Propionic acidemia: neonatal versus selective metabolic screening
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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.
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.
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.
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.
Body mass index
Standard deviation score
Selective metabolic screening
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.
- 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
- Dayton CM (1970) The design of educational experiments. McGraw Hill, New YorkGoogle Scholar
- 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
- 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
- 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
- Illing S, Classen M (2006) Klinikleitfaden Pädiatrie, 7th edn. Urban und Fischer Verlag, MünchenGoogle Scholar
- 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
- 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
- Weiss RH (2006) Grundintelligenztest Skala 2 - Revision - (CFT 20-R). Göttingen, Hogrefe VerlagGoogle Scholar