Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation.

Hereditary orotic aciduria (HOA) is a very rare inborn error of pyrimidine metabolism. It results from a defect of the uridine-5-monophosphate synthase (UMPS) gene. To date, only about twenty patients have been described. We report a case of HOA with a novel variant in the UMPS gene. A 17-year-old Emirati girl was born to first-cousin parents. During the first year, she had recurrent, severe infections including disseminated varicella. After evaluation for immunodeficiency, an impression of immunodeficiency of unknown etiology was presumed. Frequent episodes of pancytopenia were also noted. Bone marrow biopsy showed trilineage megaloblastoid maturation with dysplastic changes that were refractory to hematinic therapy. Also, she was noted to have failure to thrive, developmental delay and epilepsy. She was referred to the Genetics clinic where whole-exome sequencing (WES) was done and showed a novel homozygous variant in the UMPS gene confirming a diagnosis of HOA. She was started on uridine triacetate after which she showed clinical, hematologic and biochemical improvement. Although extremely rare, hereditary orotic aciduria should be suspected in any child with megaloblastic bone marrow, immunodeficiency or when developmental delay and anemia coexist.

11 Years of the Fontan operation at a single institution: Results from 87 consecutive patients.

Fontan procedure is the preferred palliation for patients with single ventricles. OBJECTIVES: To evaluate early morbidity and mortality after Fontan operation in 87 consecutive patients, between 2007 and 2017. METHODS: Early survival, duration of intensive care unit (ICU), and hospital stays were the main outcomes evaluated. Potential influencing factors evaluated included preoperative and intraoperative variables. RESULTS: Fontan procedure was performed at a median age of 4.2 years (range, 17 months-26 years), and a median weight of 15.5 kg (range, 8-72 kg). Extracardiac Fontan was the procedure of choice. The median cardiopulmonary bypass time was 122 minutes (range, 58-550 minutes). The majority had a fenestration (75 out of 87). Postoperatively, the median duration of ICU stay and total hospital stay were (4, 1-76 days) and (16, 1-85 days), respectively. Fontan failure occurred in one patient (1%). Overall early survival was 94%, resulting in a mortality rate of 6%. Univariate analysis showed that heterotaxy (odds ratio [OR], 2.222; confidence interval [CI], 1.345-6.250; P = .003) and decreased ventricular function (OR, 2.207; CI, 1.348-6.061; P = .002) significantly decreased survival. The same analysis failed to identify any statistically significant risk factors for prolonged hospital and ICU stays. CONCLUSION: Our reported mortality and morbidity rates compared favorably with the reported rates. Therefore, Fontan operation can be performed in a tertiary care center in the United Arab Emirates with favorable early postoperative outcomes.

Congenital Combined Deficiency of the Vitamin K-dependent Clotting Factors (VKCFD): A Novel Gamma-glutamyl Carboxylase (GGCX) Mutation.

Congenital combined vitamin K-dependent clotting factors deficiency (VKCFD) is a very rare autosomal recessive bleeding disorder. Here we report a case of a girl with novel variant in the gamma-glutamyl carboxylase (GGCX) gene leading to VKCFD. A 3-month-old girl presented to our hospital with a history of bleeding from puncture site. Laboratory evaluation showed markedly prolonged partial thromboplastin time and activated partial thromboplastin time. Activities of vitamin K-dependent factors were all low. Genetic analysis revealed a homozygous currently unreported variant in the GGCX gene further supporting a diagnosis of VKCFD type 1. VKCFD due to GGCX mutation has an overall good prognosis.