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The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by expanded newborn metabolic screening in Italy: the importance of an integrated diagnostic approach.
J Inherit Metab Dis 2010; 33 Suppl 3:S91-4JI

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.

Authors+Show Affiliations

CEINGE-Biotecnologie Avanzate, Napoli, Dipartimento di Scienze Biologiche ed Ambientali, Università del Sannio, Benevento, Naples, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20157782

Citation

Catanzano, Francesca, et al. "The First Case of Mitochondrial acetoacetyl-CoA Thiolase Deficiency Identified By Expanded Newborn Metabolic Screening in Italy: the Importance of an Integrated Diagnostic Approach." Journal of Inherited Metabolic Disease, vol. 33 Suppl 3, 2010, pp. S91-4.
Catanzano F, Ombrone D, Di Stefano C, et al. The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by expanded newborn metabolic screening in Italy: the importance of an integrated diagnostic approach. J Inherit Metab Dis. 2010;33 Suppl 3:S91-4.
Catanzano, F., Ombrone, D., Di Stefano, C., Rossi, A., Nosari, N., Scolamiero, E., ... Salvatore, F. (2010). The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by expanded newborn metabolic screening in Italy: the importance of an integrated diagnostic approach. Journal of Inherited Metabolic Disease, 33 Suppl 3, pp. S91-4. doi:10.1007/s10545-009-9028-3.
Catanzano F, et al. The First Case of Mitochondrial acetoacetyl-CoA Thiolase Deficiency Identified By Expanded Newborn Metabolic Screening in Italy: the Importance of an Integrated Diagnostic Approach. J Inherit Metab Dis. 2010;33 Suppl 3:S91-4. PubMed PMID: 20157782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by expanded newborn metabolic screening in Italy: the importance of an integrated diagnostic approach. AU - Catanzano,Francesca, AU - Ombrone,Daniela, AU - Di Stefano,Cristina, AU - Rossi,Anna, AU - Nosari,Norberto, AU - Scolamiero,Emanuela, AU - Tandurella,Igor, AU - Frisso,Giulia, AU - Parenti,Giancarlo, AU - Ruoppolo,Margherita, AU - Andria,Generoso, AU - Salvatore,Francesco, Y1 - 2010/02/16/ PY - 2009/10/16/received PY - 2009/12/04/accepted PY - 2009/11/19/revised PY - 2010/2/17/entrez PY - 2010/2/17/pubmed PY - 2014/4/9/medline SP - S91 EP - 4 JF - Journal of inherited metabolic disease JO - J. Inherit. Metab. Dis. VL - 33 Suppl 3 N2 - 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. SN - 1573-2665 UR - https://www.unboundmedicine.com/medline/citation/20157782/The_first_case_of_mitochondrial_acetoacetyl_CoA_thiolase_deficiency_identified_by_expanded_newborn_metabolic_screening_in_Italy:_the_importance_of_an_integrated_diagnostic_approach_ L2 - https://doi.org/10.1007/s10545-009-9028-3 DB - PRIME DP - Unbound Medicine ER -