Folate deficiency in patients with classical galactosemia: A novel finding that needs to be considered for dietary treatments.

Çelik M, Özgün N, Akdeniz O, Fidan M, Tüzün H, Ipek MS, Emecan M, Eminoglu FT. Folate deficiency in patients with classical galactosemia: A novel finding that needs to be considered for dietary treatments. Turk J Pediatr 2018; 60: 540-546. The objectives of the study were to assess folate deficiency in patients with classic galactosemia, and to determine whether folic acid supplementation has an effect on galactose-1-phosphate uridyltransferase enzyme activity. Sixty-one newborn infants diagnosed with classic galactosemia between 2010 and 2017 were retrospectively evaluated. Within this group, 48 patients with Q188R homozygous mutation alone were enrolled into the study. Serum folate concentration was studied using chemiluminescence; and in folate deficient patients, galactose-1-phosphate uridyltransferase measurements before and after folic acid supplementation (100 mg/day folic acid for 30 days) were performed using an enzymatic calorimetric measurement technique based on kinetics. The serum folate level was low ( < 4 ng/ml) in 12 patients (25%). The galactose-1-phosphate uridyltransferase enzyme activity after folic acid supplementation was significantly higher than the values before folic acid supplementation (1.00±0.19 U/g Hb vs. 0.74±0.23 U/g Hb, p < 0.05); but was still less than the normal levels. Folate deficiency, most likely due to poor dietary intake, may develop in pediatric patients with classical galactosemia, and folic acid should be supplemented. Folic acid supplementation appears to have a low, but statistically significant, effect on galactose-1-phosphate uridyltransferase enzyme activity, but comprehensive research is needed to clarify whether there is any clinical significance.

Sirolimus-Induced Hepatitis in Two Patients with Hyperinsulinemic Hypoglycemia

Sirolimus has been reported to be effective in the treatment of the diffuse form of congenital hyperinsulinism (CHI), unresponsive to diazoxide and octreotide, without causing severe side effects. Two newborns with CHI due to homozygous ABCC8 gene mutations were started on sirolimus aged 21 and 17 days, due to lack of response to medical treatment. A good response to sirolimus was observed. At follow-up after ten and two months of treatment, liver enzymes were found to be increased [serum sirolimus level 1.4 ng/mL (normal range: 5-15), aspartate aminotransferase (AST): 298U/L, alanine aminotransferase (ALT): 302U/L and serum sirolimus level: 9.9 ng/mL, AST: 261U/L, ALT: 275U/L, respectively]. In Case 1, discontinuation of the drug resulted in normalization of liver enzymes within three days. Two days after normalization, sirolimus was restarted at a lower dose, which resulted in a repeated increase in transferases. In Case 2, a reduction of sirolimus dose caused normalization of liver enzymes within ten days. When the dose was increased, enzymes increased within three days. Sirolimus was discontinued in both cases. The rapid normalization of liver enzyme levels after sirolimus withdrawal or dose reduction; elevation of transaminases after restart or dose increase and rapid normalization after sirolimus withdrawal were findings strongly suggestive of sirolimus-induced hepatitis. To the best of our knowledge, this is the first report of sirolimus-induced hepatitis in CHI. Sirolimus is a promising drug for CHI patients who are unresponsive to medical treatment, but physicians should be vigilant for adverse effects on liver function.

Problems of the neonates with congenital heart disease requiring early interventions: a regional report.

AIM: In this study, it was aimed to determine the problems of the neonates who were diagnosed with congenital heart disease requiring early intervention in our hospital. MATERIAL AND METHODS: The files of the newborn babies with congenital heart disease requiring early intervention who were admitted to the neonatal intensive care unit of our hospital between January 2011 and January 2013 were evaluated retrospectively. In all cases, echocardiography and ''Score for Neonatal Acute Physiology-II" (SNAP-II) scoring were performed within the first day of admission. The data were interpreted using Number Cruncher Statistical System 2007 software. The statistical significance was set at p<0.05. RESULTS: A total of 83 babies were included in the study. Forty six of the patients were male (55%), and 37 (45%) were female. Sixty eight percent of the patients were referred from the neighboring provinces and 32% were transferred from the centers within the city. The age range was between 0 and 28 (5.6±6.4 day) days. The SNAP-II scores upon admission ranged between 0 and 90 (mean: 20±20.3). None of the patients was diagnosed prenatally. The most common diagnoses included transposition of the great arteries (33.7%) and pulmonary atresia (19.3%). Nineteen (22%) patients were lost in the neonatal intensive care unit. There was a significant relationship between the mortality and the SNAP-II scores (p=0.0001) and use of vasopressors (p=0.004). The diagnosis, gender, use of alprostadil and age were not related to mortality. Three patients were discharged following planning of elective surgery and 60 patients were referred to a tertiary center by air ambulance. CONCLUSIONS: The results of our study indicated that prenatal diagnosis could not be made in neonates with congenital heart disease requiring intervention in our region. The mortality rates of these patients were related to the severity of the clinical status at presentation rather than to the age, gender and type of congenital heart disease. The mortality was much higher in the patients who developed circulatory failure. Most of the patients who survived were sent by air ambulance to the centers where the intervention was to be performed.

Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations.

BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. DESIGN AND METHODS: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. RESULTS: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. CONCLUSIONS: Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.

Mutations in BTD gene causing biotinidase deficiency: a regional report.

Biotinidase deficiency is an autosomal recessive inborn error of biotin metabolism. Children with biotinidase deficiency cannot cleave biocytin and, therefore, cannot recycle biotin. Untreated individuals become secondarily biotin deficient, which in turn results in decreased activities of the biotin-dependent carboxylases and the subsequent accumulation of toxic metabolites causing clinical symptoms. Biotinidase deficiency is characterized by neurological, cutaneous manifestations and metabolic abnormalities. The worldwide incidence of profound biotinidase deficiency has been estimated at 1:112,271. The human biotinidase gene is located on chromosome 3p25 and consists of four exons with a total length of 1629 base pairs. To date, more than 100 mutations in the biotinidase gene known to cause biotinidase deficiency have been reported. The vast majority of mutations are homozygous or compound heterozygous. Finding known mutations can be correlated with the biochemical enzymatic results. This report summarizes the demographic features of patients identified as biotinidase deficient from August of 2012 through August of 2013 and mutation analysis results for 20 cases in the southeast region of Turkey.

Transient nephrogenic diabetes insipidus caused by fetal exposure to haloperidol.

Haloperidol is commonly used in the treatment of psychiatric disorders. Data from animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in high doses. For the first time, we report a neonate with transient nephrogenic diabetes insipidus (DI) caused by fetal exposure to haloperidol. The magnitude of risk associated with the use of haloperidol during pregnancy appears to be small, but nephrogenic DI secondary to haloperidol is a serious condition with the risk of hypernatremic dehydration. Haloperidol can have adverse effects on the fetus and newborn infant, that's why one should prevent the use of haloperidol during pregnancy and lactation.

Severe renal failure and hyperammonemia in a newborn with propionic acidemia: effects of treatment on the clinical course.

Neonatal-onset propionic acidemia (PA), the most common form, is characterized by poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, and can progress to coma if not identified and treated appropriately. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Herein, we report a case of 3-day-old neonate with PA presented with acute renal failure and metabolic acidosis was effectively treated by peritoneal dialysis and conventional methods.

Serum leptin levels in asthmatic children treated with an inhaled corticosteroid.

BACKGROUND: Recent observations suggest the presence of an interaction between leptin and the inflammatory system; however, there is no adequate knowledge about the role of leptin in atopic states such as asthma. OBJECTIVES: To evaluate the potential role of leptin in relation to bronchial asthma and inhaled corticosteroid therapy. METHODS: Twenty-three children with mild-to-moderate, newly diagnosed asthma enrolled in this 2-period trial. The control group consisted of 20 age- and sex-matched children. Serum leptin levels were measured in patients at initiation and after 4 weeks of budesonide treatment and were compared with control group measurements. RESULTS: Asthmatic children had higher mean +/- SD serum leptin levels at admission (19.3 +/- 5.1 ng/mL) than after budesonide treatment (10.6 +/- 1.6 ng/mL) and vs control group measurements (9.8 +/- 1.6 ng/mL) (P < .001). There was a significant correlation between serum leptin levels before and after budesonide treatment (r = 0.68; P = .007). Mean +/- SD body mass indices in patients and controls were 16.7 +/- 2.1 and 16.9 +/- 2.6 kg/m2, respectively. Serum leptin levels did not correlate with body mass indices before budesonide treatment in the study group (r = -0.13; P = .65) but correlated well after budesonide treatment (r = 0.58; P = .009) and in the control group (r = 0.65; P = .008). CONCLUSIONS: The role of leptin elevation in children with asthma might be a regulatory mechanism rather than being etiologic, but a question may be raised whether it is possible that leptin may contribute to poor patient outcomes. Further research, both basic and clinical, is essential to explain the exact mechanism.

Relationship among serum selenium levels, lipid peroxidation, and acute bronchiolitis in infancy.

Thirty-four infants with acute bronchiolitis and 25 age-matched healthy controls were enrolled to investigate the possible relationship between serum malondialdehyde (MDA) and selenium (Se) levels and the occurrence and severity of acute bronchiolitis in children. Serum samples were taken for serum Se and MDA measurements, and the clinical score was assessed at admission. Blood was taken again from the children with bronchiolitis at 2 mo after discharge from the hospital. Mean serum MDA levels were significantly higher in patients with acute bronchiolitis than at the postbronchiolitis stage and the controls (4.2+/-2.5 nmol/L, 1.4+/-0.8 nmol/L, and 0.7+/-0.2 nmol/L, respectively [p<0.001]). Infants with bronchiolitis had lower mean serum Se levels at the acute stage than after 2 mo (31.7+/-28.9 micro g/L versus 68.4+/-26.4 micro g/L, p<0.05, respectively); both of which were significantly lower than the control group measurements (145.0+/-21.9 micro g/L) (p<0.001). There was a negative correlation between serum MDA and Se levels in the patient group (r= -0.85, p<0.001). The age of the patient, child's immunization status, parental smoking habit, and family crowding index were not correlated with serum Se, MDA levels, or clinical score at admission. In conclusion, increased MDA levels and impaired Se status demonstrate the presence of possible relationship of these parameters with pathogenesis of acute bronchiolitis, and antioxidant supplementation with Se might be thought to supply a beneficial effect against bronchiolitis.