Case Report: Two Families With HPDL Related Neurodegeneration

Ieva Micule (Coresponding Author), Baiba Lace, Nathan T Wright, Nicolas Chrestian, Jurgis Strautmanis, Mikus Diriks, Janis Stavusis, Dita Kidere, Elfa Kleina, Anna Zdanovica, Nataly Laflamme, Nadie Rioux, Samarth Thonta Setty, Sander Pajusalu, Arnaud Droit, Monkol Lek, Serge Rivest, Inna Inashkina

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


There are recent reports of associations of variants in the HPDL gene with a hereditary neurological disease that presents with a wide spectrum of clinical severity, ranging from severe neonatal encephalopathy with no psychomotor development to adolescent-onset uncomplicated spastic paraplegia. Here, we report two probands from unrelated families presenting with severe and intermediate variations of the clinical course. A homozygous variant in the HPDL gene was detected in each proband; however, there was no known parental consanguinity. We also highlight reductions in citrate synthase and mitochondrial complex I activity detected in both probands in different tissues, reflecting the previously proposed mitochondrial nature of disease pathogenesis associated with HPDL mutations. Further, we speculate on the functional consequences of the detected variants, although the function and substrate of the HPDL enzyme are currently unknown.

Original languageEnglish
Article number780764
JournalFrontiers in Genetics
Issue number780764
Publication statusPublished - 2022
Externally publishedYes


  • ataxia
  • brain diseases
  • citrate-synthase
  • mitochondrial diseases
  • spastic paraplegia

Field of Science*

  • 3.2 Clinical medicine
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


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