title: Fatal neonatal-onset mitochondrial respiratory chain disease with T cell immunodeficiency.
abstract: 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.
authors.affiliation: Department of General Paediatrics, JW Goethe University Frankfurt, 60590 Frankfurt, Germany. janine.reichenbach@kispe.unizh.ch
authors.forename: Janine
authors.initials: J
authors.lastname: Reichenbach
authors.forename: Ralf
authors.initials: R
authors.lastname: Schubert
authors.forename: Rita
authors.initials: R
authors.lastname: Horvàth
authors.forename: Jens
authors.initials: J
authors.lastname: Petersen
authors.forename: Nancy
authors.initials: N
authors.lastname: Fütterer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Malle
authors.forename: Andreas
authors.initials: A
authors.lastname: Stumpf
authors.forename: Boris R
authors.initials: BR
authors.lastname: Gebhardt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.forename: Stefan
authors.initials: S
authors.lastname: Zielen
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics; D004406:Dysgammaglobulinemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D045222:Electron Transport Chain Complex Proteins / Q000172:deficiency*; D017809:Fatal Outcome; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D008297:Male; D028361:Mitochondrial Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*
chemical_list: D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D007136:Immunoglobulins