Antenatal manifestations of mitochondrial respiratory chain deficiency.
OBJECTIVE
To review the antenatal manifestations of disorders of oxidative phosphorylation.


METHODS
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.
von Kleist-Retzow
Jürgen-Christoph
JC
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants-Malades, 149 Rue de Sèvres, 75743 Paris Cedex 15, France.
Cormier-Daire
Valérie
V
Viot
Géraldine
G
Goldenberg
Alice
A
Mardach
Becky
B
Amiel
Jeanne
J
Saada
Philippe
P
Dumez
Yves
Y
Brunelle
Francis
F
Saudubray
Jean-Marie
JM
Chrétien
Dominique
D
Rötig
Agnès
A
Rustin
Pierre
P
Munnich
Arnold
A
De Lonlay
Pascale
P
D001724:Birth Weight; D000013:Congenital Abnormalities; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000150:complications; D005318:Fetal Heart / Q000503:physiopathology; D005324:Fetal Movement / Q000502:physiology; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D028361:Mitochondrial Diseases / Q000196:embryology*; D011247:Pregnancy; D012189:Retrospective Studies; D016216:Ultrasonography, Prenatal