Objectives: Hypotonia, lethargy, eczema, alopecia, conjunctivitis, ataxia, hearing loss, optic atrophy, cognitive retardation, and seizures can occur in patients with biotinidase deficiency, and it is inherited as autosomal recessive. The aim of this study was to evaluate the cases followed up with the diagnosis of biotinidase deficiency in our unit, in terms of clinical, biochemical and genetic analyses. Methods: A total of 112 cases followed up in our centre with the diagnosis of biotinidase deficiency between August 2018–September 2020 were included in the study. Data were collected retrospectively. Results: A total of 112 cases (55.4% male, mean age: 2.2 ± 2.8 years) diagnosed with biotinidase deficiency were evaluated. Diagnoses were made by newborn screening in 90.2% of the cases, by family screening in 4.5%, and by investigating symptoms in 5.4%. The most frequently (27.5%) detected mutations were c.1330G>C (p.D444H)/c.1330G>C (p.D444H) homozygous mutation, followed by (13.0%) c.1330G>C (p.D444H)/c.470G>A (p.R157H) compound heterozygous mutation, and (13.0%) c.470G>A (p.R157H)/c.470G>A (p.R157H) homozygous mutation. Biotinidase enzyme levels were found to be higher in patients with the p.D444H homozygous mutation than patients with other mutations. Biotin treatment was started in all patients with enzyme deficiency. Conclusions: Since the treatment is inexpensive and easily available, it is vital to detect this disease before symptom onset, especially findings related to the central nervous system, hearing and vision loss. In patients diagnosed with enzyme deficiency, the diagnosis should be definitively confirmed by genetic analysis.

Increased intestinal permeability (IIP) precedes several autoimmune disorders. Although Hashimoto's thyroiditis (HT) is the most common autoimmune disorder, the role of HP in its pathogenesis had received little attention. Zonulin plays a critical role in IIP by modulating intracellular tight junctions. Rise of serum zonulin levels were shown to indicate HP in human subjects. In this case-control study, we examined the hypothesis that patients with HT have IIP. We studied 30 children and adolescents with HT, and 30 patients with congenital hypothyroidism (CH) matched for age, gender and body mass index (BMI). Serum zonulin levels, free thyroxine (fT4), thyroid stimulating hormone (TSH), anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were measured. Zonulin levels were significantly higher in patients with HT than patients with CH (59.1 +/- 22.9 ng/mL vs. 43.3 +/- 32.9 ng/mL, p = 0.035). In patients with HT, zonulin levels were positively correlated with weight (r = 0.406, p= 0.03), BMI (r = 0.486, p = 0.006) and levothyroxine dose (r = 0.463, p = 0.02). In patients with CH, zonulin levels were positively correlated with age (r = 0.475, p = 0.008), weight (r = 0.707, p< 0.001), BMI (r =0.872, p <0.001) and levothyroxine dose (r =0.485, p = 0.007). After adjusting for age, weight, TSH and fT4 levels, serum zonulin was only associated with levothyroxine dose in patients with HT (R-2 =0.36, p =0.05). In patients with CH, only weight was associated with zonulin levels (R-2 =0.62, p <0.001). In conclusion, higher zonulin levels in children and adolescents with HT suggested IIP in these patients. Additionally, the association between zonulin levels and levothyroxine dose might imply a relationship between serum zonulin and disease severity.

Objective: To assess the incidence of type I diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9. 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6 %) were girls and 911 (51.4%)were boys. The mean age at diagnosis was 9.2 +/- 4.2 years and it was not significantly different between girls (9.0 +/- 4.1 years) and boys (9.4 +/- 4.4 years) (p = 0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/1 00.000 respectively. The incidence of T1DM was similar over the course of three years (p = 0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.

Background: As K-ATP channel mutations are the most common cause of neonatal diabetes mellitus (NDM) and patients with these mutations can be treated with oral sulfonyl-ureas, empiric therapy is a common practice for NDM patients. Case presentation: A non-syndromic, small for gestational age baby born to first-degree consanguineous parents was diagnosed with NDM. Because of hypo-and hyperglycemic episodes and variability in insulin requirement, we initiated a trial of glibenclamide, with a presumptive diagnosis of NDM caused by a K-ATP channel mutation. However, this empiric sulfonylurea trial did not improve the patient's glycemic control and resulted in resistance to exogenous insulin. Genetic testing identified a previously reported homozygous INS promoter mutation (c.-331C>G), which was not responsive to sulfonylurea therapy. Conclusions: In light of our results, we recommend to confirm the genetic diagnosis as soon as possible and decide on sulfonylurea treatment after a genetic diagnosis is confirmed.

Objectives Classic galactosemia is a galactose metabolism disorder due to galactose-1-phosphate uridyltransferase deficiency. In this study we report the clinical features of a cohort of children with classic galactosemia. Methods A retrospective evaluation was made of the files of 42 cases followed up for a diagnosis of classic galactosemia between January 2000 and December 2021. The data were collected of clinical, laboratory and genetic characteristics. Results The cases comprised of 25 (59.5%) girls and 17 (40.5%) boys with a median age of 15 days (range, 1 day to 9 years) at diagnosis. In addition, thirty-six cases (92.3%) could be diagnosed before they were 4 months old by hospitalization with various clinical findings, primarily liver dysfunction. The most common complaints on presentation were jaundice (78.4%) and vomiting (27%) and the most frequently seen genetic pathogenic variant was c.563A>G (p.Gln188Arg) (92.4%). Conclusions It can be emphasized that there is a need for a neonatal screening program for classic galactosemia to be able to increase the possibility of early diagnosis and to be able to start treatment before the development of a severe clinical picture.

Background/Objectives: Cerebral folate transporter deficiency is characterized by pauses and regression in general development stages, with ataxia, choreoathetoid movements, and myoclonic epilepsy generally resistant to treatment. The aim of this study was to comprehensively evaluate cases followed up in two centres in Türkiye for a diagnosis of folate receptor-α deficiency. Methods: The study included nine cases from six different families. Results: The patients comprised 22.2% males and there was parental consanguinity in 88.9% of cases. The mean age at which complaints were first noticed was 3.7 years, and the age of definitive diagnosis was 10.4 years. The most frequently seen first complaints were febrile convulsions and attention deficit-hyperactivity-learning difficulties. The diagnosis most commonly made before the definitive diagnosis was epilepsy, and the first seizure occurred at a mean of 5.2 years. On cranial imaging, white matter involvement, cerebellar atrophy and cerebral atrophy were determined most often. Definitive diagnosis was established solely through clinical findings and genetic analysis. Three different variants in the FOLR1 gene were determined. Treatment with folinic acid at a dose of 5.2 mg/kg/day of PO was started at the age of 9.8 years on average, and intravenous folinate was started at different doses. Conclusions: This study stands out as one of the largest case series in the literature and identifies a previously unreported novel variant. Our study suggests that FOLR1-related CFD should be considered in cases with febrile convulsions, developmental delay, ataxia, autism spectrum disorder, acquired microcephaly, and MRI findings of white matter involvement and cerebellar atrophy. Due to an asymptomatic early period, CFD diagnosis may be delayed, and treatment after symptom onset may be less effective. Incorporating FOLR1 gene analysis into newborn screening programmes could facilitate early diagnosis and treatment. It is thought that the application of vagus nerve stimulation, in addition to folinic acid and anticonvulsant drug treatment, could be effective in seizure control.