Fatma Çakmak Çelik

Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome

Arthrogryposis–renal dysfunction–cholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apical–basolateral polarity regulator (VIPAR). Cardinal features of ARC include congenital joint contractures, renal tubular dysfunction, cholestasis, severe failure to thrive, ichthyosis, and a defect in platelet alpha‐granule biogenesis. Most patients with ARC do not survive past the first year of life. We report two patients presenting with a mild ARC phenotype, now 5.5 and 3.5 years old. Both patients were compound heterozygotes with the novel VPS33B donor splice‐site mutation c.1225+5G>C in common. Immunoblotting and complementary DNA analysis suggest expression of a shorter VPS33B transcript, and cell‐based assays show that c.1225+5G>C VPS33B mutant retains some ability to interact with VIPAR (and thus partial wild‐type function). This study provides the first evidence of genotype–phenotype correlation in ARC and suggests that VPS33B c.1225+5G>C mutation predicts a mild ARC phenotype. We have established an interactive online database for ARC (https://grenada.lumc.nl/LOVD2/ARC) comprising all known variants in VPS33B and VIPAR. Also included in the database are 15 novel pathogenic variants in VPS33B and five in VIPAR. Hum Mutat 33:1656–1664, 2012.

Simplified gyral pattern with cerebellar hypoplasia in Sedaghatian type spondylometaphyseal dysplasia: A clinical report and review of the literature†

We report on a patient with Sedaghatian type spondylometaphyseal dysplasia (SSMD) who presented with metaphyseal dysplasia, congenital atrioventricular block, simplified gyral pattern, hypogenesis of corpus callosum, and severe cerebellar hypoplasia. We want to emphasize that in this rare congenital lethal skeletal dysplasia with unknown etiology, central nervous system malformations might be a major component of the disorder and should be evaluated in detail to possibly uncover the underlying pathophysiology.

Two cases of fetus in fetu

Fetus in fetu (FIF) is a rare cause of abdominal mass in children. One of the malformed monozygotic diamniotic twins is located in the body of other twin. It is differentiated from teratoma by the presence of vertebral organization with limb buds and other organ systems. Diagnosis is based on radiologic findings. Surgical excision is the treatment of choice, leading to the complete removal of the mass. To our knowledge, less than 200 cases have been described in the literature. Herein, we report 2 cases of FIF, a newborn who was diagnosed antenatally and a three-and-half-year- old boy diagnosed with mediastinal FIF after admission for recurrent respiratory tract infections.

Maternal and neonatal outcomes in advanced maternal age: a retrospective cohort study

Abstract Objectives: To describe the effect of extremely advanced maternal age (EAMA) on maternal/neonatal outcomes. Methods: This was a case-control study in which 127 women ≥40 years at the time of delivery out of 2853 singleton hospital deliveries in Ondokuz Mayis University between 1 January 2008 and 31 August 2010 constituted the study group. One hundred and twenty-seven else were chosen randomly out of 2412, 21–35 years old women, via a computer system as controls. Demographic features of 254 mothers and infants as well as maternal and neonatal complications were recorded. Results: Mean maternal age was 41.5 ± 1.9 (40–49) years in EAMA group and 28.9 ± 4.2 (21–35) years in controls. Primigravidity was 19.6% in the EAMA group, whereas 37.8% in controls (p = 0.003). No difference was found between groups according to route of delivery, stillbirth, preterm birth, congenital abnormalities, gender of babies, NICU admission and respiratory problems (for all p > 0.05). A 5th min Apgar score <7 was more frequent in babies born to EAMA mothers compared to controls (9.8% versus 4.9%, p = 0.004). Conclusion: The present study shows that EAMA mothers and their offsprings have similar peri and neonatal risks compared to younger mothers, except lower 5th minute Apgar scores. We conclude that with good perinatal care, EAMA women and their babies can pass through the perinatal period with similar risks of younger women.

A boy with trisomy 13 presenting with a subtle clinical picture and metopic synostosis.

A Boy With Trisomy 13 Presenting With a Subtle Clinical Picture and Metopic Synostosis Sevim Unal, Fatma Cakmak Celik,* Derya Soy, Serdar Ceylaner, and Gulay Ceylaner Neonatology Department, Republic of Turkey Ministry of Health Ankara Diskapi Children’s Health Training and Research Hospital, Diskapi, Ankara, Turkey Department of Pediatrics, Republic of Turkey Ministry of Health Ankara Diskapi Children’s Health Training and Research Hospital, Ankara, Turkey Intergen Genetics Center, Ankara, Turkey

Assessment of different folic acid supplementation doses for low-birth-weight infants.

AIM The adequacy of 50 mcg folic acid supplementation given to low-birth-weight babies was investigated. The folate levels of the mothers and infants, and breastmilk, and the optimum dose for folic acid supplementation were also investigated. MATERIAL AND METHODS After obtaining blood from 141 low-birth-weight infants on the 1st day of life for serum and red cell folate levels, the infants were randomly allocated into three groups according to the folic acid supplement dose. Forty-six infants were given 25 μg/d folic acid, 39 were given 50 μg/d folic acid, and 44 were given 75 μg/d folic acid. Folic acid could not be given to 12 infants. Follow-up blood samples were obtained at the end of folic acid supplementation. Maternal samples for red cell and serum folate levels and breast milk folate levels were obtained within the first 48 hours and the samples for measuring breastmilk folate level were obtained on the 3rd day postnatally. The feeding modes of the infants, maternal folic acid intake, and details of neonate intensive care unit course were recorded. RESULTS The mean birth weight and gestational age of the infants were found as 1788.2±478.4 g and 33.5±2.9 weeks, respectively. The mean serum and red cell folate levels on admission were found as 21.2±12.2 ng/mL and 922.7±460.7 ng/mL, respectively. The mean maternal serum and red cell folate levels and the mean breast milk folate levels were found as 12.3±7.5 ng/mL, 845.5±301.4 ng/mL, and 30.6±33.0 ng/m, respectively. The breast milk folate levels of mothers who were supplemented with folic acid during pregnancy were significantly higher compared with mothers who were not supplemented with folic acid (p<0.001). Infants who were supplemented with folic acid had higher follow-up serum folate levels compared with the basal level in all groups, but there was no statistically significant difference between the groups. CONCLUSION This study showed that the folic acid doses of 25, 50, and 75 μcg/d affected serum folate levels similarly. We can conclude that the dose of 25 μcg/d is adequate for low-birth-weight infants.

Pilor atrezisi ve epidermolizis bülloza birlikteliği: İki olgu sunumu ve literatür derlemesi

The coexistence of pyloric atresia (PA) and epidermolysis bullosa (EB) is a rare but well-known surgical emergency in neonates. PA/EB is described by the association of atresia of the pylorus and bullous lesions on the skin. Ninety one cases have been reported in the literature to date. We present two new cases and evaluate the association of PA/ EB, its etiopathogenesis and the clinical properties. Case 1: A three-day-old female presented with nonbilious vomiting and bullous lesions 2-3 cm in diameter on the extremities. Abdominal X-ray showed a single air-fluid level in the left upper quadrant. At laparotomy, we found PA and performed a pyloro-pylorostomy. The patient died due to sepsis complication of EB two months after surgery. Case 2: A two-day-old male presented with severe dermal bullous lesions on the trunk, neck and extremities. His stomach was dilated and there was no gas distally. We found PA and performed gastroduodenostomy. Initially, he tolerated the feeding well, but he died due to severe sepsis on the postoperative 23rd day. Almost all neonates born with the PA/EB result in a fatal outcome in the first few years. The complications related to EB are usually the cause of death. Even after successful repair of PA, skin lesions lead to death due to infection.

A newborn with antenatal testis tortion

Testis tortion in the newborn (especially antenatal testis tortion) is observed very rarely and constitutes 10-12% of childhood testis tortions. In testis tortion, firm and painless testicular tissue is palpated on physical examination. Doppler ultrasonography is a sensitive method in the diagnosis. In cases of neonatal testis tortion, the testis can be saved with appropriate surgical exploration in only 0-5% of the cases. Here, a newborn with antenatal testis tortion who underwent orchiectomy in the first day of life was presented.

An unusual form of Gaucher’s disease: pulmonary and cardiovascular involvement and cholelitiasis

Gaucher’s disease is an inherited storage disease caused by a deficiency of the enzyme glucocerebrosidase. Although the hepatic manifestations are seen frequently, pulmonary and cardiovascular involvements are known to be very rare in Gaucher’s disease. This report presents these rare findings made by conventional radiography, computerized tomography (CT), and High-resolution CT (HRCT) of a 16-year-old female patient with fatal Gaucher’s disease.