A novel homozygous W99G mutation in CLDN-16 gene causing familial hypomagnesemic hypercalciuric nephrocalcinosis in Turkish siblings.

Alparslan C, Öncel EP, Akbay S, Alaygut D, Mutlubas F, Tatli M, Konrad M, Yavascan Ö, Kasap-Demir B. A novel homozygous W99G mutation in CLDN-16 gene causing familial hypomagnesemic hypercalciuric nephrocalcinosis in Turkish siblings. Turk J Pediatr 2018; 60: 76-80. Familial hypomagnesemic hypercalciuric nephrocalcinosis (FHHNC) (OMIM: 248250) is characterized by hypomagnesemia, hypercalciuria and nephrocalcinosis. FHHNC inevitably progresses to end-stage renal disease in decades. Mutations in CLDN-16 and CLDN-19 genes are associated with disrupted magnesium handling in the thick ascending limp of Henle`s loop. Patients with mutations in these genes share similar clinical features, and those with CLDN-19 gene mutations have ocular findings in addition. A 2-month-old boy, was admitted to our clinic with the complaints of upper respiratory tract infection. He was the first-born child of consanguineous parents. Laboratory findings revealed hypocalcemia and hypomagnesemia. Bilateral medullary nephrocalcinosis was detected on abdominal ultrasound. His ophthalmologic examination was unremarkable. With hypomagnesemia, hypercalciuria and nephrocalcinosis, the patient was considered to have FHHNC. Oral magnessium supplementation was initiated. Four years of follow-up has been completed uneventfully. When 6-days-old the brother of the case above was admitted with seizure. The patient was resistant to calcium and anticonvulsant drugs and the seizure activity could only be controlled after magnesium infusion. Biochemistry profile revealed hypocalcemia and hypomagnesemia. Urinary calcium extraction was 11 mg/kg/day. Medullary nephrocalcinosis was reported on renal ultrasound. His eye examination, echocardiography, transfontanel ultrasound and electroencephalography were normal. Due to the triad of hypomagnesemia, hypercalciuria and nephrocalcinosis, and the medical history of his elder brother, he was diagnosed with FHHNC. After correction of the electrolyte abnormalities, he was discharged from hospital and is currently being followed-up without any problem. In this manuscript, we shared our experience about a novel homozygous mutation (W99C) in CLDN-16 gene causing FHHNC in a couple of Turkish siblings.

Diagnostic value of urine soluble triggering receptor expressed on myeloid cells (sTREM-1) for late-onset neonatal sepsis in infected preterm neonates.

Objective Sepsis is a complex clinical condition caused by a dysregulated immune response to an infection resulting in a fatal outcome. This study aimed to investigate the value of urine soluble triggering receptor expressed on myeloid cells (sTREM-1) for diagnosing culture-proven sepsis in preterm infants. Methods Preterm neonates were evaluated for late-onset sepsis (LOS). Laboratory investigations were performed. Urine sTREM-1 samples and blood cultures were synchronously collected. Using blood culture results, preterm neonates were divided into the culture-proven group and suspected sepsis group. Results A total of preterm 62 infants were included in the study; 31 had culture-proven sepsis and 31 were suspected as having sepsis. There were no significant differences in gestational age, sex, birth weight, and delivery mode between the groups. Neonates in the culture-proven group had significantly higher urine sTREM-1 levels than did those in the suspected sepsis group. Using a cut-off point for a urine sTREM-1 level of 78.5 pg/mL, the sensitivity was 0.90, specificity was 0.78, positive predictive value was 0.68, and negative predictive value was 0.94. Conclusions The present study highlights the role of urine sTREM-1 levels in LOS. Urine sTREM-1 may be a reliable and sensitive marker in detecting sepsis in preterm infants.

Surfactant treatment for neonatal respiratory disorders other than respiratory distress syndrome.

BACKGROUND: It is suggested that there may be expanded use of surfactant replacement for the neonatal diseases such as meconium aspiration syndrome (MAS), pneumonia and possibly bronchopulmonary dysplasia (BPD). OBJECTIVE: To evaluate the characteristics and short-term outcome of the neonates given exogenous surfactant because of the diseases other than respiratory disease syndrome (RDS). METHODS: This retrospective study included 35 neonates admitted to the neonatal intensive care unit from January 2012 to December 2012 for an expanded use of surfactant. Data related to gestational age, birth weight, gender and perinatal risk factors were obtained from the patients' records. The short-term prognosis was also noted. RESULTS: The diagnosis was sepsis in 16 patients, eight MAS, seven transient tachypnea of the newborns (TTN) and four BPD. Mean gestational age was 35.6 ± 4.5 weeks and mean birth weight was 2661 ± 981 g. Of overall cases, 65% were boys and 35% girls. The mortality rate was 17%. Of six fatal cases, three was with BPD, two with sepsis and one with MAS. CONCLUSION: We think that surfactant replacement may be life saver in the neonatal diseases other than RDS such as BPD, MAS and sepsis by rapidly improving oxygenation. Further investigation is necessary to validate the significance of expanded use of surfactant.

Congenital hypothyroidism presenting with postpartum bradycardia.

Congenital hypothyroidism is a clinical condition characterized by lack of thyroid hormone because of thyroid gland developmental and thyroid hormone biosynthesis disorders. The most common cause of permanent hypothyroidism is congenital factors. Prompt diagnosis is critical. However, overt signs of hypothyroidism are rarely present at birth, and 95% of affected babies are asymptomatic. Hypoxemia, apnea, acidosis, increased intracranial pressure, vagal stimulus and central nerve system abnormalities represent the most common causes of bradycardia in the neonate. Bradycardia associated with congenital hypothyroidism is very rare. In this paper, a case of severe congenital hypothyroidism, induced by maternal blocker antibodies, who presented with bradycardia, is reported.

WITHDRAWN: TRANSIENT TACHYPNEA OF THE NEWBORN: A PREDICTIVE FACTOR FOR PROLONGED TACHYPNEA.

Ahead of Print article withdrawn by publisher.

Erythroid apoptosis in idiopathic neonatal jaundice.

OBJECTIVES: The objectives of this study were to evaluate the contribution of erythroid apoptosis to neonatal idiopathic pathologic jaundice and to determine whether a measurement of the erythroid apoptosis value at birth could predict the development of hyperbilirubinemia during the first 15 days of life. PATIENTS AND METHODS: Three groups were defined: group 1 (n = 101), healthy newborns whose erythroid apoptosis value and serum total bilirubin levels were detected from birth to day 15; group 2 (n = 24), newborns who were hospitalized for jaundice (serum total bilirubin level: > 12.9 mg/dL) without any identifiable pathologic cause; and group 3 (control group, n = 24), healthy newborns whose serum total bilirubin levels were < or = 12.9 mg/dL. Erythroid apoptosis value was assessed by flow cytometry using an annexin-V fluorescein isothiocyanate kit. RESULTS: In group 1, there was no correlation between the erythroid apoptosis value and serum total bilirubin levels obtained at birth and at the fourth and 15th days of life; the erythrocyte apoptosis value obtained at birth was not significantly different between the neonates whose serum total bilirubin levels were > 12.9 and < or = 12.9 mg/dL and who had prolonged and nonprolonged jaundice during follow-up. The erythroid apoptosis value differed significantly between the newborns in groups 2 and 3. There was no significant correlation between the erythroid apoptosis value and serum total bilirubin levels of the infants in groups 2 and 3. CONCLUSIONS: The erythroid apoptosis value obtained at birth could not predict the development of hyperbilirubinemia in neonates, but it was increased significantly in jaundiced neonates whose serum total bilirubin levels were > 12.9 mg/dL. In these infants, increase in the erythroid apoptosis value may be a result of the toxic effect of bilirubin or of a protective mechanism of neonates to increase heme turnover and bilirubin production to diminish oxidative stress.

Transient tachypnea of the newborn: predictive factor for prolonged tachypnea.

BACKGROUND: Because there is a lack of well-established criteria, the aim of the present paper was to determine risk factors to predict the duration of tachypnea in transient tachypnea of the newborn (TTN). METHODS: Data from 95 newborns with TTN were evaluated retrospectively. Clinical and laboratory findings were compared between patients in whom tachypnea lasted <72 h (group 1) or >72 h (group 2). RESULTS: Male gender, prematurity and delivery by cesarean section were the major risk factors for TTN. Parenteral furosemide had no effect on the clinical course. Peak respiratory rate (RRpeak) at the first 36 h was significantly higher in group 2 (P > 0.000). The cut-off for RRpeak during the first 36 h (RRpeak36) was 90/min and RRpeak36 > 90/min caused a 7.04-fold risk of prolonged tachypnea. White blood cell count and hematocrit levels were lower whereas duration of hospitalization and antibiotic treatment were longer in group 2. CONCLUSIONS: Assessment of RRpeak36 may be useful in predicting clinical course of TTN.

Hyperbilirubinemic serum is cytotoxic and induces apoptosis in murine astrocytes.

BACKGROUND: High levels of unconjugated bilirubin can be neurotoxic and gliotoxic. However, the effect of serum from patients with neonatal indirect hyperbilirubinemia on astrocyte viability has never been investigated. OBJECTIVES: In the present study, we searched for the possible toxic effect of hyperbilirubinemic serum on murine astrocytes. METHODS: Heat-inactivated patient serum was added to astrocyte cultures at different concentrations varying from 1 to 20%, and cultures were incubated for 24, 48, and 72 h. Sera from healthy infants without hyperbilirubinemia were used as controls. Cytotoxicity was evaluated according to the release of lactate dehydrogenase in the culture medium. Apoptotic cell death was determined by anti-single-strand DNA immunostaining. RESULTS: The results of the present study show that hyperbilirubinemic serum induces cytotoxicity and apoptotic astrocyte death in a concentration- and time-dependent manner. CONCLUSIONS: We conclude that serum from patients with neonatal indirect hyperbilirubinemia is cytotoxic to murine astrocytes.

Erythropoietin protects against necrotizing enterocolitis of newborn rats by the inhibiting nitric oxide formation.

BACKGROUND: Necrotizing enterocolitis (NEC) is an important neonatal disease with a high mortality rate; erythropoietin (Epo) is a hematopoietic growth factor. Functional Epo receptors are in the fetal and postnatal small bowel and their ligands are available for binding. Excessive nitric oxide (NO) production by an isoform of NO synthase inducible by inflammatory stimuli leads to changes in vascular permeability and tissue injury. The aim of this study was to investigate NO formation in an experimental model of NEC and the possible role of NO in the protection Epo provides against NEC. METHODS: Twenty-four Wistar albino rat pups were divided into three groups: group 1 = control; group 2 = hypoxia-reoxygenation and saline; group 3 = hypoxia-reoxygenation and recombinant human EPO (rhEpo) pretreatment. rhEpo was given 750 U/kg/week by intraperitoneal injection 3 times a week for 2 weeks. On the 15th day, hypoxia was induced by placing the pups in a 100% CO(2) chamber for 5 min. After the hypoxia period the pups were reoxygenated for 10 min with 100% O(2) and returned to their mothers. All pups were killed 4 h after the hypoxia-reoxygenation period was over. The abdomen was opened and representative samples of injured areas were taken for histopathologic examination. Then nitrite levels were determined in the intestine by Griess Reagent. RESULTS: On histopathological examination, injury scores in group-2 animals were found to be significantly higher than in group-3 animals (p = 0.001). Significantly increased intestinal nitrite levels were found in group-2 rats compared to the rats of groups 1 and 3 (p = 0.001 and p = 0.001, respectively). There was a positive correlation between the histological findings and the intestinal nitrite levels in group-2 and -3 animals (r = 0.94, p = 0.001; r = 0.99, p = 0.001, respectively). CONCLUSION: The present study demonstrates that the Epo-pretreated group had decreased levels of NO and limited mucosal necrosis in intestinal tissue samples. We believe that these results deserve further experimental studies in order to elucidate the possible effector mechanisms involved in the inhibitory relationship between Epo, NO and NEC.