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Creatine is the main source of energy for the brain. Primary creatine deficiency syndromes (PCDSs) are inborn error of metabolism of creatine synthesis. Symptoms of central nervous system involvement are the most common clinical manifestations in these disorders. We reviewed medical records of all genetically confirmed patients diagnosed by whole exome sequencing who were referred to Myelin and Neurodegenerative Disorders Clinic, Children’s Medical Center, Tehran, Iran, from May 2016 to Dec 2018. A literature review was conducted on clinical and genomic variability of PCDS to compare our patients with previously reported cases. We report two patients with creatine deficiency among a cohort of 550 registered cases out of which 200 patients had a genetically confirmed neurodegenerative disorder diagnosis. The main complain in the first patient with creatine transporter (CRTR) deficiency was seizure and genetic study in this patient identified a novel hemizygote variant of “c.92 > T; p.Pro31Leu” in the first exon of SLC6A8gene. The second patient with guanidinoacetate methyltransferase (GAMT) deficiency had an unknown motor and speech delay as the striking manifestation and molecular assay revealed a novel homozygote variant of “c.134G > A; p.Trp45*” in the first exon of GAMTgene. PCDSs usually are associated with nonspecific neurologic symptoms. The first presented case had a mean delayed diagnosis of 5 years. Therefore, in children with unexplained neurologic features including developmental delay and/or regression, mental disability and repeated seizures without any significant findings in metabolic studies, PCDSs can be considered as a differential diagnosis and molecular analysis can be helpful for the precise diagnosis and treatment.

After the onset of type 1 diabetes mellitus (T1DM), preservation of the residual ß-cell function can help good metabolic control. The aim of this study was to evaluate the effect of vitamin D and its receptor gene polymorphisms on residual ß-cells function.

Background: After the onset of type 1 diabetes mellitus (T1DM), preservation of the residual ß-cell function can help good metabolic control. The aim of this study was to evaluate the effect of vitamin D and its receptor gene polymorphisms on residual ß-cells function. Methods: One hundred and one children with T1DM (new cases) older than 5 years were selected. Vitamin D receptor (VDR) gene polymorphisms, vitamin D (VD), fasting and stimulated C-peptide (FCP and SCP) levels were measured within 1.5 and 4.5 month after the diagnosis of disease. Kruskal-Wallis and Mann-whitney U test were used for comparing the study groups. Generalized estimating equation (GEE) model was used for the estimation of association between VD and VDR gene polymorphisms with FCP and SCP after adjustment for comorbid variables. Results: The most frequent genotypes and alleles in TaqI, FokI, BsmI and ApaI polymorphisms were TT (50%) and allele T (68.88%), FF (59.2%) and allele F (77.04%), Bb (41.8%) and allele b (61.73%), and Aa (53.1%) and allele A (63.29%) respectively. In children with higher VD levels, the C-peptide (CP) levels were elevated. Also we observed: the tt genotype associated with increasing SCP levels compared with TT genotype; the bb and Bb genotypes were associated with increasing both FCP and SCP in comparison to BB; and the aa and Aa genotypes were associated with decreasing FCP in comparison to the AA genotype. Conclusions: Sufficient levels of VD (more than 30 ng/ml) can preserve residual ß-cells and insulin secretion.