Lactic Acidosis in a Newborn With Adrenal Calcifications

Abstract

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.

Mutation of the iron‐sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy

“…Respiratory chain complex enzyme activities were measured by spectrophotometric analysis as previously described (Zecic et al 2009). In addition, respiratory chain complexes of mitochondria isolated from skeletal muscle were separated by blue native polyacrylamide gel electrophoresis, followed by staining of the enzymatic activity in the gel, as reported previously (Van Coster et al 2001).…”

Cholestasis and Hepatic Iron Deposition in an Infant With Complex Glycerol Kinase Deficiency

“…There have, however, been several case reports of patients with adrenal insufficiency who were found to have increased hepatic iron deposition. 15,16 In addition, there is at least 1 reported case of improvement in liver failure after corticosteroid replacement for adrenal insufficiency, possibly indicating a relationship between these 2 disease processes. 17 Given this literature, it is possible that our patient's siderosis was related to his adrenal hypofunction and not simply a manifestation of our patient's initial acute hepatic injury.…”

Neonatal lactic acidosis explained by LARS2 defect

“…Back in the year 2009, we presented in this journal a neonate with an unusual combination of congenital lactic acidosis and bilateral calcifications in the adrenal medulla 1 . After prenatal ultrasound examination at 21 weeks had revealed intrauterine growth retardation and pericardial effusions, labor was induced at 38 weeks of pregnancy.…”

“…Nuclear-encoded mitochondrion-specific aminoacyl-tRNA synthetases exist for 17 of the 20 proteogenic amino acids, and pathogenic mutations have now been reported for each one of these 2 . At the time we published our casus, LARS2 defects had not been reported, yet between the year 2013 and now, a total of 23 patients have been described that carry disease-causing LARS2 variants (Table 1) 1,[3][4][5][6][7][8][9][10][11][12][13] . Their diverse associated disease phenotypes, which include Perrault syndrome, multisystem disease, leukodystrophy and intellectual disability, do not appear to have an obvious link with genotype.…”