Antenatal manifestations of mitochondrial disorders

Abstract

Introduction: Mitochondria are crucial organelles of the cell and its main function is to produce and provide energy for cellular metabolism in most organs and tissues, through a process called oxidative phosphorylation. Mitochondrial respiratory chain diseases are a heterogeneous group of pathologies due to genetic mutations affecting mitochondrial energy production. The estimated incidence is approximately 1:10.000 births. A defect of oxidative phosphorylation can theoretically lead to any symptoms, in any organ or tissue, at any age or even before birth. Objective: To identify the frequency of antenatal manifestations of mitochondrial respiratory chain disorders, characterize the phenotypes and identify possible associations between mitochondrial respiratory chain disorders and a more specific and earlier manifestation or diagnostic disclosure of these diseases. Methods and subjects: The files of a group of pediatric subjects with mitochondrial respiratory chain disease identified in the first decade of life at the Laboratory of Biochemistry Genetics-Centre for Neuroscience and Cell Biology and Faculty of Medicine, University of Coimbra, in a period of 10 years (2000-2010) were retrospectively reviewed. The results of prenatal and birth history were compared with a control group, which included 2 healthy infants matching patients by the month and year of birth, for each case of a child with mitochondrial disease diagnosis Results [patients (group A)(n=45) versus controls (group B)(n=90)]: Maternal age was (mean ±standard deviation) 28.4±6.5 and 28.3±4.7 years, respectively. Gestacional age at delivery was 38.8±1.7 and 38.5±2.6 weeks. The ratio of children gender (male: female) was 0.73 vs 1 and birth weight at delivery was 2923.2±554.2 vs 3246.6±460.2 grams (p=0.001). Concerning family history, neurologic diseases were found in 9 vs 5 cases and genetic diseases in 2 vs 0. Fifteen pregnancies of group A were considered abnormal. The anomalies observed were: intrauterine growth restriction (n=9), oligohydramnios (n=2), preterm delivery (n=2), fetal anemia/anasarca (n=1), maternal infection with varicella (n=1), poor fetal movements (n=1). Neonatal morbidity is significantly higher (5 fold) in group A (p<0.001). Conclusions: Intrauterine growth restriction was the most frequent antenatal feature observed. Some patients presented isolated antenatal manifestations, such as oligohydramnios and decrease fetal movements. The present work is a relevant contribution, but more studies are needed, in order to study mitochondrial physiology and activity in embryological development for the assessment of the mitochondrial disease development in fetal life. This knowledge will probably contribute to improve our ability to suspect and/or diagnose a mitochondrial respiratory chain disorder from an antenatal manifestation