Outcomes are excellent after repair of double aortic arch, although persistent respiratory symptoms are frequent and probably associated with previous compression-related maldevelopment of the trachea and major airways.

COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts.

Very long-chain acyl-CoA dehydrogenase deficiency (MIM 201475) is a severe defect of mitochondrial energy production from oxidation of very long-chain fatty acids. This inherited metabolic disorder often presents in early neonatal period with episodes of symptomatic hypoglycemia usually responding well to intravenous glucose infusion. These babies are often discharged without establishment of diagnosis but return by 2-5 months of age with severe and progressive cardiac failure due to hypertrophic cardiomyopathy with or without hepatic failure and steatosis. An early diagnosis and treatment with high concentration medium chain triglycerides based feeding formula can be life saving in such patients. Here, we report the first diagnosed and treated case of Very long-chain acyl-CoA dehydrogenase deficiency in Oman. This infant developed heart failure with left ventricular dilation, hypertrophy and pericardial effusion at the age of 7 weeks. Prompt diagnosis and subsequent intervention with medium chain triglycerides-based formula resulted in a reversal of severe clinical symptoms with significant improvement of cardiac status. This treatment also ensured normal growth and neurodevelopment. It is stressed that the disease must be recognized by the pediatricians and cardiologists since the disease can be identified by Tandem Mass Spectrometry; therefore, it should be considered to be included in expanded newborn screening program, allowing early diagnosis and intervention in order to ensure better outcome and prevent complications.

Objective: Patients with inherited long QT syndrome (LQTS) are prone to torsade de pointes and sudden death (SD). Identifying affected individuals is important for SD prevention. This study aimed to determine the cause and genotype-phenotype characteristics of LQTS in a large Omani family. Methods: Upon LQTS diagnosis of a 5-year-old girl (proband), targeted mutation screening was performed based on the gene-specific ECG pattern identified in her mother. ECG-guided family genotyping was conducted for identifying additional affected individuals. Results: ECGs of the proband demonstrated 2:1 AV block, incomplete right bundle branch block (IRBBB) and markedly prolonged QTc (571-638 ms) with bizarre T waves. Cardiac imaging revealed dilatation of the ascending aorta and pulmonary artery, and left ventricular non-compaction. Her parents were first cousins. Both showed mild QT prolongation, with the mother presenting a LQT2 T wave pattern and the father IRBBB. Targeted KCNH2 screening identified a novel homozygous frameshift mutation p.T1019Pfs × 38 in the proband within 3 days. Family genotyping uncovered 3 concealed LQT2 and confirmed 11 members showing LQT2 ECG patterns as heterozygous mutation carriers. All heterozygous carriers were asymptomatic, with 71% showing normal to borderline prolonged QTc (458 ± 33 ms, range 409-522 ms). Conclusion: p.T1019Pfs × 38, a novel KCNH2 mutation, has been identified in a large LQTS family in Oman. Consanguineous marriages resulted in a homozygous with severe LQTS. ECG-guided phenotyping and genotyping achieved a high efficiency. Genetic testing is essential in identifying concealed LQTS. Further investigation is warranted to determine if there is a causative relationship between homozygous p.T1019Pfs × 38 and cardiovascular anomaly.

Echocardiography had a significant impact on the management of PICU patients. Such salutary effect was consequently reflected on the outcome. Pediatric intensivists are encouraged to acquire such bedside skill.