NMNAT3 deficiency: a novel red blood cell enzymopathy causing hemolysis by altering NAD levels and glycolysis

T Titine J. J. Ruiter (1Metabolic Diagnostics, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands) B Brigitte A. van Oirschot (2Red Blood Cell Research Group, Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht, The Netherlands) E Esmé Waanders (3Genome Diagnostics, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands) K Klaas Koop (4Department of Pediatrics, Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands) W Wouter W. van Solinge (2Red Blood Cell Research Group, Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht, The Netherlands) R Richard van Wijk J Judith J. M. Jans (1Metabolic Diagnostics, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands) M Marije Bartels (5Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveld Clinic, University Medical Center Utrecht, Utrecht, The Netherlands)

Abstract

Abstract We describe, to our knowledge, the first case of nicotinamide mononucleotide adenylyl transferase 3 (NMNAT3) deficiency, a novel red cell enzymopathy that causes reduced NAD levels and mild hemolytic anemia, which improved upon NAD precursor supplementation. We therefore propose testing for NMNAT3 variants in unexplained hereditary hemolytic anemia.

Article Details

Journal Blood
Volume / Issue Vol. 146, Issue 26
Published December 25, 2025
Pages 3246-3249
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (8)

T

Titine J. J. Ruiter

1Metabolic Diagnostics, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

B

Brigitte A. van Oirschot

2Red Blood Cell Research Group, Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht, The Netherlands

E

Esmé Waanders

3Genome Diagnostics, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

K

Klaas Koop

4Department of Pediatrics, Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands

W

Wouter W. van Solinge

2Red Blood Cell Research Group, Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht, The Netherlands

R

Richard van Wijk

J

Judith J. M. Jans

1Metabolic Diagnostics, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

M

Marije Bartels

5Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveld Clinic, University Medical Center Utrecht, Utrecht, The Netherlands