Eda Özaydin

Valproate-Associated Coagulopathies in Children During Short-Term Treatment

Valproic acid is one of the most frequently prescribed antiepileptic drugs for the therapy of generalized and focal epilepsies. Valproate induces a variety of hemostatic disorders such as thrombocytopenia, abnormal platelet function, hypofibrinogenemia, and decreased concentrations of von Willebrand factor, and it rarely causes serious bleeding complications. It may also lead to atherosclerosis and thrombosis. However, there is still lack of knowledge about the incidence and occurrence of these particular side effects. In this prospective systematic study, we assessed the early effects of sodium valproate on both pro- and anticoagulatory factors, homocysteine, and lipoprotein (a) in 24 newly diagnosed epileptic children treated with valproate. Valproate causes decreased factor VII levels, platelet count, factor VIII, Protein C, fibrinogen, and increased lipoprotein (a) levels. To the best of our knowledge, our report is the first in the medical literature, which describes that valproate significantly reduces factor VII levels even during short-term therapy.

Mucocele of the anterior lingual salivary glands: from extravasation to an alarming mass with a benign course

Mucoceles are common cystic lesions in the oral cavity. However, mucoceles located on the ventral surface of the tongue originating from anterior lingual salivary glands are rare. Only 24 cases were reported in the medical literature, of which most were relatively small lesions measuring less than 20 mm in diameter. This report describes a large-sized mucocele of the anterior lingual salivary glands in an 8-year-old boy who was treated by surgical excision of the lesion. The authors emphasize the importance of preoperative awareness and en bloc excision of the lesion even in asymptomatic patients to avoid further enlargement and complications.

Differences in iron deficiency anemia and mean platelet volume between children with simple and complex febrile seizures

OBJECTIVE The relationship between iron deficiency anemia and febrile seizures (FSs) were examined in several studies before. The aim of our study is to find out the differences regarding iron deficiency anemia, demographic characteristics and mean platelet volume (MPV) which is an inflammatory marker between simple and complex febrile seizure groups. METHODS In this study, the authors investigated the recordings of 493 children with a diagnosis of simple and complex febrile seizure, aged between 6 months and 6 years, followed between 2002 and 2010 retrospectively. RESULTS Mean age and male/female ratio were similar in two groups. There was no significant difference regarding with age, gender and family history of FS between two groups. We found significant difference statistically with respect to gestational age, consanguinity, family history of epilepsy and birth weight between two groups. The mean levels of Hb, Htc, MCV were lower and Plt and RDW levels were higher in children with CFS than SFS group, the differences were statistically significant (p: 0.001). A higher proportion of children with CFS (16.2%) had iron deficiency anemia compared to SFS group (12.1%). Mean platelet volume (MPV) of CFS (7.99±0.96fL) were significantly lower than that of SFS group (8.77±0.75) (p<0.001). CONCLUSIONS The results of this study suggests that iron deficiency anemia is more frequently seen among the patients with CFS than the patients with SFS. The lower levels of MPV as an inflammatory marker, supports the idea that CFS is a brain inflammatory disease and the consequence of this inflammatory mechanism is the development of the epilepsy. Further studies are necessary to highlight the relationship between iron metabolism, inflammation and seizures.

Reversible pulmonary arterial hypertension in cobalamin-dependent cobalamin C disease due to a novel mutation in the MMACHC gene

Methylmalonic aciduria and homocystinuria, cobalamin C (CblC) disease (OMIM 277400), is the most frequent inborn error of vitamin B12 (cobalamin, Cbl) metabolism and is caused by an inability of the cell to convert Cbl to its active forms (MeCbl and AdoCbl). More than 75 mutations have been identified in the MMACHC gene which is responsible for CblC disease. We present a case with CblC disease and pulmonary arterial hypertension (PAH) as the main symptom. The patient improved dramatically with parenteral hydroxocobalamin treatment. Most cases of CblC disease have a multisystemic disease with failure to thrive, developmental delay, hypotonia, visual impairment, and hematologic manifestations. This patient had isolated pulmonary hypertension and hyperhomocysteinemia which is thought to be an important factor in the pathogenesis of PAH. Genetic analysis identified a novel homozygous mutation (c.484G > T; p.Gly162Trp) in the MMACHC gene. Conclusion: CblC disease should be considered in the differential diagnosis of pulmonary hypertension.

A Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of N-Terminal β-Barrel in Microsomal Triglyceride Transfer Protein Function

Background—The use of microsomal triglyceride transfer protein (MTP) inhibitors is limited to severe hyperlipidemias because of associated hepatosteatosis and gastrointestinal adverse effects. Comprehensive knowledge about the structure–function of MTP might help design new molecules that avoid steatosis. Characterization of mutations in MTP causing abetalipoproteinemia has revealed that the central &agr;-helical and C-terminal &bgr;-sheet domains are important for protein disulfide isomerase binding and lipid transfer activity. Our aim was to identify and characterize mutations in the N-terminal domain to understand its function. Methods and Results—We identified a novel missense mutation (D169V) in a 4-month-old Turkish male child with severe signs of abetalipoproteinemia. To study the effect of this mutation on MTP function, we created mutants via site-directed mutagenesis. Although D169V was expressed in the endoplasmic reticulum and interacted with apolipoprotein B (apoB) 17, it was unable to bind protein disulfide isomerase, transfer lipids, and support apoB secretion. Computational modeling suggested that D169 could form an internal salt bridge with K187 and K189. Mutagenesis of these lysines to leucines abolished protein disulfide isomerase heterodimerization, lipid transfer, and apoB secretion, without affecting apoB17 binding. Furthermore, mutants with preserved charges (D169E, K187R, and K189R) rescued these activities. Conclusions—D169V is detrimental because it disrupts an internal salt bridge leading to loss of protein disulfide isomerase binding and lipid transfer activities; however, it does not affect apoB binding. Thus, the N-terminal domain of MTP is also important for its lipid transfer activity.

3-HMG Coenzyme A Lyase Deficiency: Macrocephaly and Left Ventricular Noncompaction with a Novel Mutation.

Abstract3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency, an inborn error of ketone body synthesis and leucine degradation, is a rare autosomal recessive disease. There are a few reports demonstrating clinical and neuroradiologic findings of this condition. The authors report case of an 8-mo-old infant with HMG-CoA lyase deficiency, who presented with macrocephaly, left ventricular noncompaction, recurrent pulmonary infections, nonketotic hypoglycemia, seizure and metabolic acidosis. There was no significant difference in brain magnetic resonance imaging after leucine-restricted diet and carnitine therapy and neurologic deterioration was not observed. Left ventricular noncompaction is an interesting finding for HMG-CoA lyase deficiency which has not been reported in the literature. The genetic analysis revealed a novel homozygote deletion in exon 3 and 4 in HMGCL gene. HMG-CoA lyase deficiency should be thought in the patients with hypoketotic hypoglycemia, hyperammonemia, elevated liver function tests, noncompaction left ventricle and characteristic white matter changes and in the differential diagnosis of macrocephaly.

Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N-Terminal β-Barrel in Microsomal Triglyceride Transfer Protein Function.

Background—The use of microsomal triglyceride transfer protein (MTP) inhibitors is limited to severe hyperlipidemias because of associated hepatosteatosis and gastrointestinal adverse effects. Comprehensive knowledge about the structure–function of MTP might help design new molecules that avoid steatosis. Characterization of mutations in MTP causing abetalipoproteinemia has revealed that the central &agr;-helical and C-terminal &bgr;-sheet domains are important for protein disulfide isomerase binding and lipid transfer activity. Our aim was to identify and characterize mutations in the N-terminal domain to understand its function. Methods and Results—We identified a novel missense mutation (D169V) in a 4-month-old Turkish male child with severe signs of abetalipoproteinemia. To study the effect of this mutation on MTP function, we created mutants via site-directed mutagenesis. Although D169V was expressed in the endoplasmic reticulum and interacted with apolipoprotein B (apoB) 17, it was unable to bind protein disulfide isomerase, transfer lipids, and support apoB secretion. Computational modeling suggested that D169 could form an internal salt bridge with K187 and K189. Mutagenesis of these lysines to leucines abolished protein disulfide isomerase heterodimerization, lipid transfer, and apoB secretion, without affecting apoB17 binding. Furthermore, mutants with preserved charges (D169E, K187R, and K189R) rescued these activities. Conclusions—D169V is detrimental because it disrupts an internal salt bridge leading to loss of protein disulfide isomerase binding and lipid transfer activities; however, it does not affect apoB binding. Thus, the N-terminal domain of MTP is also important for its lipid transfer activity.

Children Pilomatricoma (Calcifying epithelioma): A case of AtypicalPlacement

Pilomatricoma is benign skin tumor originates from outer sheath of hair follicle cells and is usually locates on head, neck and upper extremities. 40% of pilomatricomas are diagnosed in the first decade of life. It is most commonly seen between the ages of 8-13 in children. These nodular tumors are rarely multiple and familial. Pediatricians are not so familiar to these tumors, so true initial diagnosisis is not usually feasible. The definitive diagnosis is made by histopathological examination of tissue obtained by excisional biopsy. Although its rare, because of tumors metastasis potential and recurrence potentiality in cases that accurate excision could not be obtained, wide surgical excision should be performed. The incidence of recurrence is very low. In this report; 10 months old male patient with pilomatricoma, diagnosed by pathology procedures, is presented who was examined detailly many times due to huge puffy mass in the head kept growing from 4 months of age.

Microsomal triglyceride transfer protein gene mutations in Turkish children: A novel mutation and clinical follow up

Abetalipoproteinemia (ABL; OMIM 200100) is a rare autosomal recessive disease that affects the absorption of dietary fats and fat soluble vitamins. Here, we describe the clinical and genetic characteristics of three patients with ABL. Two patients (patients 1 and 2) who were carriers of the c.398-399delAA mutation (previously known mutation) had developmental delay and hepatic steatosis developed at the age of five in patient 1. Patient 3 was the carrier of a novel mutation (g.10886-10902delAAGgtaagtttgtgttg in intron 3 and c.506A>T exon 5) in microsomal triglyceride transfer protein (MTP) gene and had hepatic steatosis.

A rare cause of protein losing enteropathy: collagenous sprue.

Collagenous sprue is a clinicopathological entity with an unknown etiology. Its clinical features include progressive malabsorption, diarrhea, weight loss, unresponsiveness to treatment, and high mortality rates. The age interval of collagenous sprue is quite broad and ranges between 2 and 85 years. As far as to our knowledge, the presented case is the first reported case in infancy.