Antenatal manifestations of mitochondrial disorders

Abstract

Mitochondrial respiratory chain diseases are a heterogeneous group of pathologies caused by genetic alterations affecting mitochondrial energy production. Theoretically, this deficiency may lead to any symptoms, in any organ or tissue, at any age even before birth. The aim of our study was to identify the frequency and characterize antenatal manifestations identifying possible associations between mitochondrial disease and more specific and earlier manifestation. We retrospectively review the files of 44 paediatric subjects with genetic and biochemical alterations of respiratory chain identified in the first decade of life and compare data with a control group (n = 88). Our results show that maternal age was similar in both groups. The female gender was predominant in patients group. Gestational age at delivery was similar in both groups. Concerning birth weight, it was significantly lower (p = 0.001) in patients (2899.9 ± 538.3 vs. 3246.6 ± 460.2 g). Fifteen pregnancies of the patients group were considered abnormal. Our findings show that intrauterine growth restriction was the most frequent antenatal feature observed. Neonatal morbidity was significantly higher (fivefold) in patients (p < 0.001). The clinical findings are independent of the molecular defect type. Our results are preliminary and more studies are needed, in order to learn more about mitochondrial physiology and activity in embryological development for the assessment of mitochondrial disease progress in fetal life. However, the present work is a significant contribution, given the scarcity of information in this field.

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation

“…Abbreviations: D, deficiency; EO, early onset of symptoms (during the newborn period); f, female; LO, late onset of symptoms (after the newborn period); m, male; n/a, not applicable Okun et al 2002;S c h w a be ta l2006). It is therefore tempting to speculate that low birth weight in MMA patients might reflect antenatally impaired energy metabolism (Tavares et al 2013). Since PA and MMA share biochemical and pathomechanistic similarities, it remains to be elucidated why birth weights of these patients differed in our study.…”

Height as a Clinical Biomarker of Disease Burden in Adult Mitochondrial Disease

“…In our cohort birthweight and gestation data were not available. Studies looking at birth weight in mitochondrial disease have focused on patients with pediatric mitochondrial disease and have shown that they are significantly lighter than their counterparts; in one study ≤22% were below the third percentile for weight at birth (40, 41). We know that infants who are small for gestational age often attain a shorter final height than their larger counterparts, particularly if no catch-up growth is demonstrated within the first years of life.…”

Involvement of estrogen-related receptor-γ and mitochondrial content in intrauterine growth restriction and preeclampsia

“…A variety of studies in murine models and humans have revealed that mitochondrial protein mutations are associated with abnormally high frequencies of IUGR (38)(39)(40). Moreover, it has been demonstrated that mitochondrial DNA content, morphology, respiratory activity, and apoptosis are abnormal in IUGR and/or PE placentas (13,15,41,42).…”