Antenatal manifestations of mitochondrial respiratory chain deficiency

doi:10.1067/S0022-3476(03)00130-6

The Journal of Pediatrics

Volume 143, Issue 2, August 2003, Pages 208-212

https://doi.org/10.1067/S0022-3476(03)00130-6 Get rights and content

Abstract

Objective To review the antenatal manifestations of disorders of oxidative phosphorylation.

Study design A total of 300 cases of proven respiratory chain enzyme deficiency were retrospectively reviewed for fetal development, based on course and duration of pregnancy, antenatal ultrasonography and birth weight, length, and head circumference. Particular attention was given to fetal movements, oligo/hydramnios, fetal cardiac rhythm, fetal heart ultrasound, and ultrasonography/echo Doppler signs of brain, facial, trunk, limb, and organ anomalies.

Results Retrospective analyses detected low birth weight (<3rd percentile for gestational age) in 22.7% of cases (68/300, P<.000001). Intrauterine growth retardation was either isolated (48/300, 16%) or associated with otherwise unexplained anomalies (20/300, 6.7%, P<.0001). Antenatal anomalies were usually multiple and involved several organs sharing no common function or embryologic origin. They included polyhydramnios (6/20), oligoamnios (2/20), arthrogryposis (1/20), decreased fetal movements (1/20), ventricular septal defects (2/20), hypertrophic cardiomyopathy (4/20), cardiac rhythm anomalies (4/20), hydronephrosis (3/20), vertebral abnormalities, anal atresia, cardiac abnormalities, tracheoesophageal fistula/atresia, renal agenesis and dysplasia, and limb defects (VACTERL) association (2/20), and a complex gastrointestinal malformation (1/20).

Conclusions Although a number of metabolic diseases undergo a symptom-free period, respiratory chain deficiency may have an early antenatal expression, presumably related to the time course of the disease gene expression in the embryofetal period. The mechanism triggering malformations is unknown and may include decreased ATP formation and/or an alteration of apoptotic events controlled by the mitochondria.

Section snippets

Methods

A total of 300 cases of proven respiratory enzyme deficiency were retrospectively reviewed for fetal development, based on (1) course and duration of pregnancy, (2) antenatal ultrasonography, and (3) birth weight, length, and head circumference (OFC). Particular attention was given to fetal movements, oligo/hydramnios, fetal cardiac rhythm, fetal heart ultrasound, and ultrasonography/echo Doppler signs of brain, facial, trunk, limb, and organ anomalies.

Evidence of respiratory chain deficiency

Results

Intrauterine growth retardation (IUGR) suggestive of an antenatal expression of the disease was the most frequent antenatal feature in our series of respiratory enzyme deficiency. Retrospective analyses detected low birth weight (<3rd percentile for gestational age) in 22.7% of cases (68/300, P<.000001). Failure to thrive was either isolated (48/300, 16%) or associated with otherwise unexplained anomalies (20/300, 6.7%, P<.0001). By contrast, length, OFC, duration of pregnancy, and frequency of

Discussion

We report IUGR in a significant fraction of our patients (23% with proven respiratory chain deficiency). IUGR was either isolated (16%) or associated with antenatal anomalies of development (7%; total = 23%). Why most children had normal birth weight and antenatal development, whereas a fraction of them had a combination of IUGR and various malformations, remains unanswered. This feature should be related to the tissue specificity and/or the time course of respiratory enzyme gene expression in

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Original articleAntenatal manifestations of mitochondrial respiratory chain deficiency

Abstract

Section snippets

Methods

Results

Discussion

Clin Chim Acta

J Pediatr

Uridine preserves the expression of respiratory enzyme deficiencies in cultured fibroblasts

Eur J Pediatr

Mitochondrial biogenesis in early mouse embryos: expression of the mRNAs for subunits IV, Vb, VIIc of cytochrome c oxidase and subunit 9 (P1) of H (+)-ATP synthase

Mol Reprod Dev

Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice

Nat Genet

Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits

Nat Genet

Determination of enzyme activities for prenatal diagnosis of respiratory chain deficiency

Prenat Diagn

RSH (so-called Smith-Lemli-Opitz) syndrome

Curr Opin Pediatr

The Smith-Lemli-Opitz syndrome

J Med Genet

Original article
Antenatal manifestations of mitochondrial respiratory chain deficiency