 25;11:8. doi: 10.1186/s13023-016-0390-6.
Yang CF, Liu HC, Hsu TR, et al. A large-scale nationwide newborn screening program for Pompe disease in Taiwan: towards effective diagnosis and treatment. Am J Med Genet A. 2014 Jan;164A(1):54-61. doi: 10.1002/ajmg.a.36197.
Pompe JC. Over idiopatische hypertrophie van het hart. Ned Tijdshr Geneeskd. 1932;76:304. (in Dutch).
Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D. Infantile-onset pompe disease natural history study G: a retrospective,multinational, multicenter study on the natural history of infantile-onset pompe disease. J Pediatr. 2006 May;148(5):671-676. doi: 10.1016/j.jpeds.2005.11.033.
Gungor D, de Vries JM, Hop WC, et al. Survival and associated factors in 268 adults with pompe disese prior to treatment with enzame replacement therapy. Orphanet J Rare Dis. 2011 Jun 1;6:34. doi: 10.1186/1750-1172-6-34.
Winchester B, Bali D, Bodamer OA, et al. Methods for a prompt and reliable laboratory diagnosis of Pompe disease: report from an international consensus meeting. Mol Genet Metab. 2008;93(3):275-81. doi:10.1016/j.ymgme.2007.09.006.
Lukacs Z, Nieves Cobos P, Mengel E, et al. Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes-possibility for newborn screening. J Inherit Metab Dis. 2010;33(1):43-50. doi:10.1007/s10545-009-9003-z.
Kishnani PS, Corzo D, Leslie ND, et al. Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res. 2009;66:329-35. doi:10.1203/PDR.0b013e3181b24e94.
Gasparоttо N, Tоmanіn R, Frіgо AC, et al. Rapіd dіagnоstіc testіng prоcedures fоr lysоsоmal stоrage dіsоrders: alpha-glucоsіdase and beta-galactоsіdase assays оn drіed blооd spоts. Clіn Chіm Acta. 2009;402(1-2):38-41. doi:10.1016/j.cca.2008.12.006.
Chamоles NA, Blancо MB, Gaggіоlі D, Casentіnі C. Gaucher and Niemann-Pick diseases--enzymatic diagnosis in dried blood spots on filter paper: retrospective diagnoses in newborn-screening cards. Clіn Chіm Act. 2002;317:191-7. PMID: 11814475.
Kishnani PS, Amartino HM, Lindberg C, Miller TM, Wilson A, Keutzer J. Timing of diagnosis of patients with Pompe disease: data from the Pompe registry. Am J Med Genet A. 2013;161A(10):2431-43. doi:10.1002/ajmg.a.36110.
Herzog A, Hartung R, Reuser AJ, et al. 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. Orphanet J Rare Dis. 2012;7:35. doi:10.1186/1750-1172-7-35.
Lam CW, Yuen YP, Chan KY, Tong SF, Lai CK, Chow TC, Lee KC, Chan YW, Martiniuk F. Juvenile-onset glycogen storage disease type II with novel mutations in acid alpha-glucosidase gene. Neurology. 2003;60(4):715-7. PMID:12601120.
Pittis MG, Donnarumma M, Montalvo AL, et al. Molecular and functional characterization of eight novel GAA mutations in Italian infants with Pompe disease. Hum Mutat. 2008;29(6):E27-36. doi:10.1002/humu.20753.
Kroos M, Pomponio RJ, van Vliet L, et al. Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Hum Mutat. 2008;29(6):E13-26. doi:10.1002/humu.20745.
Hermans MM, van Leenen D, Kroos MA, et al. Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II. Hum Mutat. 2004;23(1):47-56. doi:10.1002/humu.10286.
Gutiérrez-Rivas E, Bautista J, Vílchez JJ, et al. 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. Neuromuscular Disorders. 2015; 25(7):548-53. doi:10.1016/j.nmd.2015.04.008.
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