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Ataluren-mediated nonsense variant readthrough in D-bifunctional protein deficiency: A case report

Rai-Hseng Hsu1,2,3, Ni-Chung Lee1,2,3, Hui-An Chen1,2,3

  • 1Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

Molecular Genetics and Metabolism Reports
|September 16, 2024
PubMed

Insights

D-bifunctional protein deficiency, a severe peroxisomal disorder, was treated in an infant using the readthrough agent ataluren. This experimental therapy showed promise by improving clinical symptoms and reducing specific biomarker levels.

Area of Science:

  • Biochemistry
  • Genetics
  • Pediatrics

Background:

  • D-bifunctional protein (DBP) deficiency is a fatal peroxisomal disorder impacting infants.
  • Early diagnosis is crucial for managing life-threatening symptoms.

Observation:

  • An infant diagnosed with DBP deficiency via HSD17B4 variant screening showed elevated C26:0-LPC levels.
  • The infant presented with seizures, hypotonia, and developmental delays within the first year of life.

Findings:

  • Treatment with PTC124 (ataluren) reduced C26:0-LPC levels from 0.65 μM to 0.53 μM.
  • Fish oil supplementation caused a transient increase in C26:0-LPC.
  • Over two years, the infant showed improved motor and speech development and no further seizures.

Implications:

  • Nonsense readthrough therapy, like ataluren, offers a potential treatment for DBP deficiency.
  • This approach may provide a targeted therapy for peroxisomal disorders lacking effective treatments.

Keywords:
D-bifunctional protein deficiencyPTC124 (ataluren)Readthrough therapyUniparental disomy

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