A novel mutation in COQ2 leading to fatal infantile multisystem disease.

Coenzyme Q10 (ubiquinone or CoQ10) serves as a redox carrier in the mitochondrial oxidative phosphorylation system. The reduced form of this lipid-soluble antioxidant (ubiquinol) is involved in other metabolic processes as well, such as preventing reactive oxygen species (ROS) induced damage from the mitochondrial membrane. Primary coenzyme Q10 deficiency is a rare, autosomal recessive disorder, often presenting with neurological and/or muscle involvement. Until now, five patients from four families have been described with primary coenzyme Q10 deficiency due to mutations in COQ2 encoding para-hydroxybenzoate polyprenyl transferase. Interestingly, four of these patients showed a distinctive renal involvement (focal segmental glomerular sclerosis, crescentic glomerulonephritis, nephrotic syndrome), which is only very rarely seen in correlation with mitochondrial disorders. The fifth patient deceases due to infantile multi organ failure, also with renal involvement. Here we report a novel homozygous mutation in COQ2 (c.905C>T, p.Ala302Val) in a dizygotic twin from consanguineous Turkish parents. The children were born prematurely and died at the age of five and six months, respectively, after an undulating disease course involving apneas, seizures, feeding problems and generalized edema, alternating with relative stable periods without the need of artificial ventilation. There was no evidence for renal involvement. We would like to raise awareness for this potentially treatable disorder which could be under diagnosed in patients with fatal neonatal or infantile multi-organ disease.

Congenital diaphragmatic hernia: a modern day approach.

Centralization of all complicated congenital diaphragmatic hernias (CDH) was organized in Germany from 1998, collecting 325 consecutive patients with striking increasing survival rates. This series report 244 patients from 2002 to 2007. Today, large defects are detected early in pregnancy by ultrasound and magnetic resonance imaging (MRI). In extracorporeal membrane oxygenation (ECMO) patients, prenatal lung head ratio (LHR) was 1.2 (median) at the 34th week of gestation or less than 25 ml lung tissue in MRI. This means that all patients below LHR of 1.4 should be transferred prenatally in a tertiary center. High risk group for survival was defined as LHR below 0.9, ie, 10 ml in MRI planimetry. Inborn patients show better results than outborns. In algorithm therapy, gentle ventilation plays an important role in preventing damage to the lung tissue and avoiding long term ventilation. When PaCO(2) was more than 75 mmHg, ventilation was changed to high frequency oscillatory ventilation (HFOV). Indication for ECMO was seen in preductal PaO(2) less than 50 mmHg over 2-4 h or less than 40 mmHg over 2 h. ECMO related risks included intracerebral bleeding (9%), intrapulmonary bleeding (14%), and convulsions (16%). Surgically, a longitudinal midline incision for exposure of the defect, the duodenal kinking, and probably for abdominal patching was perfect. A cone formed goretex patch provided more abdominal space and reduced abundant intrathoracical cavity. No drain was used. Postoperative complications were described. Overall survival in 244 consecutive patients was 86.5% for all patients born alive. All those who needed ECMO survived in 71%, underlining ECMO as a treatment of last choice. Follow-up for quality of life after CDH is described.