Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare, fatal, multisystem disorder that mainly effects the liver, kidney, skin, central nervous and musculoskeletal systems. This progressive disorder has autosomal recessive inheritance and is commonly caused by a mutation in the vacuolar protein sorting 33B (VPS33B) gene on chromosome 15q26.1. 1 This syndrome is also caused by a mutation in VIPAR (also called C14ORF133) in individuals with ARC syndrome without VPS33B defects. 2 Additional clinical features of the disease are ichthyosis, platelet abnormality, agenesis of the corpus callosum, congenital cardiovascular anomalies, deafness, recurrent sepsis, hypothyroidism and nephrogenic diabetes insipidus. 3Herein, we report a female newborn with ARC syndrome caused by a homozygous mutation in VPS33B [IVS1-2A>C (c.97-2A>C)] gene. Case ReportA 14-day-old female neonate was admitted to the neonatal intensive care unit with jaundice. She was born at 40 th week of gestation via caesarean section with a birth weight of 3,360 g. Her parents were cousin. On physical examination; dysmorphic features [low set ear, high arched palate, beaked nose, micrognathia, rigid kyphosis (Fig. 1a), radial deviation of the wrist (Fig. 1b), flexion contracture of the left elbow, talipes calcaneovalgus (Fig. 1c)], heart murmur, jaundice, dry and scaly skin like ichthyosis, and hepatomegaly were noted.On laboratory examination, hemoglobin was 12.2 g/dl, leucocytes counts 11,000/mm 3 and platelet counts 331,000/mm 3 . Review of a peripheral blood smear revealed large and pale platelets (Fig. 2). Activated partial thromboplastin time, prothrombin time and international normalized ratio were 25.6 secs (23.6 -34.8), 13 secs (11 -15.5) and 1.04 (0.8 -1.25), respectively. Bleeding time was 14 minutes. Platelet aggregation showed abnormal responses to epinephrine and adenosine diphosphate (ADP) but normal responses to collagen and ristocetin.

Objective The study aimed to analyze the risk factors and clinical features of metabolic bone disease of prematurity (MBDP) in premature infants compared with infants of similar gestational age and birthweight without MBDP. Study Design This retrospective case–control study was performed by comparing 81 cases of MBDP with 63 controls to identify potential risk factors. Premature infants with a gestational age ≤33 weeks and birthweight <1,500 g were included. Medical records were examined in terms of maternal conditions, potential risk factors, and clinical characteristics. Results Bone fractures and invasive ventilator dependence were the most common clinical features of MBDP. Duration of invasive ventilation and total mechanical ventilation days, necrotizing enterocolitis, corticosteroid use, anticonvulsive drug use, duration of dexamethasone and caffeine use, total parenteral nutrition, and length of hospitalization were significantly higher in neonates with MBDP (p < 0.05). Breastfed neonates and those receiving human milk fortifier had a lower incidence of MBDP than those premature formula or mixed feeding (p < 0.05). Anticonvulsive drug use (odds ratio: 2.935; 95% confidence interval: 1.265–6.810) was identified as a risk factor for MBDP at multiple regression analysis. Conclusion Our results show that anticonvulsive drug use is a significant risk factor for the development of MBDP. If long-term use is not required, anticonvulsive drugs should be stopped as soon as possible. Further studies involving patients with MBDP are required to determine the risk factors and clinical features. Key Points

Digoxin is widely used in the treatment of congestive heart failure and some arrhythmias. Digoxin toxicity may occur easily because digoxin has a narrow therapeutic index. This retrospective study was conducted to evaluate the clinical signs and symptoms of toxic serum digoxin levels in neonates. Medical reports of the neonates who had serum digoxin concentrations >2 nanogram/milliliter (ng/ml) were reviewed in terms of patient demographics, serum digoxin concentrations, signs and symptoms of digoxin toxicity, serum digoxin and electrolyte levels, renal function tests, electrocardiograms, echocardiography, and treatments applied. Digoxin toxic levels were identified in the 13 neonates. Of the 13 neonates with digoxin toxic level, 9 (69%) were term and 8 (62%) were female. Twenty-three percent (3/13) of newborn infants were symptomatic. Symptomatic patients had statistically significantly higher serum digoxin levels, at 7.76±2.76 (5.4-10.8) ng/ml, than asymptomatic patients, at 3.31±1.09 (2.02-4.95) (p=0.036). Symptoms related to toxic digoxin levels were observed in the three neonates with plasma digoxin levels >5 ng/ml. Gastrointestinal and central nervous system symptoms were the major clinic findings. Despite high digoxin levels, no digoxin-related arrhythmia was observed on electrocardiography, other than sinus bradycardia. Two premature neonates were treated with digoxin-specific antibody Fab fragments (DigiFab ®) and hypokalemia developed in both of them. Our data suggests that symptoms related with digoxin toxic levels were observed in neonates with plasma digoxin levels >5 ng/ml. Serum digoxin levels should be measured in case of signs and symptoms of digoxin toxicity or risk factors for such toxicity.

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