Gonca Keskindemirci

A Case of Rhizomelic Chondrodysplasia Punctata in Newborn

Rhizomelic chondrodysplasia punctate (RCDP) is a rare autosomal recessive peroxisomal disease. The main features of the disease are shortening of the proximal long bones, punctate calcifications located in the epiphyses of long bones and in soft tissues around joints and vertebral column, vertebral clefting, dysmorphic face, and severe growth retardation, whereas cervical spinal stenosis may also rarely be present. Imaging of the brain and spinal cord in patients with this disorder may aid prognosis and guide management decisions. We report the newborn diagnosed as CDP with cervical stenosis. Our aim is to discuss current knowledge on etiopathogenesis as well as radiological and clinical symptoms of diseases associated with CDP.

Effects of selenium supplementation in the early stage of autoimmune thyroiditis in childhood: an open-label pilot study.

Abstract Aim: The aim of the study was to evaluate the role of selenium (Se) in childhood autoimmune thyroiditis regarding its effect on thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibody (TgAb), and thyroid morphology. Methods: Newly diagnosed 23 euthyroid children (mean age, 12.3±2.4 years) with Hashimoto thyroiditis (HT) received only 50 μg L-selenomethionine per day for 3 months. The baseline basal urinary iodine level, serum Se, TSH, fT4, TPOAb, and TgAb concentrations, and thyroid morphology by ultrasound were detected. We reanalyzed the TPOAb and TgAb changes at the 3rd month and then compared the thyroid morphology with 30 healthy individuals (mean age, 12.1±2.1 years) at the 6th month. Results: Serum TPOAb, TgAb, and thyroid echogenicity were unchanged with Se supplementation. A prominent decrease in thyroid volume was noteworthy; 35% of patients showed a thyroid volume regression rate of ≥30%. Conclusion: In terms of TPOAb and TgAb, Se may not benefit in the euthyroid period of HT, but Se supplementation seems to lead a favorable response in thyroid volume regression.

HAX-1 deficiency: Characteristics of five cases including an asymptomatic patient.

BACKGROUND Mutations in the HAX-1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN), which particularly manifests with recurrent skin, lung and deep tissue infections from the first few months of life. OBJECTIVE We retrospectively evaluated the clinical and laboratory findings of the patients diagnosed with SCN carrying HAX1 gene mutations. METHODS A total of five patients with SCN, carrying a HAX1 gene mutation, were evaluated in terms of clinical and laboratory findings. Mutation analysis of the candidate genes (HAX1, ELANE and CSF3R) was performed. RESULTS All of the patients lived in Turkey; four of them were of Kurdish origin and one was Turkish. Of the five patients, three were girls and two were boys, and the mean age of the patients was 8.8 years old (range 4-15 years). The mean age of diagnosis was 25.8 months (range 2 months-5 years). The infections diagnosed included recurrent gingivitis, stomatitis, and skin and soft tissue abscesses. Developmental retardation and epilepsy were present in only one patient, whereas speech retardation was present in two. All of our patients had a HAX1 mutation, and are still alive and none of them has shown malignant transformation yet. CONCLUSION Complete blood count should be performed and absolute neutrophil count should be evaluated in patients with recurrent severe infections. In the event that neutropenia is detected, they should be investigated in terms of SCN and mutation analysis should be performed.

Cochlear functions in children with familial Mediterranean fever: any role of the severity of the disease?

OBJECTIVES The aim of the study was to compare the cochlear functions of children diagnosed with familial Mediterranean fever (FMF) with healthy controls and to determine their cochlear functions according to their disease severity. METHODS Seventy-three children with FMF and 30 healthy controls were included in the study. All the patients and controls were evaluated by audiologic evaluation, including high-frequency pure-tone audiometry and distortion product otoacoustic emission tests (DPOAE). The disease severity was evaluated by scoring systems adapted from those used by Pras et al. and with severity scoring systems from the Sheba Medical Center. RESULTS High-frequency pure-tone audiometry and DPOAE levels were normal in both patients and controls. Significant differences in the hearing levels of FMF patients were not found, according to both adapted severity scoring systems. CONCLUSIONS Cochlear functions in children with FMF had been evaluated by previous studies, but in our study we evaluated hearing functions according to both controls and disease severity. As a unique study comparing cochlear functions according to severity scores, no significant differences were shown between the groups and controls.

Novel Mutation in CECR1 Leads to Deficiency of ADA2 with Associated Neutropenia

PurposeAdenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2.MethodsWe reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives.ResultsGenetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives.ConclusionThis is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.

Coexistence of early onset sarcoidosis and partial interferon-γ receptor 1 deficiency

Pediatric sarcoidosis comprises a spectrum of childhood granulomatous inflammatory conditions. Pathological hallmark of the disease is granuloma formation that is seen in the affected tissues and almost any organ or system can be involved. There are two forms of pediatric sarcoidosis. One is seen in older children and the clinical picture is very similar to that of adult sarcoidosis and the other one is seen in early childhood. Sarcoidosis in early childhood can be divided as Blau syndrome (familial form) and early onset sarcoidosis (sporadic form). In both of the diseases there is a defect in the NOD2/CARD15 gene. The typical triad of early onset sarcoidosis is polyarthritis, dermatitis and uveitis. Interferon-γ receptor 1 deficiency is caused by defects in the IFNγR1 gene and non-tuberculosis mycobacterial pathogens are the leading causes of infections that start in early childhood. Herein we report a patient who presented with the symptoms of early onset sarcoidosis and also had partial interferon-γ receptor 1 deficiency that presented with BCG-osis. In addition to anti-mycobacterial treatment, methotrexate and prednisolone were used in therapy.

How do we encounter rare factor deficiencies in children? Single-centre results from Turkey.

BackgroundRare factor deficiencies (RFDs) are autosomal recessively inherited coagulation factor deficiencies encountered at a frequency of between one in 500 000 and one in two million. Materials and methodsOne hundred and ninety-two patients, diagnosed as having RFD, followed and treated in our clinic between 1990 and 2013 were retrospectively evaluated in this study. ResultsFrom the 192 patients, 142 had FVII, 15 had FX, 14 had FXI, 10 had fibrinogen, six had FV, two had FXIII, two had FV + FVIII and one had FII deficiency. One hundred and thirty of the cases were boys and 62 were girls. The age range was 2 weeks to 24 years and the ages at the admission were between 2 weeks and 16 years. The rate of consanguinity was 49.4%. Eighty-eight of our patients were asymptomatic (45.8%) and 104 were symptomatic (54.2%). Asymptomatic patients were diagnosed by family histories (39.8%), preoperative laboratory studies (54.6%) and operational bleeding (5.6%). Sixty-eight of our symptomatic patients displayed grade II (65.4%) and 36 displayed grade III bleeding symptoms (34.6%). First bleeding regions were skin (33%), nose (28%), central nervous system (CNS) (15.5%), oral cavity (10.5%), soft tissue (6%), joint (3%), urinary system (2%) and gastrointestinal system (GIS) (2%), respectively. The bleeding prevalence rates of our symptomatic patients are listed as epistaxis 62.5%, skin bleedings 53%, oral cavity bleeding 28.8%, haematomas 18.3%, CNS bleedings 17.3%, haemarthrosis 14.4%, GIS bleedings 3.8%, menorrhagia 2.9%, haematuria 1.9%, bleeding because of operations 1.9% and iliopsoas bleedings 1.9%. CNS bleedings (41%) take the first place among the serious bleedings of our cases, followed by haemarthrosis (36.4%), GIS bleedings (18.1%) and iliopsoas bleedings (4.5%). Prophylaxy was applied to nine patients (five patients with FVII, two patients with fibrinogen and one each with FV and FX deficiency). ConclusionsThe characteristics of clinical presentations, first bleeding attacks, bleeding prevalence and severe bleedings as well as prophylactic approaches are discussed in this article.

Familial Mediterranean Fever: Diagnosing as Early as 3 Months of Age

Familial Mediterranean Fever is an autosomal recessive disease. Major symptoms of disease are recurrent fever accompanied by serositis attacks. The disease is usually diagnosed before 20 years of age. Symptoms related to FMF are noted when children become more verbal, usually after 2 years of age. In this case report, the youngest patient with the diagnosis of FMF is presented. She was consulted to pediatric rheumatology for the high acute phase response and fever. It was learned that her mother had recurrent swelling of her ankle joints. Mutation analysis was performed and two homozygous mutations (M694V and R202Q) were identified. She was diagnosed as FMF at 3 months of age and colchicine was started. She responded to colchicine. Her uncontrolled acute phase response declined gradually. This case was reported to point out the importance of early remembrance of autoinflammatory diseases even at very early ages especially at endemic countries.

Miliaria rubra and thrombocytosis in pseudohypoaldosteronism: case report.

Pseudohypoaldosteronism type 1 (PHA1) is a disease involving a state of renal tubular unresponsiveness to the action of aldosterone and characterized by excessive salt loss in the urine, hyperkalemia, and metabolic acidosis. In kidney, PHA1 may occur primarily by mutations in the subunits of the sodium channel or in the mineralocorticoid receptors, and secondarily by several renal disorders. Miliaria rubra and thrombocytosis are reported in a 6-month-old girl with PHA1. In patients with PHA1, miliaria rubra-like cutaneous eruptions are suggested to occur due to obstruction of eccrine sweat glands through inflammation caused by excessive sodium excretion in sweat during hyponatremic crises. The presence of thrombocytosis in patients with PHA1 has not been previously reported. A hypothesis is proposed suggesting that sympathetic activation which provides vascular tonus during sodium excretion in sweat and salt-depletion crisis may play a role in the development of eruptions and thrombocytosis in patients with PHA1.

Does Familial Mediterranean Fever Affect Cognitive Function in Children? Electrophysiological preliminary study

ABSTRACT Objectives: Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease with subclinical inflammation occurring between attacks. The aim of the study was to prospectively evaluate the cognitive function of children diagnosed with FMF that were under colchicine therapy and compare them with healthy controls through electrophysiologically event-related potentials (ERPs) study. Methods: Twelve children with FMF and 12 healthy controls were included in the study. During the electroencephalography recordings, all participants were instructed to discriminate rare stimuli (target stimuli) from frequent stimuli (standard stimuli) by pressing a botton on a mouse immediately following the target stimulus. P300, the cognitive component of ERP, was obtained in response to target stimuli and its amplitude and latency were measured. Results: The amplitude of the P300 of the FMF patients was higher and the latencies of the P300 of the FMF patients were shorter than the amplitudes and latencies of control patients, respectively. The difference between the groups was statistically significant for amplitude but not for latency. Conclusions: Cognitive processing reflecting allocation of attention and visual processing speed seems not to be negatively affected in FMF patients with homozygous M694V mutations undergoing colchicine treatment. As this study is unique in its evaluation of the cognitive function of children with FMF, these findings may be helpful for counseling families and patients affected by the condition.