Halil Ibrahim Aydin

Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters

SummaryObjectives Isolated methylmalonic acidurias (MMAurias) are caused by deficiency of methylmalonyl-CoA mutase or by defects in the synthesis of its cofactor 5′-deoxyadenosylcobalamin. The aim of this study was to evaluate which parameters best predicted the long-term outcome. Methods Standardized questionnaires were sent to 20 European metabolic centres asking for age at diagnosis, birth decade, diagnostic work-up, cobalamin responsiveness, enzymatic subgroup (mut0, mut−, cblA, cblB) and different aspects of long-term outcome. Results 273 patients were included. Neonatal onset of the disease was associated with increased mortality rate, high frequency of developmental delay, and severe handicap. Cobalamin non-responsive patients with neonatal onset born in the 1970s and 1980s had a particularly poor outcome. A more favourable outcome was found in patients with late onset of symptoms, especially when cobalamin responsive or classified as mut−. Prevention of neonatal crises in pre-symptomatically diagnosed newborns was identified as a protective factor concerning handicap. Chronic renal failure manifested earlier in mut0 patients than in other enzymatic subgroups. Conclusion Outcome in MMAurias is best predicted by the enzymatic subgroup, cobalamin responsiveness, age at onset and birth decade. The prognosis is still unfavourable in patients with neonatal metabolic crises and non-responsiveness to cobalamin, in particular mut0 patients.

Analysis of heart rate variability in children with primary nocturnal enuresis

Although nocturnal enuresis is probably the most common developmental disorder in children, the pathogenesis and management remain unclear. Autonomic dysfunction is one of the proposed mechanisms for nocturnal enuresis in children. The objective of current study was to evaluate autonomic nervous system functions in enuretic children. Twenty-four-hour ambulatory electrocardiographic recordings were obtained, and the time domain variables of HRV were calculated. The results of the present study suggest that sympathetic nervous system hyperactivity is present in enuretic children. This may explain why some enuretic children do not respond to anticholinergic medications. If these conflicting results are confirmed by large-scale clinical studies, Holter ECG examinations may be used for rational approaches in treatment of nocturnal enuresis.

Bone age in children with nocturnal enuresis.

It is widely believed that nocturnal enuresis is caused by a hereditary delay in maturation of the various organ systems. In this study, growth and bone age were investigated in enuretic children. There was a significant bone age lag in the enuretic group compared to the control subjects of similar age (8.15 ± 1.56 years vs 9.45 ± 2.17 years, p < 0.05). It has been suggested that skeletal maturation also are retarded in nocturnal enuresis; and, it may be caused by the delayed maturation in regulatory functions of the central nervous system

Two novel deletions in hypotonia–cystinuria syndrome

Hypotonia-cystinuria syndrome (HCS) is an autosomal recessive disorder caused by combined deletions of SLC3A1 and PREPL. Clinical features include cystinuria, neonatal hypotonia with spontaneous improvement, poor feeding in neonates, hyperphagia in childhood, growth hormone deficiency, and variable cognitive problems. Only 14 families with 6 different deletions have been reported. Patients are often initially misdiagnosed, while correct diagnosis enables therapeutic interventions. We report two novel deletions, further characterizing the clinical and molecular genetics spectrum of HCS.

Adipokine, adropin and endothelin-1 levels in intrauterine growth restricted neonates and their mothers

Abstract Intrauterine growth retardation/restriction (IUGR) is associated with fetal malnutrition. It has consequences for later life including increased incidence of obesity, diabetes mellitus, cardiovascular disease (CVD), and metabolic syndrome. Adipokines (adiponectin and leptin), adropin, and endothelin-1 are associated with obesity and metabolic syndrome regulation. Intrauterine changes in these mediators could affect programming of later adult obesity and metabolic syndrome. Our objectives were to compare the levels of these mediators in both cord and maternal blood between IUGR pregnancies and control, healthy pregnancies, and to study the correlation of adipokines with adropin and endothelin-1 in maternal and cord blood in IUGR pregnancies as well as in healthy control pregnancies. Maternal and cord blood samples were taken from 16 women with IUGR pregnancies and 16 women with healthy pregnancies. Serum levels of leptin, adiponectin, adropin, and endothelin-1 were measured by ELISA. Maternal blood adropin levels were significantly lower in the IUGR group than in the control group; the other mediators did not differ significantly. There was a positive correlation between maternal blood adropin and endothelin levels. (r=0.731, P=0.001) in the control but not the IUGR group. Cord blood adropin and adiponectin levels were significantly lower in the IUGR group compared with the control group, while leptin or endothelin-1 did not differ significantly. There was a negative correlation between adropin and leptin (r=–0.704, P=0.001) in the IUGR but not the control group cord blood. There were also positive correlations between endothelin and adropin for both groups (r=0.594, P=0.006; r=0.560, P=0.010, respectively); to the best of our knowledge, this is the first report of such a correlation. Differences in fetal expression of adropin and adiponectin in IUGR could influence programming of obesity, metabolic syndrome, diabetes, and CVD in later life.

Hand and heart, hand in hand: is radiological hand osteoarthritis associated with atherosclerosis?

Increasing evidence suggests that atherosclerosis contributes to the initiation or progression of osteoarthritis (OA). It has been suggested that atherosclerosis may cause vascular insufficiency which may lead to or progress OA. In this study, the association between the severity of radiologic hand OA and atherosclerosis was analyzed in women.

Analysis of DNA Damage Using the Comet Assay in Infants Fed Cow’s Milk

It has been hypothesized that non-human milk feeding may increase the risk for cancer or for a specific cancer or group of cancers as well as the risk for diseases such as type-1 diabetes mellitus and Crohn’s disease. Regarding DNA damage leading to cancer development in the absence of human milk protection, a comparison between infants fed human milk and cow’s milk has been performed. Each group consisted of 35 infants, whose ages ranged from 9 to 12 months. The level of DNA damage in the peripheral blood lymphocytes of infants has been studied by the comet assay. A significant increase has been found in the number of limited DNA-damaged (p < 0.001) and extensive DNA-damaged (p < 0.001) cells of infants fed cow’s milk. To our knowledge, this is the first study using the comet assay on infants not breast-fed. Supporting our previous SCE study, these results suggest that there is some level of DNA damage in the lymphocytes of infants not breast-fed and this may lead to malignancy in childhood or later in life.

Preliminary study on DNA damage in non breast‐fed infants

Background : There are many advantages of human milk for infants, including protection against cancer development and the advantages have been emphasized in several studies. In this study, infants fed by human milk has been compared with those fed by cow’s milk concerning DNA damage.

Sister-Chromatid Exchange Analysis on Long-Term Benzathine Penicillin For Secondary Prophylaxis of Rheumatic Fever

A single intra-muscular injection of 1.2 millions units of benzathine penicillin every 4 weeks is the most widely used method for the antibiotic prophylaxis of rheumatic fever. The aim of this study is to evaluate the effect of long-term benzathine penicillin on DNA in patients with rheumatic fever. Thirty children with confirmed rheumatic fever who were on the benzathine penicillin prophylaxis were enrolled in the study, and 30 similar normal children served as a control group. To detect any DNA damage, SCE analysis were performed in circulating lymphocytes of the subjects. A statistically significant increased frequency of SCE was observed in children on the benzathine penicillin prophylaxis (no = 30, mean SCEs / cell ± SD 7.54 ± 1.81 ) as compared to a control group (no = 30, mean SCEs / cell ± SD 5.82 ± 1.40). It has been suggested that the difference in the SCE frequencies was induced by the administration of the benzathine penicillin for a long time, and further investigations are needed to confirm this toxic effect.

Serum dipeptidyl peptidase-IV: A better screening test for early detection of mucopolysaccharidosis?

We aimed to investigate the diagnostic utility of serum DPP-IV enzyme activity, urinary GAG/Cre ratio, chitotriosidase activity, total adenosine deaminase (ADA) and ADA-1 isoenzyme activity in the diagnosis of MPS. 31 MPS patients which were previously diagnosed by clinical and enzymatic analysis and 31 healthy controls matched with age and gender were included in this study. Serum DPP-IV enzyme activity, urinary GAG/Cre ratio, total ADA and ADA-1 isoenzyme activity were significantly higher in patients than in controls (p<0.001, p<0.001, p=0.038 and p=0.006, respectively). There were significant correlations between serum DPP-IV enzyme activity and urinary GAG/Cre ratios, ADA-1 activity, ADA-1/total ADA (r=0.498, p<0.001; r=0.348, p=0.006; r=0.270, p=0.034, respectively). Area under ROC curve for DPP-IV enzyme activity was 0.988, p<0.001 and for urinary GAG/Cre ratio was 0.986, p<0.001. DPP-IV enzyme activity and urinary GAG/Cre ratio were the most significant parameters according to the univariate logistic regression analysis (p=0.001 and p<0.001, respectively). The measurement of serum DPP-IV enzyme activity can be used complementary to the urinary GAG/Cre ratio for first-line MPS screening, since it is more less prone to age and hydration related interferences.