Comparison of Treatment Regimens in Management of Severe Hypercalcemia Due to Vitamin D Intoxication in Children

Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level >10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level >150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61%) from 11 centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15±3.2 mg/dL, 5.2±1.2 mg/dL, 268±132 IU/L, 322 (236-454) ng/mL, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (rs=0.402, p<0.001). Patients were designated into five groups according to the initial specific treatment regimens (hydration-only, prednisolone, alendronate, pamidronate, and combination). Need for another type of specific drug treatment was higher in children who initially received prednisolone (p<0.001). Recurrence rate of hypercalcemia was significantly lower in children who were treated with pamidronate (p=0.02). Conclusion: Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens should be considered.

Glutaric Acidemia Type 1: A Case of Infantile Stroke.

BACKGROUND: Glutaric acidemia Type 1 (GA-1) is an autosomal recessively inherited metabolic disorder which is associated with GCDH gene mutations which alters the glutaryl-CoA dehydrogenase, an enzyme playing role in the catabolic pathways of the amino acids lysine, hydroxylysine, and tryptophan. Clinical findings are often encephalopathic crises, dystonia, and extrapyramidal symptoms. CASE REPORT: A 9-month-old male infant referred to our department with focal tonic-clonic seizures during rotavirus infection and acute infarcts in MRI. Clinical manifestation, MRI findings, and metabolic investigations directed thoughts towards GA-I. Molecular genetic testing revealed a homozygous c.572T>C (p.M191T) mutation in GCDH gene which confirmed the diagnosis. Application of protein restricted diet, carnitine and riboflavin supplementations prevented the progression of Magnetic Resonance Imaging (MRI) and clinical pathologic findings during the 1 year of follow-up period. CONCLUSION: This case is of great importance since it shows possibility of infantile stroke in GA-1, significance of early diagnosis and phenotypic variability of disease.

Evaluation of vitamin D prophylaxis in 3-36-month-old infants and children.

BACKGROUND: Vitamin D (VD) deficiency (VDD) is still a population-based health problem that affects people at different ages. The aim of this study was to evaluate VD prophylaxis for the prevention of VDD in (3-36)-month-old infants and children. METHODS: Infants and children aged between 3 and 36 months, with different etiologies, admitted to outpatient and inpatient clinics from October 2010 to October 2011 at the Children's Hospital of Erciyes University, were enrolled for the study. Their VD intake (if used; time of initiation, dosage and compliance) and nutritional status (breast-fed, formula or complementary fed) were noted. In order to study seasonal VD changes, the levels of serum calcium, phosphorus and magnesium, alkaline phosphatase activity (PLA), plasma parathyroid hormone (PTH) and 25 hydroxyvitamin 25(OH)D levels were measured at the beginning of VD supplementation during the four seasons. RESULTS: A total of 316 subjects were enrolled in the study, consisting of 202 (63.9%) outpatient and 114 (26.1%) inpatient groups. From these subjects, 304 (96.2%) were supplemented with VD; whereas 12 (3.8%) were not. Out of the subjects supplemented with VD, 237 (75%) initiated VD after the second week of life, 267 (87.8%) were given three drops of VD daily and 209 (66.1%) had taken VD regularly. The plasma 25(OH)D levels were found to be lower in the inpatient group than the outpatient group (29.35 ng/mL and 34.35 ng/mL, respectively). The plasma 25(OH)D levels were lower during the spring and winter. VDD and VD insufficiency (VDI) was found in 31 (9.8%) and 30 (9.5%) subjects, respectively. CONCLUSIONS: The plasma 25(OH)D levels were lower in inpatient and breast-fed only subjects and in winter and spring. The national VD augmentation program seems to be beneficial for the prevention of VDD, but VDD/VDI seems to still be an important health problem.

Does early treatment prevent deafness in thiamine-responsive megaloblastic anaemia syndrome?

Thiamine-responsive megaloblastic anaemia (TRMA; OMIM 249270) syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anaemia, and sensorineural deafness. Progressive hearing loss is one of the cardinal findings of the syndrome and is known to be irreversible. Whether the deafness in TRMA syndrome can be prevented is not yet known. Here, we report a four-month-old female infant diagnosed with TRMA syndrome at an early age. There was no hearing loss at the time of diagnosis. The patient's initial auditory evoked brainstem response measurements were normal. Although she was given thiamine supplementation regularly following the diagnosis, the patient developed moderate sensorineural hearing loss at 20 months of age, indicating that early diagnosis and treatment with oral thiamine (100 mg/day) could not prevent deafness in TRMA syndrome. It would be premature to draw general conclusions from one case, but we believe that further patient-based observations can shed light on the pathophysiology of this rare syndrome as well as prediction of its prognosis.

Thiamine withdrawal can lead to diabetic ketoacidosis in thiamine responsive megaloblastic anemia: report of two siblings.

Thiamine responsive megaloblastic anemia syndrome (TRMA), an autosomal recessive disorder caused by the deficiency of thiamine transporter protein, is the association of diabetes mellitus, anemia and deafness. Pharmacological dose thiamine normalizes hematological abnormalities and their effects on the course of diabetes mellitus. We report on 8 years follow up of two siblings with TRMA. They presented in the prepubertal period with diabetic ketoacidosis due to lack of thiamine supplementation for 2 months. Their insulin requirements fell rapidly and disappeared with thiamine therapy. Hematological parameters normalized within 30 days. The diabetic picture is responsive to thiamine treatment in patients with TRMA. Insulin dependent diabetes may occur throughout the pubertal period. If thiamine supplementation is not sufficient, ketoacidosis may develop in patients during the prepubertal period.

Iodine and selenium deficiency in school-children in an endemic goiter area in Turkey.

Endemic goiter is one of the most important health problems in Turkey. However, there are not enough studies associated with iodine and selenium status. This study was carried out to establish the effects of iodine and selenium levels on thyroid gland size and thyroid functions in 73 healthy school-children, 7-12 years old (mean 9.56 +/- 1.77 years), 38 girls (52%) and 35 boys (48%), living in an endemic goiter area. Goiter was found in 32 of the children (43.8%) by palpation, and 56 of the children (76.7%) by ultrasonography. Mean serum T3 and TSH levels were in the upper limit of normal, and mean serum T4 levels were within the normal limits, but mean serum thyroglobulin levels were higher than the normal limits. Mean serum selenium level was 30.84 +/- 23.04 microg/l, and mean urinary iodine level was 3.91 +/- 3.77 microg/dl, appropriate for moderate iodine and selenium deficiency. Thyroid volumes of the children were negatively correlated with serum selenium levels, but there was no correlation with urinary iodine levels and thyroid hormones. In conclusion, school-children in this area had significant goiter problems, probably due to the iodine and selenium deficiencies.

Insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels of children living in an iodine- and selenium-deficient endemic goiter area.

Serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were investigated in 31 children living in an endemic goiter area and 33 healthy subjects living in an nonendemic area. Serum IGF-I and IGFBP-3 levels of iodine- and selenium-deficient children were found to be lower than those of control subjects (p<0.001). There was a positive correlation between the IGF-I with chronological age and body mass index. There was also positive correlation between the IGF-I and IGFBP-3. No significant difference was found between the goitrous and nongoitrous children. These results suggest that IGF-I and IGFBP-3 levels are affected by thyroid dysfunction as a result of iodine and selenium deficiency. However, IGF-I and IGFBP-3 levels are not associated with goiter.