EPIMERASE DEFICIENCY GALACTOSEMIA: A CASE REPORT

WOS: 000307513100289

Thyroid hormone levels and their relationship to survival in children with bacterial sepsis and septic shock

WOS: 000225158700010PubMed ID: 15526723Objectives: Reported studies have showed alternations of thyroid hormones in critical illness mostly in adults and some in children. In this study, we aimed to measure thyroid hormone levels in children with sepsis and septic shock and investigate the relationship of these hormones with clinical state and survival. Patients and Methods: Thyroid hormone levels of children with sepsis and septic shock, and age-and sex-matched controls were measured. Results. There were 51 children in sepsis (group S), 21 children in septic shock (group SS) and 30 in the control (group C) group. Total triiodothyronine (TT3) levels were (nmol/l): 6.91 +/- 0.22, 0.64 +/- 0.23, 2.11 +/- 0.59; free triiodothyronine (FT3) (pmol/l): 0.027 +/- 0.006, 0.018 +/- 0.007, 0.049 +/- 0.010; total thyroxine (TT4) (nmol/l): 100.62 +/- 21.93, 65.79 +/- 19.35, 109.65 +/- 19.35; free thyroxine (FT4) (pmol/l): 18.06 +/- 3.87, 10.32 +/- 1.29, 19.35 +/- 3.87; and thyroid stimulating hormone (TSH) (mIU/ml): 5.0 +/- 2.0, 4.8 +/- 2.4, 5.2 +/- 3.0, in children with sepsis, septic shock, and controls, respectively. The TT3, FT3, TT4, and FT4 levels of group SS were significantly lower than those of groups S and C. The TT3 and FT3 levels of group S were lower than in group C, but there was no significant difference between TT4, and FT4 levels of groups S and C. TSH levels were slightly decreased in both sepsis and septic shock, but the difference was not significant. Eleven (21.6%) children with sepsis and 15 (71.4%) children with septic shock died (p <0.001). The levels of TT3, FT3, TT4 and FT4 were markedly lower in non-survivors of groups S and SS compared to survivors (p <0.001). Conclusions: These changes in the hypothalamopituitary-thyroidal axis may suggest a possible prognostic value of thyroid hormone levels in children with sepsis and septic shock. To the best of our knowledge, this report is the first study to compare thyroid hormone levels in a large number of patients with sepsis and septic shock with those in healthy controls in childhood

Thyroid peroxidase gene mutations causing congenital hypothyroidism in three Turkish families

In Turkey congenital hypothyroidism (CH) occurs with a prevalence of one in 2,736 newborns while the worldwide incidence is one in 3,000-4,000 newborns. 85-90% of these cases are due to dysgenesis of the thyroid gland, whereas defects in thyroid hormone synthesis account for 10-15%. The majority of patients with dyshormonogenesis have a defect in thyroid peroxidase (TPO). To date, more than 60 different mutations have been described in the TPO gene, mostly single nucleotide substitutions. Five children from three consanguineous families were diagnosed with CH on the basis of clinical symptoms and signs - goiter, macroglossia and prolonged jaundice at newborn age. Two different mutations in the TPO gene were identified. Affected children in families I and II had a nonsense mutation in exon 10 (R540X). Genotyping of polymorphic markers within the TPO gene revealed that these families shared a common haplotype, suggesting a founder effect. In the third family, a novel mutation (G319R) in exon 8 was identified. © Freund Publishing House Ltd

TYROSINEMIA TYPE 1 AND NEUROGENIC CRISIS: A CASE REPORT

WOS: 000307513100082

Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-beta gene: Phenotypic variability and founder effect

WOS: 000223072400081PubMed ID: 15292359Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis. Age at diagnosis and clinical phenotype were variable. All affected children carried an identical homozygous splice site mutation (IVS2 + 5 Gdouble right arrowA) in the TSHbeta gene. This mutation leads to skipping of exon 2 and a loss of the translational start codon without ability to produce a TSH-like protein. However, using specific monoclonal antibodies, we detected a very low concentration of authentic, heterodimeric TSH in serum, indicating the production of a small amount of correctly spliced TSH mRNA. By genotyping all family members with polymorphic markers at the TSHbeta locus, we show that the mutation arose on a common ancestral haplotype in three unrelated Turkish families indicating a founder mutation in the Turkish population. These results suggest that this TSHbeta mutation is among the more common TSHbeta gene mutations and stress the need for a biochemical and molecular genetic workup in children with symptoms suggestive of congenital hypothyroidism, even when the neonatal TSH screening is normal.NIDDK NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [DK 00055, DK 15070

Four new cases of congenital secondary hypothyroidism due to a splice site mutation in the thyrotropin-ß gene: Phenotypic variability and founder effect

PubMedID: 15292359Isolated TSH deficiency is a rare cause of congenital hypothyroidism. We here report four children from two consanguineous Turkish families with isolated TSH deficiency. Affected children who were screened at newborn age had an unremarkable TSH result and a low serum TSH level at diagnosis. Age at diagnosis and clinical phenotype were variable. All affected children carried an identical homozygous splice site mutation (IVS2 + 5 G › A) in the TSHß gene. This mutation leads to skipping of exon 2 and a loss of the translational start codon without ability to produce a TSH-like protein. However, using specific monoclonal antibodies, we detected a very low concentration of authentic, heterodimeric TSH in serum, indicating the production of a small amount of correctly spliced TSH mRNA. By genotyping all family members with polymorphic markers at the TSHß locus, we show that the mutation arose on a common ancestral haplotype in three unrelated Turkish families indicating a founder mutation in the Turkish population. These results suggest that this TSHß mutation is among the more common TSHß gene mutations and stress the need for a biochemical and molecular genetic workup in children with symptoms suggestive of congenital hypothyroidism, even when the neonatal TSH screening is normal

Serum IL-1, IL-2, TNF alpha and INF gamma levels of patients with type 1 diabetes mellitus and their siblings

WOS: 000184293800010PubMed ID: 12713258Type 1 diabetes mellitus (DM) develops as a result of autoimmune destruction of the pancreatic beta-cells. The aim of this study was to explore possible associations between serum levels of cytokines, IL-1, IL-2, TNFalpha and INFgamma and metabolic parameters in children with type 1 DM and their non-diabetic siblings to determine whether these cytokines could be indicators of disordered immune regulation. The study population consisted of 41 children with type 1 DM, 32 non-diabetic siblings, and 28 healthy controls. Children with DM were divided into three subgroups: 1) newly diagnosed patients with diabetic ketoacidosis (ND + DKA), 2) newly diagnosed patients without DKA (ND - DKA), and 3) previously diagnosed patients (PD). The highest serum IL-1alpha level was found in the ND - DKA group, which was significant compared to both the ND + DKA (p <0.05) and the siblings (S) (p <0.005). IL-2 levels were similar among all groups. The highest TNFalpha level was observed in the ND + DKA group, which was significant against the ND - DKA (p <0.05), PD (p <0.001), S (p <0.05), and: control (C) (p <0.005) groups. TNFalpha concentration in the PD group was significantly lower than those of S (p <0.005) and C (p <0.001) groups. The ND - DKA group had the highest INFgamma and this was statistically significant when compared with the S (p <0.005) and C (p <0.05) groups. Both the newly diabetics and all diabetics as a group had statistically significantly higher INFgamma levels than both the S (p <0.01 for both) and C (p <0.05 for both) groups. In the diabetics as a whole group, TNFalpha showed correlations with INFgamma (r = 0.370, p <0.05). IL-1 showed correlation with TNFalpha (r = 0.368, p <0.05) INFgamma (r = 0.796, p <0.001) and IL-2 (r = 0.862, p <0.001) in the all diabetics group. IL-2 was correlated with TNFalpha (r = 0.320, p <0.05) and INFalpha (r = 0.754, p <0.01) in the all diabetics group. In conclusion, our results suggest that proinflammatory cytokines TNFalpha, INFgamma, IL1alpha and IL-2 may play important roles alone or in combination in the pathogenesis of type 1 diabetes mellitus

Hashimoto's encephalopathy: Four cases and review of literature

PubMedID: 23967879Hashimoto's encephalopathy is a rare clinically heterogenous condition consisting of encephalopathy, seizures and variable neurological and psychiatric manifestations, accompanied by high titres of serum antithyroid antibodies. We described the clinical and laboratory findings of four children (aged 8-17 years) with Hashimoto's encephalopathy. The clinical features of three patients at presentation included refractory epilepsy, and confusion, and one patient presented with behavioral and cognitive changes. During their presentation, two of them were in euthyroid, and the others were in hypothyroid status. All patients manifested increased antithyroid antibodies. Two patients improved with steroid treatment. The others responded to plasmapheresis instead of corticosteroid treatment. Physicians' awareness of this complication is of great importance because most patients respond dramatically to the treatment. Copyright © 2014 Informa Healthcare USA, Inc