FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome: A rare cause of hyperammonemia


Kahraman A. B., Çelik H., BAĞCI Z., Sezer A., KILIÇ M. K.

Molecular Genetics and Metabolism Reports, cilt.43, 2025 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 43
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.ymgmr.2025.101206
  • Dergi Adı: Molecular Genetics and Metabolism Reports
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals
  • Anahtar Kelimeler: Mitochondrial DNA depletion syndromes, Encephalopathy, Lactic acidosis, Hyperammonemia, FBXL4 gene
  • Sağlık Bilimleri Üniversitesi Adresli: Evet

Özet

Introduction: FBXL4- related encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome is caused by pathogenic variants in the FBXL4 gene, resulting in mitochondrial dysfunction and multisystem involvement. Hyperammonemia is reported in 45 % of cases but extremely elevated ammonia levels are rare. Case presentation: A male infant presented with dysmorphic features, hypotonia, failure to thrive, and lactic acidosis and severe hyperammonemia (ammonia: 1495 μmol/L). Genetic testing identified a homozygous FBXL4 pathogenic variant. Conclusion: To our knowledge, this report presents a neonatal case of FBXL4-related mtDNA depletion syndrome with the highest hyperammonemia level. This case emphasizes the importance of FBXL4 genetic testing in neonates with multisystem involvement, hyperammonemia, and dysmorphic features.