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

Division of Metabolism, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, I-00165, Rome, Italy.
Journal of Inherited Metabolic Disease (Impact Factor: 3.37). 04/2006; 29(2-3):383-9. DOI: 10.1007/s10545-006-0278-z
Source: PubMed


'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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    • "Patients typically presents at the age of 1-month to 1-year with varied presentations of symptoms ranging from poor feeding, vomiting, dehydration, shock, hypoglycemia, hyperammonemia and hyperglycemias with high anion gap (AG) metabolic acidosisif left untreated can lead coma or even death [7] [8] [9]. Organs involvement in methylmalonic acidemia includes central nervous system (CNS), bone marrow and kidneys. "

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    • "Patients with organic acidurias frequently present with acute symptoms early in life [5]. The range of clinical manifestations is diverse, involving multiple body systems with a predominance of the central nervous system [6] [7]. Clinical and laboratory findings that suggest an organic acidemia include acidosis, ketosis, hyperammonemia, abnormal liver function tests, hypoglycemia, and neutropenia [8]. "

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    • "It can present either in the neonatal period as an acute episode of fulminant metabolic acidosis, which can lead to coma or death, or it can manifest later as the "chronic intermittent form," which is associated with developmental delays, with or without recurrent acidotic episodes during periods of stress, and infections1-4). The inability to detect this disorder early may lead to severe neurocognitive dysfunction, psychomotor retardation, or death3,4). Here, we report a child whose diagnosis was delayed until 2 years of age. IVA was confirmed by genetic testing, which revealed the two novel mutations. "
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    ABSTRACT: Isovaleric aciduria (IVA) is caused by an autosomal recessive deficiency of isovaleryl-CoA dehydrogenase (IVD). IVA presents either in the neonatal period as an acute episode of fulminant metabolic acidosis, which may lead to coma or death, or later as a "chronic intermittent form" that is associated with developmental delays, with or without recurrent acidotic episodes during periods of stress, such as infections. Here, we report the case of a 2-year old boy with IVA who presented with the chronic intermittent form. He was admitted to Asan Medical Center Children's Hospital with recurrent vomiting. Metabolic acidosis, hyperammonemia, elevated serum lactate and isovalerylcarnitine levels, and markedly increased urine isovalerylglycine concentration were noted. Sequence analysis of the IVD gene in the patient revealed the novel compound mutations-a missense mutation, c.986T>C (p.Met329Thr) and a frameshift mutation, c.1083del (p.Ile361fs*11). Following stabilization during the acute phase, the patient has remained in a stable condition on a low-leucine diet.
    Korean Journal of Pediatrics 08/2013; 56(8):351-4. DOI:10.3345/kjp.2013.56.8.351
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