Biomedical subjects

Turgay Coşkun

Publications and source records attributed to Turgay Coşkun.

At least 19 recordsLinked to original sources

PubMed2007

A newborn with VLCAD deficiency. Clinical, biochemical, and histopathological findings.

Here we report a newborn with VLCAD deficiency with a severe neonatal onset type who presented with hypoglycemia, cardiomyopathy, mild hepatomegaly and slight hypoalbuminemia. The patient was also homozygous for a new missense mutation (R456H). Postmortem examination of the liver, heart and skeletal muscle revealed diffuse lipid accumulation in various amounts. Mild lobular and portal fibrosis as well as severe macrovesicular steatosis were also found in the liver. The fatal course of the patient may have resulted from diffuse lipid accumulation in the liver and myocardium, which probably began during the intrauterine life with slight hypoalbuminemia as a silent marker of this process.

Acyl-CoA Dehydrogenase, Long-Chain↗

PubMed2006

The efficacy of liver transplantation in malignant liver tumors associated with tyrosinemia: clinical and laboratory findings of five cases.

To evaluate clinical and laboratory findings of these patients and the efficacy of liver transplantation in children with hepatocellular carcinoma (HCC) and hepatoblastoma (HB) associated with tyrosinemia. Among 113 children with liver tumors diagnosed between 1972 and 2004 five patients had HCC or HB associated with tyrosinemia. The age at diagnosis of the HCC or HB ranged from 9.5 to 17 yr and male:female ratio was 1:4. During regular clinic visits for tyrosinemia, elevated alpha-fetoprotein (AFP) was detected in all patients. AFP levels ranged between 13.7 and 29 340 IU/mL. Radiological studies including ultrasound, computed tomography and magnetic resonance imaging showed heterogeneous parenchyma and nodules in the liver. The patients did not have any metastatic disease. The time from diagnosis of tyrosinemia to HCC or HB ranged from 9.25 to 15.25 yr. Histopathologically, four patients have been diagnosed as HCC and one patient had HB. All patients were given chemotherapy including cisplatin and adriamycin. In three patients, living-related liver transplantation was performed. They had no treatment after transplantation. All of them are disease free. One patient was treated with chemotherapy and right hepatectomy. She had no suitable donor for living-related liver transplantation. Three months after completing chemotherapy, she had recurrent tumor in the left lobe of the liver and she died with progressive disease. The last patient whose parents were not suitable as donors for living-related liver transplantation is waiting for a deceased donor graft. All patients had limited disease to liver due to close clinical and radiological follow up for tyrosinemia. In these patients liver transplantation is curative both for liver tumor and tyrosinemia.

Adolescent↗

PubMed2005

The molecular basis of familial hypercholesterolaemia in Turkish patients.

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipoprotein metabolism. In the majority of patients FH is caused by mutations in the gene for the low-density lipoprotein receptor (LDLR), and to date more than 700 mutations have been reported worldwide. In this study, 36 paediatric patients with a clinical diagnosis of FH (20 homozygous and 16 heterozygotes) were screened for mutations in the LDLR gene. Each exon, with intron-exon junctions, was screened by capillary fluorescent SSCP (F-SSCP) and heteroduplex analysis. Samples showing different band patterns were sequenced. Ten novel (including three frame shift small deletions or insertions) and seven known mutations were detected. A total of 37 out of the predicted 56 FH-causing alleles were identified (66.1%). No patients with the R3500Q mutation in the APOB gene were found. W556R was the most common mutation, explaining 21.4% of the predicted defective LDLR alleles. The novel sequence changes were deemed to be pathogenic if they altered a conserved amino acid (L143P, D147E, Q233H-C234G, C347G) or occurred in or close to a splice site (IVS 16+5) and were absent in DNA from 50 healthy Turkish subjects. These data confirm the genetic heterogeneity of FH in Turkey, and demonstrate the usefulness of F-SSCP for mutation detection.

Adolescent↗

PubMed2004

Is vitamin D hypothesis for schizophrenia valid? Independent segregation of psychosis in a family with vitamin-D-dependent rickets type IIA.

The vitamin D hypothesis of schizophrenia is a recent concept bringing together old observations on environmental risk factors and new findings on the neurodevelopmental effects of vitamin D. Candidate genes related to the vitamin D endocrine system have not yet been fully explored for this purpose. The coexistence of vitamin-D-dependent-rickets type II with alopecia (VDDR IIA) and different forms of psychosis in the same inbred family has provided us with an opportunity to investigate the presumed relationship between vitamin D deficiency and psychosis. Psychiatric examination and molecular genetic studies were performed in this family overloaded with psychotic disorders and VDDR IIA. Forty members were evaluated in order to describe their phenotypic features. The family was tested for a linkage to the chromosome 12q12-q14 region where the vitamin D receptor (VDR) gene is located. Psychosis was the common phenotype in the 18 psychiatrically affected members. Pedigree analysis did not show a cosegregation of psychosis and rickets. Lod scores were not significant to prove a linkage between psychosis and VDR locus. The authors concluded that (1) the neurodevelopmental consequences of vitamin D deficiency do not play a causative role in psychotic disorders, (2) these two syndromes are inherited independently, and (3) vitamin D deficiency does not act as a risk factor in subjects susceptible to psychosis.

Adolescent↗

PubMed2004

Serum selenium levels in acute gastroenteritis of possible viral origin.

Selenium, as an essential micronutrient, is required for the proper functioning of the immune system and its deficiency affects the occurrence, virulence, or disease progression of some viral infections. We conducted a study to determine the serum selenium levels of children with acute gastroenteritis of possible viral origin and the effect of the serum selenium levels on the severity and the morbidity of the disease. The study was performed prospectively on 109 children aged 2-24 months with diarrhea of less than 8 days' duration admitted to the Diarrheal Disease Training and Treatment Unit. Blood samples were taken for selenium measurement on admission and 7-10 days after the end of the disease. Forty-three healthy children formed the control group. The mean serum selenium level on admission (62.41 +/- 13.06 microg/dl) was significantly lower than the mean of the second samples 7-10 days after the end of the diarrhea (81.73 +/- 17.10 microg/dl). The mean of the control group was 74.36 +/- 10.75 microg/dl, which was lower than the mean of the second samples but higher than the first sample. The frequency of vomiting and purging on admission and at the control visit, duration of diarrhea on admission, total duration of diarrhea, dehydration, breastfeeding, sex of the patients, and severity score of the disease did not alter the serum selenium levels. No correlation was detected between serum selenium levels and the parameters above. Further studies about the changes in selenium status during infectious diseases and the effect of selenium status on related mortality and morbidity are required to determine if there is need for supplementation.

Acute Disease↗

PubMed2004

A boy with spastic paraparesis and dyspnea.

A 4 1/2-year-old boy with signs and symptoms of spastic paraparesis and dyspnea is presented. Biotinidase deficiency was considered and was confirmed by both urine organic acid analysis and biotinidase activity measurement. The child recovered gradually on biotin therapy. Because other systemic signs and symptoms of the disease might not be present initially or might develop later, biotinidase deficiency should be considered in the differential diagnosis of a child presenting with acute or subacute spastic paraparesis.

Biotin↗

PubMed2003

Relationship of leptin and insulin-like growth factor I to nutritional status in hemodialyzed children.

Malnutrition is prevalent in patients with end-stage renal disease (ESRD). Elevated serum leptin levels were thought to contribute to the anorexia and poor nutrition in renal failure. However, studies of the relationship between nutritional status and leptin concentration in chronic renal failure have yielded conflicting results. Plasma insulin-like growth factor I (IGF-I) level has been used as an indicator of nutritional status in patients with renal failure. The relationship between leptin and IGF-I is controversial. The present study was conducted with the aim of assessing the relationship between nutritional status, hyperleptinemia, and serum IGF-I. Seventeen ESRD patients (8 male, 9 female), aged 8-18 years (mean 15.3+/-3.3 years) and undergoing standard hemodialysis for 58.8+/-23.1 months were enrolled. Nine age-matched healthy children served as controls. In all patients, energy and protein intakes were 40-70 kcal/kg per day and 1-1.54 g/kg per day, respectively. Predialysis serum leptin and IGF-I levels were measured by radioimmunoassay. Body mass index was decreased in 13 (76%) patients. Triceps skinfold thickness (TST) was reduced (below the 5th percentile) in 7 (41%), whereas mid arm circumference and mid arm muscle circumference were reduced in 14 (82.5%) and 13 (76.5%), respectively. The median serum leptin level was significantly higher in patients than in controls [13.7 interquartile range (IQR) 30.50 pg/ml vs. 6.50 IQR 8.65 pg/ml, P=0.01]. The median serum IGF-I level was lower in the patients (205.1 ng/ml IQR 194.4 ng/l) than controls (418.0 ng/l IQR 310.5 ng/ml) ( P=0.01). IGF-I levels were more decreased in patients with severe malnutrition, defined according to TST (145.0 ng/ml IQR 125.5 ng/l) than patients without malnutrition (301.2 ng/l IQR 218.8 ng/ml) ( P=0.03) and healthy children ( P=0.002). Although statistically not significant, IGF-I levels tended to be decreased, while leptin levels were increased. The median plasma insulin concentration was 15 microU/ml (1.63-45.80) and did not correlate with leptin and IGF-I levels. In conclusion, the results of this study confirm the presence of high circulating plasma leptin levels, which may be one of the many factors involved in the pathogenesis of the malnutrition in children on hemodialysis.

Adolescent↗

PubMed2003

Transient nonketotic hyperglycinemia: two case reports and literature review.

Transient nonketotic hyperglycinemia is characterized by clinical and biochemical findings similar to those seen in classic nonketotic hyperglycinemia. Abnormalities in amino acids are partially or completely resolved in a period ranging from days to months. Almost all patients with the classic form of nonketotic hyperglycinemia survive with severe neurologic sequela, whereas most of the patients with the transient form exhibit normal development. Therefore, distinguishing the transient form of nonketotic hyperglycinemia from classic nonketotic hyperglycinemia is important to predict outcome of the patients. Transient nonketotic hyperglycinemia has been reported in only seven neonates. This article adds two cases to the transient nonketotic hyperglycinemia and reviews the relevant literature. Common clinical features were determined, and presence of miotic pupils was stressed.

Fatal Outcome↗

PubMed2003

The effects of aflatoxin B1 on the development of kwashiorkor in mice.

Seventy Swiss albino mice (6-week-old male) were selected for the investigation into aflatoxin B1's role in the cause of kwashiorkor. The mice were divided randomly into four groups. They were grouped within each group by being fed either low or normal protein level diets supplemented with very small amounts of aflatoxin B1 (0.5 microg/day). The control groups were fed aflatoxin B1-free diets containing either normal or low protein levels. All groups were monitored for 7 weeks. The increase in body weight was found to be low in groups I and II, given diets contaminated with aflatoxin B1. Although groups II and IV, which were given low dietary protein, showed remarkable decreases in serum total protein and albumin levels (group II: total protein 4.1 +/- 0.1 g/dL, albumin 2.6 +/- 0.8 g/dL and group IV: total protein 4.6 +/- 1.3 g/dL, albumin 2.8 +/- 0.82 g/dL) when compared with the groups fed a normal dietary protein level (group I: total protein 5.9 +/- 1.3g/dL, albumin 3.4 +/- 0.7g/dL and group III: total protein 5.4 +/- 1.6g/dL, albumin 3.5 +/- 1.2g/dL; P < 0.05). The statistical difference between these two groups was found not to be significant (P > 0.05). However, decreases in total protein and albumin levels were a little more prominent in group II. In addition, histopatological changes of the liver was remarkable in the group fed a low protein diet and aflatoxin B1 when compared with the group fed only a low protein diet and no aflatoxin B1. More significantly, however, was the increase in liver weight in both groups fed a low protein diet (groups II and IV). Our conclusion is that aflatoxin B1 could not have contributed to the development of kwashiorkor.

Aflatoxin B1↗

PubMedDate not supplied

Serum carnitine levels of pediatric cancer patients.

Secondary carnitine deficiency may occur in some diseases including malnutrition. The present study examined the serum carnitine levels of children with cancer and their relationship with nutritional status. Fifty-one (mean age: 104 +/- 23 months) patients with cancer were evaluated at diagnosis and 3 months after the initiation of the treatment. There were significant differences between the mean carnitine levels of patients before and during the treatment (p: .004). Although initial carnitine levels of patients were similar to those in control groups, there was a significant dif ference between the mean carnitine levels of patients and those of the control group at the third month (p: .02). The prevalence of malnutrition at the third month of the treatment (43%) was higher from the prevalence at diagnosis (33%) but this was not significant. No significant relationship was found between carnitine levels and nutritional status of patients either at diagnosis or during treatment. These results showed that inadequate intake of carnitine or its precursors could not be responsible for decrease in carnitine levels. Metabolic changes that result from therapy and/or from neoplastic process may be responsible for the decrease in carnitine levels. Detailed studies, including measurements of fractions of carnitine and urinary carnitine excretion according to individual drug, are necessary to determine real cause of this decrease.

Adolescent↗

PubMedDate not supplied

Refeeding problems in a severe anorexia nervosa case.

Anorexia Nervosa (AN) is an eating disorder of puberty or adolescence. It is characterized by self-induced weight loss; various psychological disturbances including distorted body image, fear of obesity, active pursuit of thinness and loss of recognition of a number of body enteroreceptive sensations; and secondary physiological abnormalities. The treatment of AN includes individual psychotherapy, family therapy, and nutritional rehabilitation. Hospital treatment is required when the patient's medical condition is in danger due to hypovolemia or hypotension. If cardiac arrhythmias occur without electrolyte disturbances or if oral therapy fails, nutrition should be repleted by the safest method available. This can be done by nasogastric tube or intravenous hyperalimentation. The management of AN is challenging, because the treatment process and anticipated outcome is in direct conflict with the sufferer's own wishes. A comprehensive treatment plan including both psychiatric and medical approaches is necessary. We report a severe AN case, who has refeeding problems after a three months' hospitalisation period. She was admitted to the child intensive care unit due to deterioration of her vital signs. We tried to solve her problems as a team, and believe that AN has a number of crucial problems thus requiring a multi-faceted treatment approach.

Adolescent↗

PubMedDate not supplied

Biochemical and molecular analysis of mucopolysaccharidoses in Turkey.

The mucopolysaccharidoses (MPSs) are a family of heritable disorders caused by deficiency of lysosomal enzymes needed to degrade glycosaminoglycans (GAGs). The undegraded or partially degraded GAGs are stored in lysosomes and/or excreted in urine. In our study, 118 patients seen over the past 20 years and suspected to have lysosomal storage disorders (LSDs) were subjected to clinical and biochemical analysis at Hacettepe University Children's Hospital. We analyzed urine and blood samples from 42 patients given a clinical MPS diagnosis. Using urine screening technique, we were able to show that 34 of the 42 patients had MPS condition. Further analysis of eight patients with normal urine MPS patterns revealed four patients as likely to have alpha-mannosidosis, fucosidosis, sialidosis, and aspartylglucosaminuria (one each). Four patients had normal oligosaccharide patterns. We were able to clearly identify 4 MPS I, 2 MPS II, 5 MPS IIIA, 8 MPS IIIB, 11 MPS IVA, 3 MPS VI, and 1 MPS IIIC patients. These results provided biochemical diagnosis for these 34 patients, and clearly show that Turkey has a higher incidence of MPS IVA, IIIB, and IIIA than of previously suspected MPS types. Molecular analysis of four MPS I patients revealed three polymorphisms which have been previously reported (A314, T388, and A461T). In MPS II patients, mutation analysis identified one previously detected (R172X) and one novel mutation (W109C).

Child↗

PubMedDate not supplied

Nutritional status of children with cancer and its effects on survival.

In the present study we aimed to determine the nutritional status of our patients and to assess its relationship with survival. The nutritional status of 47 patients with cancer was evaluated at diagnosis, three months after initiation of the treatment and at the end of therapy. Weight for height, height for age, and weight for age of children were expressed as percent of standard. Values for each nutritional index were converted into standard deviation (Z) scores. Three-year overall survival (OS) and event-free survival (EFS) rates of patients were determined according to their nutritional status. The overall prevalence of malnutrition at diagnosis was 29.8%. Three months later the malnutrition ratio reached 38.3% and then decreased again to 18.5% at the end of the therapy. Although the prevalence of malnutrition at the third month of treatment was significantly higher from the prevalence at diagnosis (p: 0.001) and at the end of the therapy (p: 0.009), the mean Z scores of the nutritional indexes before and during the treatment were not significantly different. The survival rates of malnourished patients were not different from those of well nourished patients. In conclusion, malnutrition is one of the main problems in children with cancer; hovewer, nutritional status has no effect on survival.

Adolescent↗

PubMedDate not supplied

Phenylketonuria and glycogen storage disease type III in sibs of one family.

Hyperphenylalaninemia result from a block in the conversion of phenylalanine into tyrosine due to a defect in either the enzyme phenylalanine hydroxylase (98% of subjects) or in the metabolism of the cofactor tetrahydrobiopterin. Phenylalanine hydroxylase deficiency is the most common form of inherited hyperphenylalaninemia disorders, with a prevalence between 1/4,000-1/40,000. Glycogen storage disease (GSD) type III is caused by debranching enzyme deficiency of glycogen degradation. The clinical features vary in relation to the localization of the enzyme defect. Two clinical entities exist: a combined hepatic myogenic form (GSD IIIa) and a purely hepatic form (GSD IIIb). The inheritance is autosomal recessive. We describe a Turkish family in which two girls were found to have phenylketonuria, while in two other sisters glycogen storage disease type III was diagnosed. The parents of these children are cousins and they have had 12 children.

Child↗

PubMedDate not supplied

Alpha-mannosidosis and mutational analysis in a Turkish patient.

We present a case of alpha-mannosidosis with its mutational analysis. She was referred to our hospital with the provisional diagnosis of mucolipidosis. She was the first child of second-degree relative parents. She had a coarse face with flat and wide nasal bridge, hepatosplenomegaly, umbilical hernia, lumbar gibbus, motor and mental retardation and deafness. On peripheral blood smear, lymphocytes revealed vacuoles and neutrophils contained some granules resembling Reilly bodies seen in mucopolysaccharidosis (MPS). Based on these findings, the diagnosis of alpha-mannosidosis was suspected. Her urine oligosaccharide chromatography showed an abnormal pattern with a heavy trisaccharide band. Enzyme studies on white cells confirmed a deficiency of alpha-mannosidase activity, which was 2.6 micromol/g/hr. Her DNA analysis showed a S453Y mutation.

Child, Preschool↗

PubMedDate not supplied

Effect of topiramate on enlargement of head in Canavan disease: a new option for treatment of megalencephaly.

Canavan disease (CD) is a rare autosomal recessive genetic disorder characterized by early onset progressive spongy degeneration of the brain involving the axon's myelin sheath. Patients with CD have leukoencephalopathy and megalencephaly; clinically they show a variable course ranging from slow neurodegenerative course to no neurological development or rapid regression. Current treatment is symptomatic including management of seizures and spasticity. Topiramate (TPM) is a novel antiepileptic drug for treatment of a broad spectrum of seizure types in adults and children. We used TPM in two of our patients diagnosed with CD at six months of age. At seven months and 15 months' follow-up, respectively, each patient showed a decrease in head growth velocity. We suggest that TPM can be used in patients with CD and possibly in other childhood neurodegenerative diseases with leukoencephalopathy and megalencephaly. Further studies are required to reveal the underlying mechanisms that lead to decreased head growth velocity, and to conclude whether this ameliorates the clinical course of CD.

Anticonvulsants↗

PubMedDate not supplied

L-2-hydroxyglutaric aciduria: a report of 29 patients.

L-2-hydroxyglutaric aciduria (L2HGA) is a chronic slowly progressive neurodegenerative disease characterized mainly by psychomotor developmental delay and cerebellar dysfunction. We report the clinical, biochemical, and neuroimaging features of 29 patients from 22 families. The mean age at the time of diagnosis was 13.4 years (2.5-32 years). The mean follow-up period of patients was four years (1.5-16 years). The main clinical findings were mental retardation and cerebellar involvement with ataxic gait and intentional tremor. Additional findings were mental retardation, macrocephaly and seizures. Diagnosis was confirmed by increased urinary excretion of L-2-hydroxyglutaric acid in all patients and highly specific magnetic resonance imaging (MRI) pattern showing subcortical leukoencephalopathy with bilateral high signal intensity in dentate nuclei and putamens. During the follow-up period, all patients had a static encephalopathy course. The underlying metabolic defect and the possible role of L-2-hydroxyglutaric acid are studied in a subgroup of these families and under evaluation for publication.

Adolescent↗

PubMedDate not supplied

Neurophysiologic features in glutaric aciduria type I.

Neurophysiologic abnormalities are frequently seen in organic acidemias, but knowledge of the specific changes in the different types of organic acidemias is lacking. We studied electroencephalogram (EEG), visual evoked potential (VEP) and brain-stem auditory evoked response (BAER) in seven children with glutaric aciduria type I (GA1) to assess the neurophysiologic features in this rare inborn error of metabolism. Age at the time of the diagnosis ranged between 3 months and 36 months. Age at the time of neurophysiologic evaluation ranged between 11 months and 36 months. At the time of neurophysiologic evaluation, severe global developmental delay was seen in four patients, dystonia in four patients, motor delay in two patients, and axial hypotonia in two patients; macrocephaly, spasticity, moderate mental retardation and borderline intelligence were each seen in one patient. One patient had autistic features characterized by lack of language and social skills, poor eye contact and stereotypical behavior. Three of seven patients showed abnormal EEG findings. Two patients showed asymmetry with intermittent occipital delta slowing in one hemisphere. This finding probably indicates underlying cerebral dysfunction, and is not a specific feature. However, it suggests that these patients may develop abnormal EEG features during the course of the disease, and thus a baseline EEG may be useful for comparison over time. One patient showed high amplitude bursts of beta in the occipital regions with left predominance while on clonazepam and baclofen. We believe this finding was due to medication effect, and that what we observed was an exaggarated response to benzodiazepine. The clinical significance of this finding is unclear. VEP and BAER were available in four patients, and we found abnormalities in three of them. Neurophysiologic evaluation may be helpful in patients with GA1 as in other types of organic acidemias to help detect subtle changes that are not reflected by neurological examination or neuroimaging studies, and it may guide future treatment plans. Detailed neurophysiologic analysis in a large series of GA1 may yield further information regarding the extent of cerebral dysfunction.

Amino Acid Metabolism, Inborn Errors↗