Lack of NAD(P)+ transhydrogenase activity in patients with primary adrenal insufficiency due to NNT variants
An erratum to this article was published (Eur J Endocrinol, 30 Sep 2024 ↗)
Authors' conclusion
The manifestation of PAI in NNT-mutated patients is associated with a complete lack of NNT activity. Evaluation of NNT activity can be useful to characterize disease-causing NNT variants.
Study context
- Population
- Patients with primary adrenal insufficiency (PAI) due to genetically confirmed NNT variants, their heterozygous carrier parents, and healthy controls; blood samples (peripheral blood mononuclear cells (PBMCs))
- Participants
- 5 / 8 / 26
- Comparison
- PAI patients with NNT variants vs heterozygous carrier parents vs healthy controls
- Patientsn = 5
- Parentsn = 8
- Healthy controlsn = 26reference
- Outcome
- NNT activity by reverse reaction assay in digitonin-permeabilized PBMCs
Methodological detailsvalidated in mouse model of NNT absence
- Validated in mouse model of NNT absence
Main finding
As reported in the abstract
NNT activity in PBMCs
NNT activity undetectable in patients (<4% of healthy controls), independent of the pathogenic genetic variant
<4% of that of healthy controls
Further findings
NNT expression
- Mature NNT protein expression lower in patients than in control groups
- mRNA levels varied widely among genotypes
Mitochondrial bioenergetic function in PBMCs
- Pathogenic NNT variants did not impair mitochondrial bioenergetic function
Original publication
Lack of NAD(P)+ transhydrogenase activity in patients with primary adrenal insufficiency due to NNT variants. Eur J Endocrinol. Published 23 January 2024. doi:10.
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