Not All Diabetic Ketoacidosis in Infant Is Type 1: A Case Report Permanent Neonatal Diabetes.

Background/Objective: Neonatal diabetes is a monogenic type of diabetes mellitus. It arises at the first 6 months of age and can be classified as permanent or transient. There are limited cases of neonates with DKA who have heterozygous mutations in INS and PKHD1 genes, especially in Saudi Arabia. We present a case of neonatal diabetes with diabetic ketoacidosis (DKA) born to consanguineous parents in Saudi Arabia. This study aims to highlight the importance of the genetic mutations associated with neonatal diabetes and identify the clinical manifestation features of neonatal diabetes. Case Report: A six-month-old boy born to consanguineous parents with a family history of neonatal diabetes was diagnosed with DKA. The case was presented to the emergency department (ED) with vomiting and increased urination for 3 days. The child showed signs of severe dehydration and severe metabolic acidosis with a high anion gap and elevated hemoglobin A1C level (16.3%) was reported. According to the genetic test, the patient had an INS and PKHD1gene mutation. The treatment was initiated according to the DKA protocol, and then he received subcutaneous insulin. Discussion: Neonatal diabetes is a condition caused by several gene mutations. In this case, heterozygous mutations in INS and PKHD1 genes were reported. The type of gene mutation could predict neonatal diabetes type, whether permanent or transient, and its response to treatment. Conclusion: Genetic testing for neonates soon after birth is suggested for the early detection and classification of neonatal diabetes, especially among children with a family history of neonatal diabetes.

Prevalence and Related Risk Factors of Vitamin D Deficiency in Saudi Children with Epilepsy.

BACKGROUND: Vitamin D has a role in the pathogenesis of many medical disorders, especially those of the central nervous system. It is essential in maintaining the bone health of children. However, patients with epilepsy are at high risk of developing vitamin D deficiency due to antiseizure medications (ASMs). Therefore, we aimed to assess the prevalence of vitamin D deficiency and related risk factors in children with epilepsy. METHODS: This is the baseline report of a pragmatic, randomized, controlled, open-label trial that assessed the impact of vitamin D supplementation in preventing vitamin D deficiency (NCT03536845). We included children with epilepsy aged 2-16 years who were treated with ASMs from December 2017 to March 2021. Children with preexisting vitamin D metabolism problems, vitamin-D-dependent rickets, malabsorption syndromes, renal disease, and hepatic disease were excluded. The baseline demographic data, anthropometric measurements, seizure types, epilepsy syndromes, ASMs, and seizure control measures were recorded. Blood tests for vitamin D (25-hydroxyvitamin D [25(OH)D), serum calcium, serum phosphorus, and parathyroid hormone levels were performed. Based on vitamin D concentration, patients were categorized as deficient (<50 nmol/L), insufficient (74.9-50 nmol/L), or normal (>75 nmol/L). RESULTS: Of 159 recruited children, 108 (67.92%) had generalized seizures, 44 (27.67%) had focal seizures, and 7 (4.4%) had unknown onset seizures. The number of children receiving monotherapy was 128 (79.0%) and 31 (19.1%) children were receiving polytherapy. The mean vitamin D concentration was 60.24 ± 32.36 nmol/L; 72 patients (45.28%) had vitamin D deficiency and 45 (28.3%) had vitamin D insufficiency. No significant difference in vitamin D concentration was observed between children receiving monotherapy and those receiving polytherapy. The main risk factors of vitamin D deficiency were obesity and receiving enzyme-inducer ASMs. CONCLUSIONS: The prevalence of vitamin D deficiency was high among children with epilepsy. Obese children with epilepsy and those on enzyme-inducer ASMs were at increased risk for vitamin D deficiency. Further studies are needed to establish strategies to prevent vitamin D deficiency.

Novel Homozygous CYP27B1 Gene Mutation in Vitamin D-Dependent Rickets Type 1A (VDDR1A) Disorder: A Case Report.

Background: Vitamin D-dependent rickets type 1A (VDDR1A) rickets is an uncommon kind of rickets that affects both boys and girls. Children with mutations are normal at birth and present at around 6 months to 2 years of age with symptoms. When suspected, genetic testing is required to confirm the diagnosis. Case Presentation: This is a case report of VDDR1A in a 4-year-old boy who presented with delayed growth, inability to stand, and rachitic bone deformities. The diagnosis was reached by anthropometric measurement, bone profile, and radiological studies, then confirmed by genetic testing, which revealed a homozygous pathogenic variant in the CYP27B1 gene. He was treated with Vitamin-D (alfacalcidol) and oral calcium. Conclusion: VDDR1A is caused by a mutation in the CYP27B1 gene, which impairs the 1 hydroxylase enzyme, which compromises vitamin-D production.

A Novel TBX1 Variant Causing Hypoparathyroidism and Deafness.

BACKGROUND: The TBX1 gene encodes the T-box 1 protein that is a transcription factor involved in development. Haploinsufficiency of the TBX1 gene is reported to cause features similar to DiGeorge syndrome. The TBX1 gene is located within the DiGeorge syndrome region, and studies support that the TBX1gene is responsible for most of the features of the phenotype of hemizygous deletion of chromosome 22q11.2. In this study, we report a family of 4 (a father with 3 children) who presented with congenital hypoparathyroidism and hypocalcemia, facial asymmetry, deafness, normal intelligence, and no cardiac involvement. METHODS: We performed whole genome sequencing, computational structural analysis of the mutants, and gene expression studies for all affected family members. RESULTS: Whole genome sequencing revealed a paternal inherited novel heterozygous variant, c.1158_1159delinsT p.(Gly387Alafs*73), in the exon 9 isoform C TBX1 gene, causing a loss of nuclear localization sequence (NLS) and transactivation domain (TAD) with no change in gene expression and resulted in a DiGeorge-like phenotype. CONCLUSION: A pathogenic variant in the TBX1 gene exon 9 C that predicted to cause a loss in the NLS region and most of TAD leads to variable features of hypoparathyroidism, distinctive facial features, deafness, and no cardiac involvement. In addition, our report and previous reports indicate the presence of a wide phenotypic spectrum of TBX1 genetic variants and the consistent absence of cardiac involvement in the case of pathogenic variants on exon 9 isoform C TBX1 gene.