'Classical' organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry.
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.Molecular Genetics and Metabolism 09/2014; · 2.83 Impact Factor
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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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ABSTRACT: Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of¿~¿1: 50,000 and PA of¿~¿1:100¿000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA and cardiomyopathy mainly in PA. Except for vitamin B12 responsive forms of MMA the outcome remains poor despite the existence of apparently effective therapy with a low protein diet and carnitine. This may be related to under recognition and delayed diagnosis due to nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity.These guidelines aim to provide a trans-European consensus to guide practitioners, set standards of care and to help to raise awareness. To achieve these goals, the guidelines were developed using the SIGN methodology by having professionals on MMA/PA across twelve European countries and the U.S. gather all the existing evidence, score it according to the SIGN evidence level system and make a series of conclusive statements supported by an associated level of evidence. Although the degree of evidence rarely exceeds level C (evidence from non-analytical studies like case reports and series), the guideline should provide a firm and critical basis to guide practice on both acute and chronic presentations, and to address diagnosis, management, monitoring, outcomes, and psychosocial and ethical issues. Furthermore, these guidelines highlight gaps in knowledge that must be filled by future research. We consider that these guidelines will help to harmonize practice, set common standards and spread good practices, with a positive impact on the outcomes of MMA/PA patients.Orphanet Journal of Rare Diseases 09/2014; 9(1):130. · 3.96 Impact Factor