Alev Hasanoglu

An overview of L‐2‐hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype–phenotype study

L‐2‐Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2‐hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT‐PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty‐five novel mutations as well as 35 reported mutations and 14 nondisease‐related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype–genotype relationship. Hum Mutat 30:1–11, 2010.

ARM ANTHROPOMETRY IN EVALUATION OF MALNUTRITION IN CHILDREN WITH CANCER

Malnutrition in children with cancer is reported to be relatively uncommon at the time of diagnosis. However, in most studies nutritional status measurement has relied almost exclusively on weight-related indices. This can be misleading, because in children with malignancy, tumor masses can reach more than 10% of total body weight. A controlled study was performed in 62 patients using arm anthropometry to provide a more accurate evaluation of the nutritional status of children with cancer at presentation. Height, weight, midupper arm circumference (MUAC), and triceps skinfold thickness (TSFT) were measured in all patients (40 boys, 22 girls) and controls (18 boys, 13 girls). Weight for height (WFH) of each patient was compared with the national standards. MUAC and TSFT were also interpreted according to the standards developed by A. Roberto Frisancho. The mean ages were 6.5 +/- 3.7 years (range 0.08-13) and 5.7 +/- 4.7 years (range 0.25-15) in patients and control group, respectively. Results showed that although the WFH values for patients were normal, MUAC and TSFT values were significantly less than control values (P < 0.001). Moreover, 27% of patients showed malnutrition (they had MUAC and TSFT below 5th percentile). Patients with intraabdominal solid tumors had significantly lower MUAC and TSFT values than those with extraabdominal solid tumors (P < 0.05). The data strongly indicate that malnutrition is common at the time of diagnosis in children with cancer, and arm anthropometry should replace the use of weight-related indices to identify malnutrition in children.

Serum leptin, oxidized low density lipoprotein and plasma asymmetric dimethylarginine levels and their relationship with dyslipidaemia in adolescent girls with polycystic ovary syndrome

Objective  The aim of this study was to investigate serum leptin, oxidized low density lipoprotein (ox‐LDL) and asymmetric dimethylarginine (ADMA) levels and their interaction with dyslipidaemia in adolescents with polycystic ovary syndrome (PCOS).

Bone mineral density in childhood obesity.

There are several metabolic and hormonal disturbances in childhood obesity. The purpose of this study was to determine the relationship between childhood obesity and bone mineral density (BMD). We studied BMD in 37 obese children and in 37 non-obese children. BMD was measured at L2-L4 level by using dual energy X-ray absorptiometry. BMD was significantly related to age, height and weight. The mean BMD in the obese children and control group was 0.655 +/- 0.175 and 0.626 +/- 0.159 g/cm2, respectively, without any statistically significant difference (p>0.05). There was no correlation between BMD values and osteocalcin or calcitonin levels. According to Tanners pubertal staging, the mean BMD of pubertal obese children was higher than that of prepubertal obese children. BMD of the pubertal obese children was significantly higher than that of the pubertal control group (p<0.05). Girls had higher mean BMD values than boys. In conclusion, our results show that BMD is not influenced by obesity in children but higher values in puberty were observed in obese children which may due to hormonal changes.

Frequency of vitamin D insufficiency in healthy children between 1 and 16 years of age in Turkey.

Background:  The aim of this study was to establish the frequencies of vitamin D deficiency and insufficiency among healthy children aged 1–16 years and also to determine the factors affecting the levels of vitamin D in Turkey.

Asymmetrical dimethylarginine level in atrial fibrillation

Objective — Atrial fibrillation (AF) is known to be related with increased risk of thromboembolic events. Asymmetrical dimethylarginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase (NOS), can cause endothelial dysfunction by decreasing nitric oxide (NO) and lead to increased risk of thrombosis. In the present study our aim was to compare plasma levels of ADMA in patients with acute onset (< 24 hours) and chronic AF (> 1 year) to determine the risk of thrombosis. Method — 17 patients with the first detected attack of AF within the first 24 hours of presentation (group I), 25 patients who had permanent chronic AF lasting at least 1 year or more (group II) and 18 healthy persons as the control group (group III) were included in the study. For each patient the plasma ADMA, L-arginine, symmetrical dimethylarginine (SDMA) concentrations were measured by high-performance liquid chromatography in venous blood samples collected before cardioversion. We compared the plasma ADMA, L-arginine and SDMA concentrations between the groups. Results — Plasma L-arginine (78.18 ± 28.29 vs. 73.14 ± 14.11 vs. 71.03 ± 21.31, P = 0.549) and plasma SDMA concentrations (0.38 ± 0.18 vs. 0.42 ± 0.21 vs. 0.32 ± 0.24, P = 0.224) were similar in all groups. There was a significant difference between plasma ADMA concentrations (0.76 ± 0.27 vs. 0.50 ± 0.26 vs. 0.36 ± 0.20, P < 0.001) among the groups.When we compared plasma ADMA levels between the subgroups, we also found a significant difference (P = 0.002 when comparing group I and group II, P < 0.001 when comparing of group I and group III, P = 0.042 when compareng of group II and group III). Conclusion — ADMA levels in patients with acute onset AF were significantly increased when compared with patients with chronic AF and the healthy control group indicating the presence of endothelial dysfunction and a prothrombotic state even in a very early phase of AF.

Endomysium antibodies in the diagnosis of celiac disease in short-statured children with no gastrointestinal symptoms.

Background : Endomysium antibodies (EmAb) are strongly associated with untreated celiac disease and are suggested to be diagnostic. The aim of the present study was to assess the value of anti‐EmAb for celiac disease screening in children with short stature.

Excitatory amino acids and taurine levels in cerebrospinal fluid of hypoxic ischemic encephalopathy in newborn

The recent studies indicating the transiently enhanced expression of excitatory amino acid receptors in hypoxia vulnerable brain regions and the elevated concentration of aspartate and glutamate in cerebrospinal fluid of asphyxiated newborns strongly suggest the role of excitatory amino acids in hypoxic ischemic brain damage in the developing human brain. In this study, we compared the concentrations of glutamate, aspartate, taurine and glycine in the cerebrospinal fluid of asphyxiated infants with values of a healthy control group. The concentrations of aspartate (5.82 +/- 3.36), glutamate (1.76 +/- 1.0) and taurine (9.32 +/- 9.1) were significantly elevated in cerebrospinal fluid of asphyxiated infants (P < 0.05). When compared to the control group, the high levels of aspartate was correlated with the degrees of hypoxic-ischemic encephalopathy (HIE) and the varying outcome. The high levels of aspartate and glutamate in the asphyxiated patients adds further evidence to the role of excitotoxicity in hypoxic ischemic encephalopathy. The mental and motor development of the patients in asphyxiated group was followed for 3 years.

Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in obese children.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) metabolism may be disturbed in obese children. We investigated serum GH, IGF-I, IGF-binding protein-3 (IGFBP-3) levels in 42 obese and 40 non-obese healthy children aged 6-14 years. GH stimulation tests with L-dopa and insulin were performed. Serum IGF-I levels were studied by immunoradiometric assay (IRMA) and IGFBP-3 levels by radioimmunoassay (RIA). IGF-I levels were significantly higher in the obese group (p < 0.05), but IGFBP-3 levels were not different from the control group. IGF-I and IGFBP-3 levels were significantly higher in the obese pubertal children than in the obese prepubertal ones (p < 0.05). A positive linear correlation was found between body mass index (BMI) and IGF-I levels (r = 0.51, p < 0.05). These results suggest that obesity may have a considerable effect on IGF-I.

N-carbamylglutamate treatment for acute neonatal hyperammonemia in isovaleric acidemia

Hyperammonemia occurs mainly in patients with branched-chain organic acidemias such as propionic, methylmalonic, and isovaleric acidemias. Its pathophysiological process is mainly via the competitive inhibition of N-acetylglutamate synthetase. Oral carglumic acid (N-carbamylglutamate) administration can correct hyperammonemia in neonates with propionic and methylmalonic acidemias, thus avoiding dialysis therapy. Isovaleric acidemia is an autosomal recessive disease of leucine metabolism due to deficiency of isovaleryl-CoA dehydrogenase. For the first time, we report a neonate with isovaleric acidemia, whose plasma ammonia concentration dropped dramatically after one oral load of carglumic acid. This experience suggests that carglumic acid could be considered for acute hyperammonemia resulting from isovaleric acidemia. However, trials with more patients are needed.