Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from the newborn screening card by tandem mass spectrometry and DNA analysis

Dietrich Matern, Arnold W. Strauss, Steven L. Hillman, Ertan Mayatepek, David S. Millington, Friedrich Karl Trefz

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Trifunctional protein (TFP) plays a significant role in the mitochondrial β-oxidation of long-chain fatty acids. Its deficiency impairs the energy generating function of this pathway and causes hypoketotic hypoglycemia once hepatic glycogen stores are depleted. A Reye-like syndrome, cardiomyopathy, and sudden death may follow. The diagnosis is based on demonstration of significantly decreased enzyme activity of at least two of the three involved enzymes in fibroblasts. The possibility of prospective diagnosis of TFP deficiency by newborn screening using tandem mass spectrometry (MS/MS) has not been evaluated. We report the postmortem diagnosis of a male newborn, who suffered sudden death at 2 wk of age, and his younger sister, who died of cardiomyopathy complicated by acute heart failure at the age of 6 mo, after she had acquired a common viral infection. Blood spots from the original newborn screening cards were the only remaining material from the patients. Analysis by MS/MS revealed acylcarnitine profiles consistent with either TFP or long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency. To prove the diagnosis, the α- and β- subunit genes coding for TFP were examined. The patients were compound heterozygous for a 4-bp-deletion and an a→g missense mutation, both in the same exon 3 donor consensus splice site. This is the first report of the diagnosis of TFP deficiency using blood spots obtained for newborn screening and suggests that TFP deficiency may be detectable by prospective newborn screening using MS/MS.

Original languageEnglish (US)
Pages (from-to)45-49
Number of pages5
JournalPediatric Research
Volume46
Issue number1
StatePublished - Jul 1999
Externally publishedYes

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Tandem Mass Spectrometry
Newborn Infant
DNA
Sudden Death
Cardiomyopathies
Reye Syndrome
RNA Splice Sites
Liver Glycogen
Proteins
Virus Diseases
Missense Mutation
Enzymes
Hypoglycemia
Siblings
Exons
Consensus
Fatty Acids
Heart Failure
Fibroblasts
Trifunctional Protein Deficiency With Myopathy And Neuropathy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Matern, D., Strauss, A. W., Hillman, S. L., Mayatepek, E., Millington, D. S., & Trefz, F. K. (1999). Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from the newborn screening card by tandem mass spectrometry and DNA analysis. Pediatric Research, 46(1), 45-49.

Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from the newborn screening card by tandem mass spectrometry and DNA analysis. / Matern, Dietrich; Strauss, Arnold W.; Hillman, Steven L.; Mayatepek, Ertan; Millington, David S.; Trefz, Friedrich Karl.

In: Pediatric Research, Vol. 46, No. 1, 07.1999, p. 45-49.

Research output: Contribution to journalArticle

Matern, D, Strauss, AW, Hillman, SL, Mayatepek, E, Millington, DS & Trefz, FK 1999, 'Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from the newborn screening card by tandem mass spectrometry and DNA analysis', Pediatric Research, vol. 46, no. 1, pp. 45-49.
Matern, Dietrich ; Strauss, Arnold W. ; Hillman, Steven L. ; Mayatepek, Ertan ; Millington, David S. ; Trefz, Friedrich Karl. / Diagnosis of mitochondrial trifunctional protein deficiency in a blood spot from the newborn screening card by tandem mass spectrometry and DNA analysis. In: Pediatric Research. 1999 ; Vol. 46, No. 1. pp. 45-49.
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