Lactic acidosis in a newborn with adrenal calcifications.
A patient is reported who presented in the newborn period with an unusual combination of congenital lactic acidosis and bilateral calcifications in the adrenal medulla, visible on standard abdominal x-ray and ultrasound examination. At birth, the proband was hypotonic and dystrophic. She developed respiratory insufficiency, cardiomegaly, and hepatomegaly and died at the age of 38 d. Examination of postmortem heart muscle revealed multiple areas of myocardial infarction with dystrophic calcifications. In the medulla of the adrenal glands, foci of necrosis and calcifications, and in the liver, multiple zones of necrosis and iron deposition were detected. Biochemical analysis in heart muscle revealed a decreased activity of complex IV of the oxidative phosphorylation (OXPHOS) and in liver a combined deficiency involving the complexes I, III, IV, and V. The findings were suggestive of a defect in biosynthesis of the mitochondrially encoded subunits of the OXPHOS complexes. Extensive analysis of the proband's mitochondrial DNA revealed neither pathogenic deletions and point mutations nor copy number alterations. Relative amounts of mitochondrial transcripts for the ribosomal mitochondrial 12S rRNA (12S) and mitochondrial 16S rRNA (16S) were significantly increased suggesting a compensatory mechanism involving the transcription machinery to low levels of translation. The underlying molecular defect has not been identified yet.
Zecic
Alexandra
A
Department of Neonatology, Ghent University Hospital, Ghent 9000, Belgium.
Smet
Joél E
JE
De Praeter
Claudine M
CM
Vanhaesebrouck
Piet
P
Viscomi
Carlo
C
Van Den Broecke
Caroline
C
De Paepe
Boel
B
Lohse
Peter
P
Martin
Jean-Jacques
JJ
Jackson
Joshua G
JG
Campbell
Colin R
CR
De Meirleir
Linda J
LJ
Zeviani
Massimo
M
Seneca
Sara H
SH
Lissens
Willy
W
Van Coster
Rudy N
RN
D000140:Acidosis, Lactic / Q000151:congenital / Q000378:metabolism / Q000473:pathology; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology*; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV; D017809:Fatal Outcome; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism
D045222:Electron Transport Chain Complex Proteins; D021122:Protein Subunits; D003576:Electron Transport Complex IV