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Outcome in six patients with mitochondrial trifunctional protein disorders identified by newborn screening

Astrid Sperk1, Martina Mueller, Ute Spiekerkoetter

  • 1University Children's Hospital, Department of General Pediatrics, Moorenstr. 5, 40225 Duesseldorf, Germany.

Molecular Genetics and Metabolism
|July 28, 2010
PubMed

Insights

Newborn screening identifies trifunctional protein (TFP) deficiency, but these disorders remain life-threatening. Early identification is crucial, yet acute presentations still occur, highlighting the need for continued vigilance in managing TFP and LCHAD deficiencies.

Area of Science:

  • Biochemistry
  • Genetics
  • Pediatrics

Background:

  • Disorders of the mitochondrial trifunctional protein (TFP) complex, including long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), historically presented with severe outcomes before newborn screening.
  • Limited data exists on the prognosis and clinical outcomes of TFP deficiency disorders following the implementation of newborn screening programs.

Purpose of the Study:

  • To characterize the clinical presentation and molecular features of patients identified with TFP complex disorders through newborn screening.
  • To evaluate the effectiveness of newborn screening in identifying TFP deficiency and its impact on patient outcomes.

Main Methods:

  • Retrospective analysis of 6 screened patients with TFP complex disorders, including 3 with LCHADD.
  • Clinical and molecular characterization of identified cases.
  • Review of patient outcomes and comparison with historical data.

Main Results:

  • Three out of six screened patients presented with symptoms before screening results were available.
  • Among the three patients identified as asymptomatic by screening, one died acutely at 3 months due to infection.
  • Two patients remained asymptomatic under preventive care until age 3 years; one had a sibling with the same genotype who became symptomatic at 15 months.

Conclusions:

  • Newborn screening enables the identification of asymptomatic cases of TFP complex disorders.
  • Despite screening, TFP and LCHAD deficiencies remain critical, life-threatening conditions, with some patients experiencing acute presentations.
  • Outcomes for TFP deficiency contrast with other long-chain fatty acid oxidation defects identified through newborn screening.

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