Mitochondrial DNA depletion presenting prenatally with skin edema and multisystem disease immediately after birth

Abstract

We describe two newborn sisters who presented in the third trimester with diminished fetal movements and skin edema, but with no other signs of hydrops fetalis. Within hours of birth, both developed profound lactic acidemia, followed by multi-organ failure. In muscle mitochondria, the activity of all enzymatic complexes that contain mitochondrial DNA (mtDNA)-encoded subunits was markedly decreased. Southern blot analysis revealed a profound reduction in the mtDNA/nuclear DNA ratio, implying mtDNA depletion. The prenatal identification of skin edema in two patients with mtDNA depletion, and its absence in a healthy sibling, suggest that skin edema should be regarded as a novel manifestation of mtDNA depletion. This finding shows that mtDNA depletion can present prenatally and, consequently, may aid the clinician in making a diagnosis, prenatally, of this genetic defect.

A case of prenatal chronic intestinal pseudo‐obstruction associated with Leigh syndrome

“…Although some affect only a single organ, they can commonly affect multiple organs, including the gastrointestinal tract . The reported abnormal fetal ultrasound findings associated with mitochondrial disorders include periventricular pseudocysts and skin edema with diminished fetal movements . Based on these data and our case, if a nonspecific abnormal fetal ultrasound finding is detected, it might be the only feature to suggest a mitochondrial disorder.…”

Pathology of Mitochondrial Encephalomyopathies

“…The latter leads to multisystemic failure in liver, kidneys and heart, as well as edema or bullous cutaneous lesions or even epidermolysis, generalized muscle weakness and encephalopathy. [46][47][48][49][50][51][52][53] As with Leigh encephalopathy, most infants have This child has significantly low activities of all five respiratory enzymes, with normal citrate synthase, the latter indicating a normal number of mitochondria; the activity defects were confirmed as ratios to citrate synthase. No mtDNA point mutations or deletions were demonstrated.…”

Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation

“…Based on the enzymatic findings, a defect in the synthesis of the mitochondrial-encoded proteins was assumed. Initially, Southern blot analysis of muscle DNA revealed normal sized mtDNA but decreased mtDNA content, suggesting mtDNA depletion 3. A similarly affected daughter was recently born, enabling homozygosity mapping analysis in the family, concomitant with revision of the molecular studies.…”