Download PDF
Neuropediatrics 2018; 49(06): 363-368
DOI: 10.1055/s-0038-1661415
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Neurological Sequelae due to Inborn Metabolic Diseases in Pediatric Refugees: Challenges in Treating the Untreated

Katharina A. Schiergens
1   Department of Inborn Errors of Metabolism, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Michael Staudigl
1   Department of Inborn Errors of Metabolism, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Ingo Borggraefe
2   Department of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany
,
Esther M. Maier
1   Department of Inborn Errors of Metabolism, Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany
› Author Affiliations
Further Information

Publication History

18 January 2018

17 May 2018

Publication Date:
28 June 2018 (online)

    Permissions and Reprints

Abstract

In the 2015 mass migration from Syria and neighboring countries, Germany received an unprecedented number of 4,76,649 asylum applications. As many of the refugees arrived in Southern Germany via the Austrian border, the city of Munich was faced with the majority of Germany's inflow of war refugees and their complex health issues. Among the refugees were a high number of children. Their main health issues were infectious diseases and surgical procedures due to trauma, but we also encountered complex chronic diseases. This report describes clinical history, signs and symptoms, diagnostics, and treatment of six pediatric patients with untreated inborn errors of metabolism (IEM): phenylketonuria, biotinidase deficiency, HMG-CoA lyase deficiency, mucopolysaccharidosis type II, and mucopolysaccharidosis type VI. Since early diagnosis and treatment is essential in IEM, both delayed diagnosis and inadequate therapy in refugee children may lead to significant brain injury, organ damage, and even death. Severe neurological sequelae in both phenylketonuria and HMG-CoA lyase deficiency could have been prevented by newborn screening. Screening programs are necessary to improve the prognoses for refugee children. European Union governments and involved health care systems should pursue early diagnosis and treatment in pediatric refugees regarding IEM to prevent neurological long-term sequelae.

Keywords

inborn errors of metabolism - neurological sequelae - refugee medicine - newborn screening - phenylketonuria - biotinidase deficiency

Financial Support

No funding was received for the present study.


 

  • References

  • 1 Nicolai T, Fuchs O, von Mutius E. Caring for the wave of refugees in Munich. N Engl J Med 2015; 373 (17) 1593-1595
    CrossrefPubMedGoogle Scholar
  • 2 Alberer M, Wendeborn M, Löscher T, Seilmaier M. Erkrankungen bei Flüchtlingen und Asylbewerbern: Daten von drei verschiedenen medizinischen Einrichtungen im Raum München aus den Jahren 2014 und 2015 (in German). Dtsch Med Wochenschr 2016; 141 (01) e8-e15
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Pfortmueller CA, Schwetlick M, Mueller T, Lehmann B, Exadaktylos AK. Adult asylum seekers from the Middle East including Syria in Central Europe: what are their health care problems?. PLoS One 2016; 11 (02) e0148196
    CrossrefPubMedGoogle Scholar
  • 4 Calam R. Public health implications and risks for children and families resettled after exposure to armed conflict and displacement. Scand J Public Health 2017; 45 (03) 209-211
    CrossrefPubMedGoogle Scholar
  • 5 Refugees UNRWA, (UNRWA) itNE. The Annual Report of the Department of Health 2010. Available at: https://www.unrwa.org/userfiles/2011052062220.pdf . Accessed June 20, 2018
    PubMedGoogle Scholar
  • 6 Fingerhut R, Röschinger W, Muntau AC. , et al. Hepatic carnitine palmitoyltransferase I deficiency: acylcarnitine profiles in blood spots are highly specific. Clin Chem 2001; 47 (10) 1763-1768
    CrossrefPubMedGoogle Scholar
  • 7 Chace DH, Kalas TA, Naylor EW. Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem 2003; 49 (11) 1797-1817
    CrossrefPubMedGoogle Scholar
  • 8 Hoffmann G, Aramaki S, Blum-Hoffmann E, Nyhan WL, Sweetman L. Quantitative analysis for organic acids in biological samples: batch isolation followed by gas chromatographic-mass spectrometric analysis. Clin Chem 1989; 35 (04) 587-595
    CrossrefPubMedGoogle Scholar
  • 9 Castelli F, Sulis G. Migration and infectious diseases. Clin Microbiol Infect 2017; 23 (05) 283-289
    CrossrefPubMedGoogle Scholar
  • 10 Hoch M, Wieser A, Löscher T. , et al. Louse-borne relapsing fever (Borrelia recurrentis) diagnosed in 15 refugees from northeast Africa: epidemiology and preventive control measures, Bavaria, Germany, July to October 2015. Euro Surveill 2015;20(42)
    PubMedGoogle Scholar
  • 11 Duramaz A, Bilgili MG, Bayram B, Ziroğlu N, Bayrak A, Avkan MC. Orthopedic trauma surgery and hospital cost analysis in refugees; the effect of the Syrian civil War. Int Orthop 2017; 41 (05) 877-884
    CrossrefPubMedGoogle Scholar
  • 12 Therrell BL, Padilla CD, Loeber JG. , et al. Current status of newborn screening worldwide: 2015. Semin Perinatol 2015; 39 (03) 171-187
    Google Scholar
  • 13 American College of Medical Genetics/American Society of Human Genetics Test and Technology Transfer Committee Working Group. Tandem mass spectrometry in newborn screening. Genet Med 2000; 2 (04) 267-269
    PubMedGoogle Scholar
  • 14 Guthrie R, Susi A. A Simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 1963; 32: 338-343
    Google Scholar
  • 15 Palermo L, Geberhiwot T, MacDonald A, Limback E, Hall SK, Romani C. Cognitive outcomes in early-treated adults with phenylketonuria (PKU): a comprehensive picture across domains. Neuropsychology 2017; 31 (03) 255-267
    CrossrefPubMedGoogle Scholar
  • 16 Brosco JP, Paul DB. The political history of PKU: reflections on 50 years of newborn screening. Pediatrics 2013; 132 (06) 987-989
    CrossrefPubMedGoogle Scholar
  • 17 Wolf B. Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening. Genet Med 2017; 19 (04) 396-402
    PubMedGoogle Scholar
  • 18 Bittles AH. A community genetics perspective on consanguineous marriage. Community Genet 2008; 11 (06) 324-330
    PubMedGoogle Scholar
  • 19 Teebi AS, El-Shanti HI. Consanguinity: implications for practice, research, and policy. Lancet 2006; 367 (9515): 970-971
    CrossrefPubMedGoogle Scholar
  • 20 Kanaan ZM, Mahfouz R, Tamim H. The prevalence of consanguineous marriages in an underserved area in Lebanon and its association with congenital anomalies. Genet Test 2008; 12 (03) 367-372
    CrossrefPubMedGoogle Scholar
  • 21 Golbahar J, Al-Jishi EA, Altayab DD, Carreon E, Bakhiet M, Alkhayyat H. Selective newborn screening of inborn errors of amino acids, organic acids and fatty acids metabolism in the Kingdom of Bahrain. Mol Genet Metab 2013; 110 (1-2): 98-101
    CrossrefPubMedGoogle Scholar
  • 22 Al Riyami S, Al Maney M, Joshi SN, Bayoumi R. Detection of inborn errors of metabolism using tandem mass spectrometry among high-risk Omani patients. Oman Med J 2012; 27 (06) 482-485
    CrossrefPubMedGoogle Scholar
  • 23 da Silva EM, Strufaldi MW, Andriolo RB, Silva LA. Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome). Cochrane Database Syst Rev 2016; 2: CD008185
    PubMedGoogle Scholar
  • 24 Noh H, Lee JI. Current and potential therapeutic strategies for mucopolysaccharidoses. J Clin Pharm Ther 2014; 39 (03) 215-224
    CrossrefPubMedGoogle Scholar
  • 25 Colón C, Alvarez JV, Castaño C. , et al. A selective screening program for the early detection of mucopolysaccharidosis: results of the FIND project - a 2-year follow-up study. Medicine (Baltimore) 2017; 96 (19) e6887
    PubMedGoogle Scholar
  • 26 Golda A, Jurecka A, Opoka-Winiarska V, Tylki-Szymańska A. Mucopolysaccharidosis type VI: a cardiologist's guide to diagnosis and treatment. Int J Cardiol 2013; 167 (01) 1-10
    CrossrefPubMedGoogle Scholar
  • 27 Burton BK, Giugliani R. Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr 2012; 171 (04) 631-639
    CrossrefPubMedGoogle Scholar
  • 28 Wyatt K, Henley W, Anderson L. , et al. The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders. Health Technol Assess 2012; 16 (39) 1-543
    PubMedGoogle Scholar
  • 29 Muenzer J, Bodamer O, Burton B. , et al. The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. Eur J Pediatr 2012; 171 (01) 181-188
    CrossrefPubMedGoogle Scholar
  • 30 Das AM, Lagler F, Beck M, Scarpa M, Lampe C. Lysosomale Speichererkrankungen: Herausforderungen bei der sektorübergreifenden, multiprofessionellen Patientenversorgung mit Enzymersatztherapie (in German). Klin Padiatr 2017; 229 (03) 168-174
    Article in Thieme ConnectPubMedGoogle Scholar