Back to Search Start Over

The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by expanded newborn metabolic screening in Italy: the importance of an integrated diagnostic approach.

Authors :
Catanzano F
Ombrone D
Di Stefano C
Rossi A
Nosari N
Scolamiero E
Tandurella I
Frisso G
Parenti G
Ruoppolo M
Andria G
Salvatore F
Source :
Journal of inherited metabolic disease [J Inherit Metab Dis] 2010 Dec; Vol. 33 Suppl 3, pp. S91-4. Date of Electronic Publication: 2010 Feb 16.
Publication Year :
2010

Abstract

A pilot expanded newborn screening programme to detect inherited metabolic disorders by means of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) began in the Campania region, southern Italy, in 2007. By October 2009, >8,800 dried blood samples on filter paper from 11 hospitals had been screened. Within this screening programme, we identified a case of mitochondrial acetoacetyl-coenzyme A (CoA) thiolase deficiency [β-ketothiolase (β-KT) deficiency] by analysing the acylcarnitine profile from a dried blood spot with LC-MS/MS. Gas chromatography coupled with mass spectrometry analysis of urinary organic acids and LC-MS/MS analysis of urinary acylcarnitines were in line with this disorder. In fact, concentrations were well beyond the cut-off values of tiglyl carnitine, 3-hydroxybutyrylcarnitine and 2-methyl-3-hydroxybutyrylcarnitine, 2-methyl-3-hydroxybutyric acid and tiglyl glycine. The absence of 2-methylacetoacetic acid in urine may be attributed to: (i) the instability of this β-ketoacid because it undergoes spontaneous decarboxylation to 2-butanone, which is highly volatile and thus difficult to detect, and (ii) the good health of the patient in the first days of life. β-KT deficiency was subsequently diagnosed in the patient's older sister, who showed increased levels of the same metabolites but also small amounts of 2-methylacetoacetic acid, which is considered a key marker for β-KT diagnosis. Genomic analysis revealed mutation c.1189C >G in exon 12 of the ACAT1 gene, which results in a severe defect because of the p.H397D amino acid change in both alleles of both patients.

Details

Language :
English
ISSN :
1573-2665
Volume :
33 Suppl 3
Database :
MEDLINE
Journal :
Journal of inherited metabolic disease
Publication Type :
Academic Journal
Accession number :
20157782
Full Text :
https://doi.org/10.1007/s10545-009-9028-3