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Case Reports
. 2024 Aug 29:41:101137.
doi: 10.1016/j.ymgmr.2024.101137. eCollection 2024 Dec.

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

Rai-Hseng Hsu  1   2   3 , Ni-Chung Lee  1   2   3 , Hui-An Chen  1   2   3 , Wuh-Liang Hwu  2   4 , Wang-Tso Lee  1   3 , Yin-Hsiu Chien  1   2   3
Affiliations
Case Reports

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

Rai-Hseng Hsu et al. Mol Genet Metab Rep. .

Abstract

D-bifunctional protein (DBP) deficiency, a fatal peroxisomal enzyme disorder, typically manifests with life-threatening symptoms in the first two years of childhood. We present the case of an infant with elevated lysophosphatidylcholine C26:0 (C26:0-LPC) levels identified during X-linked adrenoleukodystrophy (ALD) screening, leading to a diagnosis of DBP deficiency due to a homozygous HSD17B4 c.1041T>A, p.(Tyr347Ter) variant. Starting at two months of age, the infant experienced seizures, hypotonia, and developmental delays, prompting the initiation of experimental treatment with the readthrough agent PTC124 (ataluren) at six months. The treatment led to a decrease in C26:0-LPC levels from 0.65 μM to 0.53 μM; concomitant fish oil supplementation transiently increased C26:0-LPC to 0.74 μM before returning to 0.53 μM after cessation of supplementation. The patient demonstrated improved swallowing and progressive motor and speech development during a two-year treatment period, with no further seizures. This case report highlights the potential of nonsense readthrough therapy for peroxisomal disorders, a group of metabolic diseases that currently lack targeted treatments.

Keywords: D-bifunctional protein deficiency; PTC124 (ataluren); Readthrough therapy; Uniparental disomy.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Trends in C26:0-LPC level, motor development, and treatment duration.
See this image and copyright information in PMC

References

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