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Beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase, T2) deficiency (OMIM #203750, *607809) is an inborn error of metabolism that affects isoleucine catabolism and ketone body metabolism. This disorder is clinically characterized by intermittent ketoacidotic crises under ketogenic stresses. In addition to a previous 26-case series, four series of T2-deficient patients were recently reported from different regions. In these series, most T2-deficient patients developed their first ketoacidotic crises between the ages of 6 months and 3 years. Most patients experienced less than three metabolic crises. Newborn screening (NBS) for T2 deficiency is performed in some countries but some T2-deficient patients have been missed by NBS. Therefore, T2 deficiency should be considered in patients with severe metabolic acidosis, even in regions where NBS for T2 deficiency is performed. Neurological manifestations, especially extrapyramidal manifestations, can occur as sequelae to severe metabolic acidosis; however, this can also occur in patients without any apparent metabolic crisis or before the onset of metabolic crisis.

Mitochondrial acetoacetyl-CoA thiolase (12) deficiency is an inborn error of metabolism affecting isoleucine catabolism and ketone body utilization. This disorder is clinically characterized by intermittent keto-acidotic episodes with no clinical symptoms between episodes. In general, 12 gene mutations are heterogenous. No common mutations have been identified and more than 70 mutations have been identified in 70 patients with 12 deficiency (including unpublished data). We herein identified a common mutation, R208X, in Vietnamese patients. We identified R208X homozygously in six patients and heterozygously in two patients among eight Vietnamese patients. This R208X mutation was also identified heterozygously in two Dutch patients, however, R208X mutant alleles in the Vietnamese have a different haplotype from that in the Dutch, when analyzed using Msp I and Tag I polymorphisms in the T2 gene. The R208X mutant allele was not so frequent in the Vietnamese since we could not find that mutant allele in 400 healthy Vietnamese controls using the Nla III restriction enzyme assay. DNA diagnosis of 12 deficiency may be applicable to the Vietnamese population. (C) 2010 Elsevier Inc. All rights reserved.

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 [beta-ketothiolase (beta-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 beta-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. beta-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 beta-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.