'Classical' organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry.

Division of Metabolism, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, I-00165, Rome, Italy.
Journal of Inherited Metabolic Disease (Impact Factor: 4.14). 04/2006; 29(2-3):383-9. DOI: 10.1007/s10545-006-0278-z
Source: PubMed

ABSTRACT 'Classical organic acidurias' comprise isovaleric aciduria, propionic aciduria and methylmalonic aciduria. Available data from the literature suggest that the use of 'new' therapeutic strategies has improved survival but has not modified neurodevelopment. Progressive neurocognitive deterioration is almost invariably present in propionic and methylmalonic acidurias, while large-scale studies on the long-term outcome of patients with isovaleric aciduria are still lacking. In order to answer to some of the questions suggested by Wilson and Jungner in 1968 about the criteria of disease screening, we compared the natural history of patients with 'classical' organic acidurias diagnosed on clinical bases to those diagnosed through neonatal mass screening using tandem mass spectrometry. Decreased early mortality, less severe symptoms at diagnosis, and more favourable short-term neurodevelopmental outcome were recorded in patients identified through expanded newborn screening. The short duration of follow-up so far does not allow us to draw final conclusions about the effects of newborn screening on long-term outcome. The evaluation of the effect of neonatal screening on the detection rate of these three diseases showed that the incidence of isovaleric aciduria was significantly higher in the screening population than in clinically detected cases, with no changes for propionic and methylmalonic acidurias. Further multicentre longitudinal studies are needed to assess the usefulness of expanded newborn screening for 'classical' organic acidurias and to better understand the clinical spectrum of these diseases. This paper describes the long-term outcome and the impact of expanded newborn screening on the so-called 'classical' organic acidurias (propionic aciduria, methylmalonic aciduria and isovaleric aciduria).

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    ABSTRACT: Background In recent years it has become clear that newborn screening (NBS) programs using tandem mass spectrometry identify “patients” with “classical” inborn errors of metabolism who are asymptomatic. This observation raises issues regarding medicalization of ‘non-diseases’, potentially unnecessary treatment and unnecessary anxiety to parents. Aims To identify possible markers that may assist in predicting the need for treatment of infants with ‘classical’ organic acidaemias (OA) and urea cycle disorders (UCD) diagnosed through NBS. Methods Medical records of all patients with classical OA and UCD detected through the Victorian NBS program from February 2002 to January 2014, or diagnosed clinically between 1990- January 2002 were retrospectively reviewed. Results Neonatal presentation did not always predict the need for on-going strict treatment. Blood concentrations of amino acids and acyl-carnitines and the changes thereof in follow-up samples correlated with severity in citrullinaemia-I, possibly isovaleric acidaemia but not in argininosuccinic aciduria or propionic acidaemia. Some specific mutations correlate with ‘attenuated’ citrullinaemia-I. Gender may affect clinical outcome in propionic-acidaemia. Conclusions Changes in blood concentration of certain metabolites (amino acids, acyl-carnitines) in the first weeks of life may be predictive of the need for treatment in some disorders but not in others. Mutation analysis may be predictive in some disorders but whether or not this should be considered as second tier testing in NBS should be discussed separately.
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    ABSTRACT: Propionic acidemia is an organic aciduria produced by the deficiency of propionyl CoA-carboxylase, producing a ketotic hyperglycinemia and recurrent metabolic imbalance. Although rare, it is the more common inborn error of the metabolic disorders. This is a case of late-onset progressive type of this inherited disease, with clinical evolution towards mental retardation and delayed neurological development with extrapyramidalism abnormalities. The report of the case illustrates the clinical of ketoacidosis with hyperammonemia, its final diagnosis and treatment. Key words: Propionic acidemia, organic aciduria.
    Rev Mex Pediatr. 01/2006; 73:230-2..
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