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.

Forearm deoxyhemoglobin and deoxymyoglobin (deoxy[Hb + Mb]) measured by near-infrared spectroscopy (NIRS) using a handgrip test in mitochondrial myopathy.

The purpose of this paper is to test whether peripheral oxygenation responses measured with near-infrared spectroscopy (NIRS) would differ between patients suffering from mitochondrial myopathy (MM) and healthy controls during an incremental handgrip exercise test. Two groups of subjects were studied: 11 patients with MM and 11 age- and gender-matched untrained healthy controls. A handgrip exercise until exhaustion protocol was used consisting of 2 min periods of work (½ Hz) at different intensities, separated by a 60 s rest period. The changes in deoxyhemoglobin and deoxymyoglobin (deoxy[Hb + Mb]) during each work step were expressed in percent to the maximum deoxy[Hb + Mb]-value measured during arterial occlusion in forearm muscles. A repeated measures analysis of variance was used to compare the increase in deoxy[Hb + Mb] between MM patients and controls with increasing intensity. Statistical analysis revealed a significant difference between both populations (P < 0.001) indicating that the increase in deoxy[Hb + Mb] showed a significantly different pattern in the two populations. In the post hoc analysis significant lower deoxy[Hb + Mb] -values were found for MM patients at every intensity. The results of this paper show significantly different skeletal muscle oxygenation responses, measured with an optical method as NIRS, between MM patients and age- and gender-matched healthy subjects at submaximal and maximal level during an incremental handgrip exercise. This optical method is thus a valuable tool to assess differences in peripheral oxygenation. Moreover, this method could be used as an evaluation tool for follow up in interventional pharmacological studies and rehabilitation programs.