The human mitochondrial DNA (mtDNA) genome (16.6kb) is exclusively involved in the mitochondrial energy generation pathway of the cell. Therefore, knowledge of the mitochondrial genome and its DNA alterations is essential in identifying functional defects of the respiratory chain. During the last decade a growing list of mitochondrial point mutations, deletions and duplications have been associated with various degenerative diseases.We have identified a microdeletion in the mtDNA of lymphocytes and cultured skin fibroblasts of a baby girl. The newly discovered deletion is located at nucleotides 9204-9205 of the mt-ATPase subunit 6 gene and removes the cleavage site between the ATPase 6 and COIII mRNAs. This is of interest because these mRNAs are normally cleaved apart from a polycistronic transcript in the absence of an intervening tRNA, in what might be a novel mechanism for control of gene expression.
CASE REPORTThe female patient was born at term after an uncomplicated pregnancy and delivery, as the first child of healthy nonconsanguineous parents. There was no family history of neuromuscular or neurological disease in the family. Birth weight was 2.97kg, length 48cm and head circumference 33.8cm. On the third day of life, the child developed hypothermia, seizures and dehydration. Hyperlactataemia ranging from 3.9 to 7.1 mmol~ and compensated metabolic acidosis (pH 7.29-7.31) were found with normal plasma pyruvate. Initial treatment with intravenous fluids, phenobarbital and L-carnitine was started. Lactic acidosis resolved progressively within 2 weeks. A brain magnetic resonance imaging (MRI) showed a subarachnoid haemorrhage at the level of the occipital and posterior fossa.
Ten indicators available during the first two hours of life, such as clinical criteria of neonatal distress and postnatal arterial blood gases, were compared with the neonatal neurological course in sixty full term newborns with significant birth asphyxia in order to test their value for the diagnosis and the short-term prognosis of severe birth asphyxia. Birth asphyxia was defined as severe when it was followed by symptoms of moderate or severe post-asphyxial encephalopathy. We calculated a sensitivity lower than fifty percent for clinical criteria such as delay in establishing regular respiration and Apgar scores. It was clear that normal delay in establishing regular respiration and normal Apgar scores do not exclude severe birth asphyxia. Arterial pH and base deficit at thirty minutes of life were found to be the best criteria for the diagnosis of severe birth asphyxia, but lacked positive predictive value. The best predictive tool for the short-term neurological prognosis of birth asphyxia was a single score established at 30 minutes of life and based on the evaluation of consciousness, respiration and neonatal reflexes. Some aspects of the pathophysiology of birth asphyxia and the rationale for treatment of post-asphyxial metabolic acidosis are discussed.
It is illustrated that phase-sensitive inversion-recovery MR images are particularly well suited for the monitoring of brain maturation and myelination in the neonate and young infant. Provided appropriate timings are applied with the inversion-recovery MR pulse sequence, the myelinated areas show up as bright spots in the phase-sensitive images. The chronology of the appearance, and the location of these hyperintense zones correlate well with the chronology of brain maturation, as assessed by other means. In particular, the progressive functional capabilities of the infant correlate well with the progress of myelination, as exhibited by the MR images.
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