Transient N-glycosylation abnormalities likely due to a de novo loss-of-function mutation in the delta subunit of coat protein I.

Accurate glycosylation of proteins is essential for their function and their intracellular transport. Numerous diseases have been described, where either glycosylation or intracellular transport of proteins is impaired. Coat protein I (COPI) is involved in anterograde and retrograde transport of proteins between endoplasmic reticulum and Golgi, where glycosylation takes place, but no association of defective COPI proteins and glycosylation defects has been described so far. We identified a patient whose phenotype at a first glance was reminiscent of PGM1 deficiency, a disease that also affects N-glycosylation of proteins. More detailed analyses revealed a different disease with a glycosylation deficiency that was only detectable during episodes of acute illness of the patient. Trio-exome analysis revealed a de novo loss-of-function mutation in ARCN1, coding for the delta-COP subunit of COPI. We hypothesize that the capacity of flow through Golgi is reduced by this defect and at high protein synthesis rates, this bottleneck also manifests as transient glycosylation deficiency.

Minimally invasive pulmonary valve replacement through a left anterior minithoracotomy in young patients with pectus excavatum. The procedure of choice.

This case series presents two young patients with severe pulmonary valve regurgitation and pectus excavatum. Both patients underwent surgical repair of tetralogy of Fallot and pulmonary valvulotomy, respectively, during infancy and remained under close cardiological monitoring thereafter. After the diagnosis of severe pulmonary regurgitation was confirmed, both were referred to our center for pulmonary valve replacement. Minimally invasive pulmonary valve replacement was performed through a left anterior minithoracotomy. The swift recovery and return to daily activities observed in the presented cases suggest that minimally invasive pulmonary valve replacement through a left anterior minithoracotomy could indeed be considered the procedure of choice for patients with pectus excavatum.

Heterotaxy and cardiac defect in a girl with chromosome translocation t(X;1)(q26;p13.1) and involvement of ZIC3.

We report on a 2-year-old girl with situs ambiguus comprising right-sided stomach and spleen, left-sided liver and complex cardiac defect. Psychomotor development of this patient was normal, and no other major abnormalities were present. Chromosome analysis revealed a de novo balanced chromosome translocation t(X;1)(q26;p13.1). Molecular cytogenetic investigations identified a breakpoint spanning BAC clone on the X-chromosome containing the ZIC3 gene. Mutations in ZIC3 are associated with situs ambiguus and cardiac defects predominantly in males. This is the first report of a live born girl with an X-autosome translocation involving the ZIC3 region.

Successful management of an extreme example of neonatal hyperprostaglandin-E syndrome (Bartter's syndrome) with the new cyclooxygenase-2 inhibitor rofecoxib.

OBJECTIVE: To describe the successful treatment of an unusual case of severe neonatal Bartter's syndrome refractory to treatment with indomethacin. DESIGN: Case report, clinical. SETTING: Tertiary care intensive care unit. PATIENTS: A patient with neonatal hyperprostaglandin-E syndrome and excessive requirements of intravenous (via central venous catheter) water and salt supplementation, failure to thrive, vomiting, and massive growth retardation, despite adequate treatment with indomethacin. MAIN RESULT: Four weeks after induction of the new cyclooxygenase-2 inhibitor rofecoxib, the patient was well, on full enteral feeds, thriving, and had gained 600 g in weight. A lower supplementary potassium, magnesium, and sodium intake was required. Reinstitution of indomethacin therapy resulted in severe deterioration, despite high indomethacin doses; symptoms improved again after rofecoxib administration. No side effects have been seen thus far. CONCLUSION: This report shows that in selected patients with a severe form of neonatal Bartter's syndrome, the new cyclooxygenase-2 inhibitor rofecoxib may control the clinical symptoms of hyperprostaglandin-E syndrome after ineffective indomethacin therapy.

Successful management of a resistant renal artery stenosis in a child using a 4 mm cutting balloon catheter.

Percutaneous transluminal renal angioplasty (PTRA) is a well-established method to treat renal artery stenosis (RAS) in children and adults. However, a significant number of stenoses might not be treated by interventional techniques due to the inability to dilate the RAS. Conventional balloon angioplasty with a high-pressure coronary angioplasty balloon at 20 atm was unable to dilate a significant RAS in a 12-year-old child with severe renovascular hypertension (RR 195/125 mm Hg). After using a 4 mm cutting balloon, we achieved wide patency of the renal artery and an instant normalization of blood pressure without further need of antihypertensive therapy. PTRA using the cutting balloon technique may offer an additional therapeutic option for selected patients in whom conventional balloon angioplasty was not able to dilate RAS.