Journal of Inherited Metabolic Disease

, Volume 35, Issue 1, pp 41–49 | Cite as

Propionic acidemia: neonatal versus selective metabolic screening

  • S. C. Grünert
  • S. Müllerleile
  • L. de Silva
  • M. Barth
  • M. Walter
  • K. Walter
  • T. Meissner
  • M. Lindner
  • R. Ensenauer
  • R. Santer
  • O. A. Bodamer
  • M. R. Baumgartner
  • M. Brunner-Krainz
  • D. Karall
  • C. Haase
  • I. Knerr
  • T. Marquardt
  • J. B. Hennermann
  • R. Steinfeld
  • S. Beblo
  • H. G. Koch
  • V. Konstantopoulou
  • S. Scholl-Bürgi
  • A. van Teeffelen-Heithoff
  • T. Suormala
  • W. Sperl
  • J. P. Kraus
  • A. Superti-Furga
  • K. O. Schwab
  • J. O. Sass
Branched-Chain Amino Acids

Abstract

Background

Whereas propionic acidemia (PA) is a target disease of newborn screening (NBS) in many countries, it is not in others. Data on the benefit of NBS for PA are sparse.

Study design

Twenty PA patients diagnosed through NBS were compared to 35 patients diagnosed by selective metabolic screening (SMS) prompted by clinical findings, family history, or routine laboratory test results. Clinical and biochemical data of patients from 16 metabolic centers in Germany, Austria, and Switzerland were evaluated retrospectively. Additionally, assessment of the intelligent quotient (IQ) was performed. In a second step, the number of PA patients who have died within the past 20 years was estimated based on information provided by the participating metabolic centers.

Results

Patients diagnosed through NBS had neither a milder clinical course regarding the number of metabolic crises nor a better neurological outcome. Among NBS patients, 63% were already symptomatic at the time of diagnosis, and <10% of all patients remained asymptomatic. Among all PA patients, 76% were found to be at least mildly mentally retarded, with an IQ <69. IQ was negatively correlated with the number of metabolic decompensations, but not simply with the patients’ age. Physical development was also impaired in the majority of patients. Mortality rates tended to be lower in NBS patients compared with patients diagnosed by SMS.

Conclusion

Early diagnosis of PA through NBS seems to be associated with a lower mortality rate. However, no significant benefit could be shown for surviving patients with regard to their clinical course, including the number of metabolic crises, physical and neurocognitive development, and long-term complications.

Abbreviations

BMI

Body mass index

CFT

Culture-free test

IQ

Intelligence quotient

NBS

Newborn screening

PA

Propionic acidemia

PCC

Propionyl-CoA carboxylase

SDS

Standard deviation score

SMS

Selective metabolic screening

SON

Snijders-Omen Test

Notes

Acknowledgements

We are grateful to Milupa Metabolics GmbH & Co. KG, Friedrichsdorf, Germany, for financial support of this study and especially for the support of the Freiburg Workshop on Propionic Acidemia (16–18 October 2008). We also thank the Eva-Uth-Stiftung, Kehl, Germany, and the Müller-Fahnenberg-Stiftung, Freiburg, Germany, for financial support.

References

  1. American College of Medical Genetics Newborn Screening Expert Group (2006) Newborn screening: toward a uniform screening panel and system-executive summary. Pediatrics 117:S296–S307Google Scholar
  2. Baumgartner D, Scholl-Bürgi S, Sass JO et al (2007) Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia. J Pediatr 150:192–197PubMedCrossRefGoogle Scholar
  3. Bodamer OA, Hoffmann GF, Lindner M (2007) Expanded newborn screening in Europe 2007. J Inherit Metab Dis 30:439–444PubMedCrossRefGoogle Scholar
  4. Dayton CM (1970) The design of educational experiments. McGraw Hill, New YorkGoogle Scholar
  5. de Baulny HO, Benoist JF, Rigal O, Touati G, Rabier D (2005) Saudubray JM (2005) Methylmalonic and propionic acidaemias: management and outcome. J Inherit Metab Dis 28(3):415–423PubMedCrossRefGoogle Scholar
  6. Dionisi-Vici C, Deodato F, Röschinger W, Rhead W, Wilcken B (2006) 'Classical' organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis 29:383–389PubMedCrossRefGoogle Scholar
  7. Ensenauer R, Vockley J, Willard JM, Huey JC, Sass JO, Edland SD, Burton BK, Berry SA, Santer R, Grünert S, Koch HG, Marquardt I, Rinaldo P, Hahn S, Matern D (2004) A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. Am J Hum Genet 75:1136–1142PubMedCrossRefGoogle Scholar
  8. Fenton WA, Gravel WA, Rosenblatt DS (2001) Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Bases of Inherited Diseases. McGraw-Hill, New York, pp 2165–2193Google Scholar
  9. Illing S, Classen M (2006) Klinikleitfaden Pädiatrie, 7th edn. Urban und Fischer Verlag, MünchenGoogle Scholar
  10. Kölker S, Christensen E, Leonard JV et al (2007) Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I). J Inherit Metab Dis 30:5–22PubMedCrossRefGoogle Scholar
  11. Kraus JP, Spector E, Venezia S, Estes P, Chiang P-W, Creadon-Swindell G, Müllerleile S, de Silva L, Barth M, Walter M, Walter K, Meissner T, Lindner M, Ensenauer R, Santer R, Bodamer OA, Baumgartner MR, Brunner- Krainz M, Karall D, Haase C, Knerr I, Marquardt T, Hennermann JB, Steinfeld R, Beblo S, Koch HG, Konstantopoulou V, Scholl-Bürgi S, van Teeffelen-Heithoff A, Suormala T, Ugarte M, Sperl W, Superti-Furga A, Schwab KO, Grünert SC, Sass JO (2011) Mutation analysis in 54 propionic acidemia patients. J Inherit Metab Dis. doi:10.1007/s10545-011-9399-0
  12. Lehnert W, Sperl W, Suormala T, Baumgartner ER (1994) Propionic acidaemia: clinical, biochemical and therapeutic aspects. Experience in 30 patients. Eur J Pediatr 153:68–80CrossRefGoogle Scholar
  13. Nennstiel-Ratzel U, Arenz S, Maier E et al (2005) Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A > G identified by neonatal screening. Mol Genet Metab 85:157–159PubMedCrossRefGoogle Scholar
  14. North KN, Korson MS, Gopal YR (1995) Neonatal-onset propionic acidemia: neurologic and developmental profiles, and implications for management. J Pediatr 126:916–922PubMedCrossRefGoogle Scholar
  15. Rela M, Battula N, Madanur M (2007) Auxiliary liver transplantation for propionic acidemia: a 10-year follow-up. Am J Transplant 7:2200–2203PubMedCrossRefGoogle Scholar
  16. Sass JO, Hofmann M, Skladal D, Mayatepek E, Schwahn B, Sperl W (2004) Propionic acidemia revisited: a workshop report. Clin Pediatr 43:837–843CrossRefGoogle Scholar
  17. Surtees RAH, Matthews EE, Leonard JV (1992) Neurologic outcome of propionic acidemia. Pediatr Neurol 8:333–337PubMedCrossRefGoogle Scholar
  18. Tellegen PJ, Laros JA, Petermann F (2007) Snijders-Oomen Non-verbaler Intelligenztest von 2½ bis 7 Jahren (SON-R 2½ - 7). Testmanual mit deutscher Normierung und Validierung. Hogrefe Verlag, GöttingenGoogle Scholar
  19. Touati G, Valayannopoulos V, Mention K (2006) Methylmalonic and propionic acidurias: management without or with a few supplements of specific amino acid mixture. J Inherit Metab Dis 29:288–298PubMedCrossRefGoogle Scholar
  20. van der Meer SB, Poggi F, Spada M et al (1996) Clinical outcome and long-term management of 17 patients with propionic acidaemia. Eur J Pediatr 155:205–210PubMedCrossRefGoogle Scholar
  21. Weiss RH (2006) Grundintelligenztest Skala 2 - Revision - (CFT 20-R). Göttingen, Hogrefe VerlagGoogle Scholar
  22. Wilcken B (2010) Fatty acid oxidation disorders: outcome and long-term prognosis. J Inherit Metab Dis 33:501–506PubMedCrossRefGoogle Scholar
  23. Wilcken B, Haas M, Joy P et al (2007) Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet 369:37–42PubMedCrossRefGoogle Scholar
  24. Wolf B, Paulsen EP, Hsia YE (1979) Asymptomatic propionyl-CoA carboxylase deficiency in a 13-year-old girl. J Pediatr 95:563–565PubMedCrossRefGoogle Scholar
  25. Wolf B, Hsia YE, Sweetman L, Gravel R, Harris DJ, Nyhan WL (1981) Propionic acidemia: a clinical update. J Pediatr 99:835–846PubMedCrossRefGoogle Scholar
  26. Yorifuji T, Kawai M, Mamada M et al (2004) Living-donor liver transplantation for propionic acidaemia. J Inherit Metab Dis 27:205–210PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • S. C. Grünert
    • 1
  • S. Müllerleile
    • 2
  • L. de Silva
    • 2
  • M. Barth
    • 1
  • M. Walter
    • 2
  • K. Walter
    • 1
  • T. Meissner
    • 3
  • M. Lindner
    • 4
  • R. Ensenauer
    • 5
  • R. Santer
    • 6
  • O. A. Bodamer
    • 7
  • M. R. Baumgartner
    • 8
  • M. Brunner-Krainz
    • 9
  • D. Karall
    • 10
  • C. Haase
    • 11
  • I. Knerr
    • 12
  • T. Marquardt
    • 13
  • J. B. Hennermann
    • 14
  • R. Steinfeld
    • 15
  • S. Beblo
    • 16
  • H. G. Koch
    • 17
  • V. Konstantopoulou
    • 7
  • S. Scholl-Bürgi
    • 10
  • A. van Teeffelen-Heithoff
    • 13
  • T. Suormala
    • 18
  • W. Sperl
    • 19
  • J. P. Kraus
    • 20
  • A. Superti-Furga
    • 1
  • K. O. Schwab
    • 1
  • J. O. Sass
    • 2
  1. 1.Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum FreiburgFreiburgGermany
  2. 2.Labor für Klinische Biochemie und Stoffwechsel, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum FreiburgFreiburgGermany
  3. 3.Klinik für Allgemeine Pädiatrie, Universitätsklinikum DüsseldorfDüsseldorfGermany
  4. 4.Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum HeidelbergHeidelbergGermany
  5. 5.Research Center, Dr. von Hauner Children’s Hospital, Klinikum der Universität MünchenMünchenGermany
  6. 6.Universitätsklinikum Hamburg-Eppendorf, KinderklinikHamburgGermany
  7. 7.Allgemeine Pädiatrie, AKH, Medizinische Universität WienWienAustria
  8. 8.Stoffwechsel und Molekulare Pädiatrie, KinderspitalZürichSwitzerland
  9. 9.Universitätsklinikum für Kinder- und Jugendheilkunde, Medizinische Universität GrazGrazAustria
  10. 10.Universitätsklinik für Kinder- und Jugendheilkunde, Medizinische Universität InnsbruckInnsbruckAustria
  11. 11.Klinik für Kinder- und Jugendmedizin, Universitätsklinikum JenaJenaGermany
  12. 12.Universitätskinderklinik ErlangenErlangenGermany
  13. 13.Allgemeine Pädiatrie, Universitätskinderklinik MünsterMünsterGermany
  14. 14.Allgemeine Pädiatrie, Charité Universitätsmedizin BerlinBerlinGermany
  15. 15.Kinderklinik, Georg-August-Universität GöttingenGöttingenGermany
  16. 16.Universitätsklinikum für Kinder und JugendlicheLeipzigGermany
  17. 17.Klinik für Kinder- und JugendmedizinBraunschweigGermany
  18. 18.Kinderspital BaselBaselSwitzerland
  19. 19.Universitätsklinikum für Kinder- und Jugendheilkunde, Paracelsus Medizinische PrivatuniversitätSalzburgAustria
  20. 20.Department of PediatricsUniversity of ColoradoAuroraUSA

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