Newborn Screening Programmes in Europe, Arguments and Efforts Regarding Harmonisation: Focus on Organic Acidurias

Hörster, Friederike; Kölker, Stefan; Loeber, J.G.; Cornel, Martina C.; Hoffmann, Georg F.; Burgard, Peter

doi:10.1007/8904_2016_537

Cited by 20 publications

(22 citation statements)

References 25 publications

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“…Despite potential benefits of NBS for PA and MMACBL [ 1 , 25 ], these disorders are currently screened for in only few European countries (Austria, Belgium, Denmark, Hungary, Iceland, Portugal and Spain) [ 4 , 26 ]. This is in part attributable to relatively high false-positive rates if NBS for these disorders is based solely on C3 results [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders

et al. 2017

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Background and aimsIncreased propionylcarnitine levels in newborn screening are indicative for a group of potentially severe disorders including propionic acidemia (PA), methylmalonic acidemias and combined remethylation disorders (MMACBL). This alteration is relatively non-specific, resulting in the necessity of confirmation and differential diagnosis in subsequent tests. Thus, we aimed to develop a multiplex approach for concurrent determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid from the same dried blood spot (DBS) as in primary screening (second-tier test). We also set out to validate the method using newborn and follow-up samples of patients with confirmed PA or MMACBL.MethodsThe assay was developed using liquid chromatography–tandem mass spectrometry and clinically validated with retrospective analysis of DBS samples from PA or MMACBL patients.ResultsReliable determination of all three analytes in DBSs was achieved following simple and fast (<20 min) sample preparation without laborious derivatization or any additional pipetting steps. The method clearly distinguished the pathological and normal samples and differentiated between PA and MMACBL in all stored newborn specimens. Methylcitric acid was elevated in all PA samples; 3-hydroxypropionic acid was also high in most cases. Methylmalonic acid was increased in all MMACBL specimens; mostly together with methylcitric acid.ConclusionsA liquid chromatography–tandem mass spectrometry assay allowing simultaneous determination of the biomarkers 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in DBSs has been developed. The assay can use the same specimen as in primary screening (second-tier test) which may reduce the need for repeated blood sampling. The presented preliminary findings suggest that this method can reliably differentiate patients with PA and MMACBL in newborn screening. The validated assay is being evaluated prospectively in a pilot project for extension of the German newborn screening panel (‟Newborn screening 2020”; Newborn Screening Center, University Hospital Heidelberg).

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Section: Discussionmentioning

confidence: 99%

Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders

et al. 2017

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“…IVA has been included in newborn screening programmes in an increasing number of countries (Loeber et al 2012;Horster et al 2017) allowing pre-symptomatic diagnosis for LO-type IVA patients, but is likely to also prevent neonatal decompensation in the majority of EO-type IVA patients (Heringer et al 2016). Presymptomatically diagnosed and treated individuals often remain asymptomatic until adolescence/adulthood.…”

Section: Managementmentioning

confidence: 99%

“…GA1 has been included into newborn screening programmes in many countries (Loeber et al 2012;Horster et al 2017). Early diagnosis is the prerequisite of effective treatment and favourable outcome.…”

Section: Managementmentioning

confidence: 99%

Organic acidurias in adults: late complications and management

Tuncel

Boy

Morath

et al. 2018

J of Inher Metab Disea

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Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids ("organic acids") and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threatening acute metabolic crises and acute multi-organ failure. Tandem mass spectrometry-based newborn screening programmes, in particular for isovaleric aciduria and glutaric aciduria type 1, have significantly reduced diagnostic delay. Dietary treatment with low protein intake or reduced intake of the precursor amino acid(s), carnitine supplementation, cofactor treatment (in responsive patients) and nonadsorbable antibiotics is commonly used for maintenance treatment. Emergency treatment options with high carbohydrate/glucose intake, pharmacological and extracorporeal detoxification of accumulating toxic metabolites for intensified therapy during threatening episodes exist. Diagnostic and therapeutic measures have improved survival and overall outcome in individuals with OADs. However, it has become increasingly evident that the manifestation of late disease complications cannot be reliably predicted and prevented. Conventional metabolic treatment often fails to prevent irreversible organ dysfunction with increasing age, even if patients are considered to be "metabolically stable". This has challenged our understanding of OADs and has elicited the discussion on optimized therapy, including (early) organ transplantation, and long-term care.

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“…A diagnosis before the first symptomatic phase, feasible through newborn screening (NBS), could theoretically prevent the neurological damage . However, the majority of patients is symptomatic well before NBS results can be available, limiting the potential gain . Four studies described the potential additional value of NBS, but each with limited sample sizes and follow‐up time, resulting in controversy about the potential effectiveness of NBS for PA and MMA.…”

Section: Introductionmentioning

confidence: 99%

Retrospective evaluation of the Dutch pre‐newborn screening cohort for propionic acidemia and isolated methylmalonic acidemia: What to aim, expect, and evaluate from newborn screening?

Haijes

Molema

Langeveld

et al. 2019

J of Inher Metab Disea

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Evidence for effectiveness of newborn screening (NBS) for propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is scarce. Prior to implementation in the Netherlands, we aim to estimate the expected health gain of NBS for PA and MMA. In this national retrospective cohort study, the clinical Abbreviations: AMD, acute metabolic decompensation; AO, adverse outcome; BMD, bone mineral density; EO, early onset; LO, late onset; MMA, methylmalonic acidemia; NBS, newborn screening; PA, propionic acidemia; PY, patient year; WHO, World Health Organisation. Hanneke A. Haijes and Femke Molema contributed equally to this study; Monique Williams and Peter M. van Hasselt contributed equally to this study.

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Newborn Screening Programmes in Europe, Arguments and Efforts Regarding Harmonisation: Focus on Organic Acidurias

Cited by 20 publications

References 25 publications

Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders

Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders

Organic acidurias in adults: late complications and management

Retrospective evaluation of the Dutch pre‐newborn screening cohort for propionic acidemia and isolated methylmalonic acidemia: What to aim, expect, and evaluate from newborn screening?

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