Fatal neonatal-onset mitochondrial respiratory chain disease with T cell immunodeficiency

Pediatr Res. 2006 Sep;60(3):321-6. doi: 10.1203/01.pdr.0000233252.60457.cf. Epub 2006 Jul 20.


We present the clinical and laboratory features of a boy with a new syndrome of mitochondrial depletion syndrome and T cell immunodeficiency. The child suffered from severe recurrent infectious diseases, anemia, and thrombocytopenia. Clinically, he presented with severe psychomotor retardation, axial hypotonia, and a disturbed pain perception leading to debilitating biting of the thumb, lower lip, and tongue. Brain imaging showed hypoplasia of corpus callosum and an impaired myelinization of the temporo-occipital region with consecutive supratentorial hydrocephalus. Histologic examination of a skeletal muscle biopsy was normal. Biochemical investigation showed combined deficiency of respiratory chain complexes II+III and IV. MtDNA depletion was found by real-time PCR. No pathogenic mutations were identified in the TK2, SUCLA2, DGUOK, and ECGF1 genes. A heterozygous missense mutation was found in POLG1. The pathogenic relevance of this mutation is unclear. Interestingly, a lack of CD8(+) T lymphocytes as well as NK cells was also observed. The percentage of CD45RO-expressing cells was decreased in activated CD8(+) T lymphocytes. Activation of T lymphocytes via IL-2 was diminished. The occurrence of the immunologic deficiency in our patient with mtDNA depletion is a rare finding, implying that cells of the immune system might also be affected by mitochondrial disease.

Publication types

  • Case Reports

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Common Variable Immunodeficiency / immunology*
  • Common Variable Immunodeficiency / metabolism
  • Common Variable Immunodeficiency / pathology
  • DNA, Mitochondrial / genetics
  • Dysgammaglobulinemia / immunology*
  • Dysgammaglobulinemia / metabolism
  • Dysgammaglobulinemia / pathology
  • Electron Transport Chain Complex Proteins / deficiency*
  • Fatal Outcome
  • Humans
  • Immunoglobulins / biosynthesis
  • Immunoglobulins / blood
  • Infant
  • Infant, Newborn
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / pathology
  • Male
  • Mitochondrial Diseases / immunology*
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / pathology
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology*


  • DNA, Mitochondrial
  • Electron Transport Chain Complex Proteins
  • Immunoglobulins