Yakup Aslan

CEP152 is a genome maintenance protein disrupted in Seckel syndrome

Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation.

Mutations in RIPK4 Cause the Autosomal-Recessive Form of Popliteal Pterygium Syndrome

The autosomal-recessive form of popliteal pterygium syndrome, also known as Bartsocas-Papas syndrome, is a rare, but frequently lethal disorder characterized by marked popliteal pterygium associated with multiple congenital malformations. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this malformation syndrome to chromosomal region 21q22.3. Direct sequencing of RIPK4 (receptor-interacting serine/threonine kinase protein 4) showed a homozygous transversion (c.362T>A) that causes substitution of a conserved isoleucine with asparagine at amino acid position 121 (p.Ile121Asn) in the serine/threonine kinase domain of the protein. Additional pathogenic mutations-a homozygous transition (c.551C>T) that leads to a missense substitution (p.Thr184Ile) at a conserved position and a homozygous one base-pair insertion mutation (c.777_778insA) predicted to lead to a premature stop codon (p.Arg260ThrfsX14) within the kinase domain-were observed in two families. Molecular modeling of the kinase domain showed that both the Ile121 and Thr184 positions are critical for the proteins stability and kinase activity. Luciferase reporter assays also demonstrated that these mutations are critical for the catalytic activity of RIPK4. RIPK4 mediates activation of the nuclear factor-κB (NF-κB) signaling pathway and is required for keratinocyte differentiation and craniofacial and limb development. The phenotype of Ripk4(-/-) mice is consistent with the human phenotype presented herein. Additionally, the spectrum of malformations observed in the presented families is similar, but less severe than the conserved helix-loop-helix ubiquitous kinase (CHUK)-deficient human fetus phenotype; known as Cocoon syndrome; this similarity indicates that RIPK4 and CHUK might function via closely related pathways to promote keratinocyte differentiation and epithelial growth.

Plasma Soluble Interleukin-2 Receptor Levels in Patients With Idiopathic Thrombocytopenic Purpura

Soluble interleukin‐2 receptor (sIL‐2R) was measured in the plasma of 31 patients with idiopathic thrombocytopenic purpura (ITP) and 22 normal controls. When thrombocytopenia persisted longer than 6 months, the diagnosis of chronic ITP was made. Twenty patients had acute ITP, 11 patients had chronic ITP, and all patients received high‐dose methylprednisolone (HDMP) (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days). The sIL‐2R levels of the patients were determined before being giving HDMP and 14 days after the end of HDMP therapy. Platelet counts were determined before administration of HDMP, one day after the end of HDMP therapy, and once every 28 days for 7 months thereafter.

Adrenal hemorrhage in newborns: a retrospective study.

BackgroundAdrenal hemorrhage (AH) is a relatively uncommon condition in neonates. This study aimed to review the clinical, laboratory and ultrasonographic findings of AH in newborns.MethodsThe medical records of 13 newborns with AH who had been admitted to our neonatal intensive care unit were retrospectively reviewed.ResultsOf the 13 newborns with AH, 8 (62%) were term and 10 (77%) were male babies. Clinical presentations included neonatal jaundice (85%), paleness and/or flank mass (38%), discoloration of the scrotum (15%), and hypotonia/lethargy or hypotension (8%). Five newborns had anemia and four had adrenal insufficiency. Adrenal insufficiency was observed in 80% of the premature infants with AH. AH occurred on the right side in 9 patients (69%). The most predisposing cause of AH was disseminated intravascular coagulation secondary to sepsis or perinatal hypoxia in preterm infants, and large for gestational age in term infants. Ultrasonography (USG) revealed a hypoechoic mass in 7 newborns (54%), a mixed solid-liquid mass in 5 (38%), and an echogenic mass (8%) in 1. Hemorrhage disappeared within 8.6±4.5 (4–16) weeks.ConclusionsAH occurs in the newborns with unexplained jaundice. Adrenal insufficiency is more frequent in preterm than in mature infants. Abdominal USG is required to determine AH in a newborn with swelling and bluish discoloration of the scrotum. Serial USG is the best modality for monitoring AH to prevent unnecessary surgery.

Autosomal recessive multiple pterygium syndrome: a new variant?

Multiple pterygium syndromes include at least 15 different entities characterized by multiple pterygia or webs of the skin and multiple congenital anomalies. We describe a female infant who presented with a distinct constellation of multiple anomalies consisting of pterygia of the inguinal, intercrural and popliteal areas, flexion contractures and arthrogryposis of some joints, craniofacial anomalies including ectropion, medial canthal web, blepharophimosis, hypoplasia of nose, oral and nasopharyngeal cavities, vocal cords and tongue, micrognathia, orolabial synechiae secondary to pterygia, low set ears, alopecia, sad and expressionless face, short neck, asymmetric nipples, anal stenosis, rectal polyp, hypoplastic labia majora, complete syndactyly of all fingers and toes, pes equinovarus, bandlike web between feet, and absence of the nails and phalangeal-palmar creases. Radiological examination showed synostosis, absence or hypoplasia of metacarpal, metatarsal and phalangeal bones on feet and hands, and hypoplasia of pelvic bones and scapulae. This pattern of anomalies does not fit entirely any of the known multiple pterygium syndromes. Autosomal recessive inheritance is most likely due to the presence of three similarly affected siblings and normal parents.

The role of high dose methylprednisolone and splenectomy in the accelerated phase of Chédiak-Higashi syndrome

The Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disorder. Some cases with CHS develop the accelerated phase characterized by pancytopenia, high fever and lymphohistiocytic infiltration of liver, spleen and lymph nodes. The treatment of the accelerated phase of CHS is difficult. We describe a case with CHS in the accelerated phase who had multiple polyposis and pulmonary infiltration that was probably due to involvement of CHS. She was successfully treated with high-dose methylprednisolone at her first admission. At her second admission, splenectomy was performed to remove hypersplenism, and her clinical, radiological and hematological findings improved significantly.

Reference intervals for thyrotropin and thyroid hormones and ultrasonographic thyroid volume during the neonatal period

Objective. To determine thyrotropin (TSH) and thyroid hormones reference ranges in healthy term newborns during the neonatal period and to assess the ranges of thyroid volume in newborns using ultrasound scanning. Methods. Blood samples were collected from 296 healthy newborns at birth (cord; n: 47) and before feeding on the 1st, 3rd, 5th, 7th, 10th, 14th, and 28th days of life. The levels of TSH and thyroid hormones of the newborns were then compared with results from 50 healthy adults. Thyroid ultrasonography (USG) was performed by the same radiologist on 38 newborns aged 10 days. Results. TSH and thyroid hormone levels in newborns were statistically higher than those in adults for each day (p < 0.001). Serum TSH concentration on the 1st day of life was higher than at other times (p < 0.001). Mean TSH concentration reverted to the cord level at the 5th or 7th day of life (p > 0.05). TSH levels were no higher than 10 mIU/ml after 2 weeks postnatal age. There was no correlation between hormone levels and Ponderal index (PI), birth weight, gender, or delivery type. Mean thyroid volume was 0.72 ± 0.24 ml (0.36–1.62 ml). Conclusions. We conclude that our results are important for CH screening regarding time-dependent changes of TSH and thyroid hormones besides diagnosis of thyroid hypoplasia or hyperplasia.

Risk factors and clinical characteristics of Stenotrophomonas maltophilia infections in neonates

BACKGROUND The aim of this study was to review the risk factors and clinical, bacteriological, and epidemiological characteristics of Stenotrophomonas maltophilia infections in our neonatal intensive care unit. METHODS A retrospective matched case-control study was performed by comparing 23 cases of S maltophilia with 45 controls to identify the potential risk factors. To identify the case patients, the admission and medical records of patients in the neonatal intensive care unit and records from the Microbiology Department were reviewed between 2003 and 2008. RESULTS Sepsis in two neonates (9%), conjunctivitis in two neonates (9%), and ventilator-associated pneumonia in 19 (82%) neonates were determined. Invasive-procedures, exposure to aminoglycoside and carbapenem, total parenteral nutrition, histamine 2 blockers, exposure to steroids, cholestasis, and duration of hospitalization were significantly associated with S maltophilia infections (p<0.05). On multivariate analysis, invasive procedures (odds ratio, 18.81) and duration of hospitalization (odds ratio, 1.06) were determined to be the risk factors for S maltophilia infection. The most active antimicrobial agent was trimethoprim/sulfamethoxazole (87%) for S maltophilia infection, and the mortality rate was 17%. CONCLUSIONS Neonatologists should avoid from unnecessary invasive procedures and broad-spectrum antibiotics to reduce S maltophilia infections. Invasive procedures should be finished in the shortest time possible. Agent/factor-specific antibacterial treatment should be administered. Patients being discharged as early as possible will also reduce infection frequency. Stenotrophomonas maltophilia should be considered in patients with high Stenotrophomonas infection risk factors.

Henoch-Schonlein purpura in north-eastern Turkey

Abstract Aim: To evaluate the epidemiological and clinical findings in children with Henoch-Schönlein purpura (HSP) admitted during a 10-year period, 1995 to 2004, and to compare them with series from other parts of the world. Methods: The medical records of all children aged 17 years or less admitted with a diagnosis of HSP to the Department of Pediatrics of Karadeniz Technical University were evaluated retrospectively for epidemiological and clinical features. Results: Of 116 children, 73 (63%) were boys. The mean (SD) age at presentation was 8.9 (3.7) years and one-third of them were older than 10 years of age. Over half the cases presented between September and January. All patients had the typical skin rash. Gastro-intestinal manifestations were seen in 64 (55.1%) and joint manifestations, common during the early course of the disease, in 73 (62.9%). Two patients required laparatomy, one for acute abdomen and the other for bowel resection owing to intussusception. Renal manifestations were observed in 36 (31%), all within 3 months of initial symptoms, and one patient (0.8%) with nephritic syndrome progressed to end-stage renal disease. Five patients had hypertension without urinary findings. Symptoms recurred in eight patients (6.9%) over a period ranging from 2 to 5 months after complete resolution of symptoms. There was a history of a preceding upper respiratory tract infection in 16 (13.7%) and a streptococcal infection was confirmed by throat culture in 12 of the 42 (28.5%) children at presentation. Conclusion: HSP is generally benign and self-limiting. Hypertension may be seen during the course of the disease without urinary findings. In this area, it seems to affect older children and there is a relatively lower incidence of renal manifestations.

Intravenous Amiodarone Used Alone or in Combination With Digoxin for Life-Threatening Supraventricular Tachyarrhythmia in Neonates and Small Infants

Objectives: The purpose of this study was to report the efficacy of intravenous amiodarone alone or in combination with digoxin in neonates and small infants with life-threatening supraventricular tachyarrhythmia (SVT). Methods: We retrospectively analyzed 9 neonates and small infants with life-threatening or resistant SVT who were treated with intravenous amiodarone alone or in combination with digoxin. Results: This report consists of 8 patients with reentrant SVT and 1 with atrial flutter. On admission, 7 patients had a congestive heart failure and 3 of whom had cardiovascular collapse. Intravenous rapid bolus of adenosine caused a sustained sinus rhythm in 4 patients. These patients were given digoxin initially, but recurrence of persistent tachyarrhythmia necessitated the use of intravenous amiodarone in all these patients. Amiodarone was given initially to the other 4 patients in whom adenosine caused only temporary conversion to the sinus rhythm. It was effective in 2 patients. In the other 2, digoxin was added to therapy for tachycardia control. Amiodarone alone or in combination with digoxin effectively controlled reentrant SVT in all patients. This combined treatment caused ventricular rate control in patient with atrial flutter, and conversion to the stable sinus rhythm was achieved at approximately 8 months. Conclusions: Intravenous amiodarone alone or in combination with digoxin was found to be safe and effective in controlling refractory and life-threatening SVT in neonates and small infants.