Mitochondrial A3243G Point Mutation Research Articles

Pulmonary hypertension in a child with mitochondrial A3243G point mutation

Mitochondrial diseases are a group of disorders caused by pathologic dysfunction of the mitochondrial respiratory chain that present with a wide range of clinical expression. Cardiorespiratory complications have previously been described in association with mitochondrial disease; however, pulmonary hypertension has rarely been reported. Pulmonary hypertension is characterized by elevated pulmonary arterial pressure and secondary right ventricular failure. It is a life-threatening condition with a poor prognosis if untreated. We report a case of 3-year-4-month-old boy who had mitochondrial A3243G point mutation with pulmonary hypertension. The unusual features of our case strengthen the concepts of pulmonary hypertension should be considered as another potential manifestation of mitochondrial disease.

Hyperkalemia in familial mitochondrial cytopathy

To contribute to understanding the pathogenesis of hyperkalemia that often occurs in patients with diabetes. We describe 3 familial cases of mitochondrial diabetes mellitus. The mitochondrial A3243G point mutation was confirmed in a mother and her 2 children. We examined their clinical features and pathological findings, and assessed heteroplasmy of mutant mitochondria DNA (mtDNA) by molecular analysis. The second son had spontaneous hyperkalemia and hyporeninemic hypoaldosteronism. Histopathological examination revealed severe tubulointerstitial and vascular changes around the juxtaglomerular apparatus. The mother only showed intermittent hyperkalemia concurrently with the aggravation of heart failure, and the pathological changes in her kidneys were mild. Heteroplasmy was more severe in the second son than in the mother. Heteroplasmy of mitochondrial cytopathy combined with diabetes mellitus led to abnormalities resembling those seen in Type IV renal tubular acidosis.

Another observation with VATER association and a complex IV respiratory chain deficiency

The VATER association of vertebral anomalies (V), anal atresia (A), esophageal atresia and/or tracheo-esophageal fistula (TE), radial and renal anomalies (R) is a common congenital association of unknown origin with probably heterogeneous causes. Here, we report on a girl presenting with pre- and postnatal growth retardation, esophageal atresia, vertebral and costal anomalies and a unilateral radial defect, consistent with the diagnosis of VATER association. In the first month of life, she presented with failure to thrive, severe episodes of hypoglycemia, liver dysfunction and high levels of lactate, which prompted us to perform metabolic screening. A complex IV respiratory chain deficiency (RCD) was diagnosed on a liver biopsy. The respiratory chain defect was not observed in skin fibroblasts. No mtDNA point mutation or deletion was identified. The girl is now 9 years old and has a normal mental development but persistent feeding difficulties and moderate hyperlactatemia. To our knowledge, this is the second report of VATER association with mitochondrial disorder. In a previous report, a VACTERL association was observed in a girl with the mitochondrial A3243G point mutation. The association of VATER phenotype with a mitochondrial disorder may be coincidental but could also suggest that the presence of multiple malformations is the result of the antenatal expression of RCD.