Neonatal screening for biotidinidase deficiency: results of a 1-year pilot study in four cities in central Anatolia.

BACKGROUND: Biotin, a water-soluble vitamin, is used as a co-factor by enzymes involved in carboxylation reactions. It functions as the carboxyl carrier for biotin-dependent carboxylases. These enzymes catalyze gluconeogenesis, fatty acid metabolism and amino acid catabolism, thus biotin plays an essential role in maintaining metabolic homeostasis. Biotinidase deficiency is an inherited metabolic disorder characterized by neurological and cutaneous symptoms, treated by oral administration of the vitamin biotin. In central Anatolia marriages between relatives are very common (26%). INFANTS AND METHODS: We screened 34,378 infants born in four cities in central Anatolia during the one-year period beginning February 2006 for deficiency of the enzyme biotinidase. A simple calorimetric screening procedure was used to detect the presence or absence of biotinidase activity on the same blood-soaked filter paper cards used for screening for phenylketonuria. Positive samples were confirmed with a quantitative method. RESULTS: One newborn infant with partial biotinidase deficiency (10-30% of mean normal serum activity) was identified during the 12-month pilot study. The estimated incidence of partial biotinidase deficiency in central Anatolia is approximately 1:34,378; this ratio was the same in findings from Istanbul (1:33,307). CONCLUSIONS: Like children with profound biotinidase deficiency, children with partial biotinidase deficiency are symptom-free at birth. However, the subsequent occurrence of symptoms of profound biotinidase deficiency in our patient with partial deficiency suggests that biotin therapy for this condition may be warranted. It is known that in Turkey marriages between relatives are common. If the neonatal screening program is widened the real ratio can be determined, where marriages between relatives are very high in central Anatolia.

Enzyme replacement therapy in an infant with Pompe's disease with severe cardiomyopathy.

Pompe's disease is a glycogen storage disease (type II) characterized by inherited autosomal recessive transmission. A 4 month-old girl presented with rapid disease progression, exhibiting severe hypotonia, and hypertrophic cardiomyopathy, progressing to respiratory failure by the age of 9 months. Despite its low incidence, infantile Pompe's disease is lethal. The availability of an effective treatment has created an urgent need to improve knowledge and early diagnosis of this disease. The clinical response is variable from patient to patient with a better effect in patients enrolled earlier. The only clinically available therapy for Pompe's disease is enzyme replacement therapy (ERT). Gene therapy is still not available for Pompe's disease due to lack of suitable vectors for long-term and tissue-specific expression. Recombinant human alpha-glucosidase remains a hope for patients.

SLC11A1 (NRAMP1) but not SLC11A2 (NRAMP2) polymorphisms are associated with susceptibility to tuberculosis in a high-incidence community in South Africa.

SETTING: Stellenbosch University Faculty of Health Sciences, and metropolitan Cape Town, Western Cape, South Africa. OBJECTIVE: To investigate whether the reported association between SLC11A1 (also NRAMP1) polymorphisms and susceptibility to tuberculosis (TB) can be confirmed in a different population, and whether polymorphisms in SLC11A2 (also NRAMP2, DCT1, DMT1) are associated with TB. DESIGN: A case-control study design was used to compare the frequencies of five polymorphisms in SLC11A1 and three in SLC11A2 between a group of bacteriologically confirmed TB patients and healthy community controls. RESULTS: The 5' (GT)9 allele in the promoter of SLC1A1 was found at significantly higher frequencies among 265 controls than in 224 pulmonary TB (PTB) patients (P = 0.002; OR 0.6; 95% CI 0.43-0.83). Homozygotes for the TGTG deletion (1729+55del4) in the 3'UTR of SLC11A1 were over-represented among PTB patients (P = 0.013; OR 5.19; 95% CI 1.42-18.94). Stepwise logistic regression analysis indicated that the 5' and 3' polymorphisms contribute separate main effects. Tuberculous meningitis patients (n = 22) showed the same allele and genotype frequency as PTB patients. No SLC11A2 polymorphisms tested were associated with TB. CONCLUSION: The 5' (GT)n allele driving the highest rate of transcription of SLC11A1 appears to be associated with protection against TB in the majority of the populations studied.

Asymptomatic hypercalciuria: prevalence and metabolic characteristics.

Hypercalciuria is of continuing interest as a risk factor for kidney stones in children. We screened 592 healthy Turkish children (308 boys, 284 girls, aged 3 month-16 years) for hypercalciuria by measurement of urinary calcium/creatinine (UCa/Cr) ratio in the second-morning urine samples. Hypercalciuria was noted in 17 children (2.9%), 9 of them were boy and 8 of them were girl. Oral calcium-loading test could only be done in 7 children who were diagnosed as having hypercalciuria, and it revealed absorptive hypercalciuria in 2 cases and renal hypercalciuria in no cases. The frequency of a family history of urolithiasis in asymptomatic hypercalciuric children was 50%. Median UCa/Cr ratios and urinary magnesium/creatinine (UMg/Cr) ratios were 0.11 and 0.10 and the 97th percentiles were 0.32 and 0.23 respectively. The UCa/Cr ratio in second-morning urine samples was correlated with the UMg/Cr ratio (r = 0.44) and was independent of age and sex.

Serum free carnitine and total triglycerid levels in children with iron deficiency anemia.

Iron deficiency anemia and hyperlipidemia are common public health problems in Turkey. The connection between iron and lipid metabolisms has not been clarified yet. The aim of the study was to determine the effect of iron deficiency on carnitine and lipid metabolism. Study group was consisted of 70 children (mean age 14.7 +/- 1.3 months) suffering from iron deficiency anemia and 20 healthy children (mean age 13.7 +/- 1.2 months) attended to outpatient clinics of Cumhuriyet University, Sivas were enrolled the study as the control group. Assessments of serum free carnitine concentrations, total triglyceride, total cholesterol and VLDL levels were made in both groups. The mean serum free carnitine concentration was significantly lower than the control group (18.9 +/- 0.43 nmol/ml and 45.9 +/- 1.47 nmol/ml respectively, t = 17.5 p < 0.01). Results of our study also indicated higher serum total triglyceride, total cholesterol and VLDL levels in iron deficient patients than the healthy controls. Regression analyses indicated a negative correlation between serum free carnitine and total triglyceride levels in iron deficient patients. This study confirms that iron deficiency anemia may be linked to the endogenous carnitine synthesis in pediatric age group, and thus hyperlipidemia appears to be a risk factor for premature cardiovascular diseases.

Serum-free carnitine levels in children with heart failure.

The serum-free carnitine (SFC) levels of 91 children with heart failure (HF) and of a control group consisting of 30 healthy children were measured. Twenty-four of 91 children with HF were administered oral L-carnitine. The mean SFC level of children with HF (20.16 +/- 0.30 nmol/l) was significantly lower than that of the control group (38.98 +/- 0.79 nmol/ml) (p < 0.01). Mean SFC levels of 24 patients, after L-carnitine administration, increased significantly (p < 0.01). Patients administered L-carnitine displayed a marked difference in time taken for clinical improvement compared with those not given oral L-carnitine.

Effect of antiepileptic drugs on bone mineral density in children between ages 6 and 12 years.

We assessed the effects of sodium valproate and carbamazepine monotherapy on bone mineral density (BMD) in children. BMD at the lumbar vertebrae (L1-L4) and radius-ulna was measured by the dual-energy x-ray absorptiometry (DEXA) method in 19 children (9 girls, 10 boys) with uncomplicated epilepsy and in 57 healthy children (28 girls, 29 boys), between the ages of 6 and 12 years. The study patients had been receiving either sodium valproate (n = 13) or carbamazepine (n = 6) monotherapy for more than 6 months. There were no significant differences between the control and study patients in age, height, weight, physical activity, or of serum concentrations of calcium, phosphate, and transaminases (aspartate aminotransferase, alanine aminotransferase). However, the serum alkaline phosphatase concentration was greater in the patient group as compared with the control group. BMD values were lower in girl patients (L1-L4; 0.497 +/- 0.08 vs 0.566 +/- 0.07 g/cm2, p < 0.05), but not in boys (0.534 +/- 0.06 vs 0.530 +/- 0.08 g/cm2). While BMD reduction was 8% in valproate therapy (midregion of radius-ulna; 0.287 +/- 0.03 vs 0.312 +/- 0.04 g/cm2, p < 0.04), it was reduced only 4.5% in the carbamazepine-treated group (0.298 +/- 0.01 vs 0.312 +/- 0.04 g/cm2, statistically not significant), although the mean durations of monotherapy with valproate (1.8 +/- 0.7 years) and carbamazepine (1.7 +/- 0.8 years) were similar. Thus decreased bone mineralization was observed in children with epilepsy, treated with sodium valproate even though treatment was for a rather short time.

Serum free carnitine levels in children with recurrent pulmonary infections.

The serum free carnitine levels of 33 children with recurrent pulmonary infection and 30 healthy children were measured and found to be 26.12 +/- 0.98 nmol/mL and that of the control group 38.98 +/- 0.79 nmol/mL on the average. The mean free carnitine level was statistically determined to be significantly lower when compared with that of the control group (P < 0.01). The results indicate that oral L-carnitine therapy is recommended for pediatric patients with recurrent pulmonary infection.

Intravenous immunoglobulin for sepsis prevention in preterm infants.

The aim of this study was to investigate whether intravenous immunoglobulin (IVIG) can prevent sepsis in premature newborn infants. The study group consisted of 80 preterm newborn infants, who were divided into two groups: 40 preterm newborns received IVIG prophylactically (group A) and the control group (group B, n = 40) did not receive IVIG. IVIG was given at a dose of 500 mg/kg to infants. weighing greater than 1500 g, and 700 mg/kg to those weighing less than 1500 g at birth on days one, two and eight of life. By two, eight and 12 days of age, the treatment group had significantly greater IgG concentrations than the control group. Mortality was 7.5 percent (3/40) in group A and 27.5 percent (11/40) in group B (p < 0.01). Bacteremia was determined in three blood cultures in group A and eight in group B, particularly S.aureus and S.enteritis.

Blood glucose levels and hypoglycaemia in full term neonates during the first 48 hours of life.

Thirty-five full term infants (38-41 weeks' gestation) were included in the study. Infants of mothers with complications of pregnancy, such as toxaemia, anaemia, diabetes, or hypertension were not included. All infants were fed during the first 3 hours of life and this was continued every 4 hours. Maternal glucose estimation was carried out 15 or 30 min before or at the time of birth. Glucose levels were measured in all 35 newborns at the 1st, 2nd, and 3rd hour, and 14, 24, 36, and 48 hours before feeding. Serum glucose levels were measured using a Reflectron Glucose Analyser. The lowest blood glucose level was seen in the first 3 hours of life. In the first 3 hours of life there were 12 infants with glucose levels less than 30 mg/dl, but in only three of those did the hypoglycaemic level continue and require treatment (9 per cent). We concluded that hypoglycaemia which is seen in the first 3 hours can be physiological and early feeding appears to influence subsequent glucose values.

Immune globulin treatment in intractable epilepsy of childhood.

Six children suffering from epilepsy refractory to conventional anti-convulsive therapy were treated with high-dose intravenous immune globulin (IVIG) (200 mg/kg three times per week, repeated after three weeks). In four children clinical and EEG findings markedly improved, while a partial response was noted in the other cases. These results suggest that high-dose intravenous immune globulin may have a beneficial effect in the treatment of intractable epilepsy.

Childhood achalasia.

Achalasia is a motility disorder of the esophagus characterized by absence of normal peristalsis and failure of relaxation of the lower esophageal sphincter. Among the most common clinical findings are vomiting and weight loss. Roentgenographically, a narrowed gastroesophageal junction and dilated esophagus are observed. This condition is uncommon in children. Here a seven-year old female patient with achalasia is reported.

High-dose intravenous immune globulin in the management of severe Guillain-Barre syndrome.

Guillain-Barre Syndrome (GBS) is the most common cause of acute generalized paralysis. Although the cause and pathogenesis of GBS remain unknown, there is increasing evidence to suggest that this syndrome has an immunological basis. Two children suffering from GBS were treated with high-dose intravenous immune globulin (IVIG) (1 g/kg/day over two consecutive days). Both children showed marked clinical improvement within 48 hours of the onset of treatment. It is suggested, on the basis of recent case reports, that immunoglobulins may have an important role in the treatment of Guillain-Barre Syndrome.

The influence of maternal iron deficiency anaemia on the haemoglobin concentration of the infant.

Serum ferritin, iron, and haemoglobin (Hb) values of 27 pregnant women who did not receive oral iron therapy during pregnancy, and Hb of their normal full-term babies were determined. Maternal blood samples were obtained at 16 and 24 weeks of pregnancy and infants' blood samples were obtained at the first day and 3 months of life. Mothers were divided into two groups according to their serum ferritin values. By analysing the results we were not able to detect any correlation between maternal ferritin, Hb, and newborn gestational age, and Hb and birth weight. The same was found when the groups were compared by a maternal serum ferritin above and below 12 ng/ml.

Serum carnitine, beta-hydroxybutyrate and ammonia levels during valproic acid therapy.

This study was performed in order to determine the effects of valproic acid on serum free carnitine, beta-hydroxybutyrate and blood amamonia. Serum free carnitine, beta-hydroxybutyrate and blood ammonia levels were measured in 24 epileptic children and in 24 age and sex-matched controls. The mean serum free carnitine level was significantly lower in patients taking valproic acid (33.5 +/- 13.1 nmol/ml) than in control subjects (50.8 +/- 14.6 nmol/ml) (p < 0.001). The mean blood ammonia level was significantly higher in patients receiving valproic acid (93.9 +/- 20.5 micrograms/dl) than in controls (79.6 +/- 21.4 micrograms/dl) (p < 0.002). The mean serum beta-hydroxybutyrate level was significantly lower in patients taking valproic acid (2.26 +/- 2.24 mg/dl) than in controls (4.38 +/- 2.43 mg/dl) (p < 0.001).

Plasma free carnitine levels in children with malnutrition.

In this study, plasma free carnitine and albumin levels were measured in children with protein-energy malnutrition (PEM). A total of 71 children with malnutrition were studied. The control group consisted of 20 healthy children. The mean plasma carnitine level was 78.4 +/- 1.94 nmol/ml in the control group. Marasmus and kwashiorkor patients displayed lower plasma free carnitine values, which were found to be statistically significant when compared to those of the control (P < 0.001). However, the values were significantly lower in kwashiorkor patients than in marasmic cases (29.7 > 5.46). There was no correlation between serum albumin and free carnitine levels in cases with kwashiorkor.

Perforated duodenal ulcer: an unusual complication of meningitis.

An 11-month-old boy was admitted to the hospital with fever, vomiting and seizures and was diagnosed with purulent meningitis. Two days later, an acute, perforated, duodenal ulcer was detected in the patient. Surgery was performed, and the patient made an uncomplicated recovery. Peptic ulceration is underdiagnosed in children and this leads to delay in diagnosis and appropriate management. Peptic ulceration may occur during severe illness or viral infections, but perforation is rare.