The incidence of succinic semialdehyde dehydrogenase (SSADH) deficiency, an autosomal recessive inherited disorder of GABA degradation, is unknown. Upon a recent diagnosis of a new family of affected fraternal twins from the Punjabi ethnic group of India, case ascertainment from the literature and our database was done to determine the number of confirmed cases along with their geographic distribution. The probands presented with global developmental delay, infantile onset epilepsy, and a persistent neurodevelopmental disorder upon diagnosis at 10 years of age with intellectual disability, expressive aphasia, and behavioral problems most prominent for hyperactivity. Gamma-hydroxybutyric aciduria and homozygous ALDH5A1 c.608C>T; p.Pro203Leu mutations were confirmed. Identification of all available individual cases with clinical details available including geographic or ethnic origin revealed 182 patients from 40 countries, with the largest number of patients reported from the USA (24%), Turkey (10%), China (7%), Saudi Arabia (6%), and Germany (5%). This study provides an accounting of all published cases of confirmed SSADH deficiency and provides data useful in planning further studies of this rare inborn error of metabolism.

Classical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria, 16 children below the age of 18 years were evaluated by Sanger sequencing of the coding exons of CBS gene with flanking intronic regions. The common C677T variant of the MTHFR gene was also screened by restriction fragment length polymorphism. Fifteen children were clinically suspected of having classical homocystinuria and one asymptomatic child with positive family history. Only seven children had biochemical features of classical homocystinuria. Sanger sequencing of the CBS gene confirmed 15 different pathogenic or likely pathogenic variants in 14 cases. Of these, seven variants were novel (three frameshift deletions, two nonsense, one missense, one splice site variant) and were predicted to be deleterious by Mutation Taster software. Seven cases were homozygous, another six were compound heterozygous, and one case was single heterozygous in the study. None of the three most frequent mutations reported worldwide viz., I278T, G307S, and IVS 11-2A>C were found in our cohort. No variants were detected in the exons 2, 8, 12, and 14 as compared to reported literature. Eleven out of 15 variants were associated with the conserved catalytic domain of the CBS polypeptide. The MTHFR polymorphism C677T was observed in heterozygous state in six cases. Our study reports the detailed genotype and seven novel variants in the CBS gene, causing classical homocystinuria in Indian children. The genetic analysis will help to offer accurate genetic counseling, prenatal diagnosis, and development of mutation-based novel therapeutic strategies.

Background: Daily administration of thyroxine has proven efficacy in treatment of children with hypothyroidism. However, the possibility of treatment with longer dosing intervals that offers flexibility and choice in maintaining euthyroid state has not been tested in children. Objectives: To study the efficacy of an alternate day regimen to maintain euthyroidism in children with congenital hypothyroidism Patients and Methods: Forty patients given alternate day therapy, while 30 children continued on their daily regimen were followed up at monthly intervals for 3 months. Clinical and laboratory assessments were performed at each follow up visit. Results: The clinical and anthropometric parameters remained similar in both groups of patients during the study indicating a maintained euthyroid state clinically. The thyroid profiles also remained within normal limits suggesting biochemical euthyroidism status with alternate day therapy. However the baseline serum aminotransferase levels showed mild elevation in patients on alternate day regimen and the difference persisted during the follow up visits. Higher HDL and lower TC and LDL levels suggested some beneficial effect of alternate day schedule on lipid profiles. Conclusions: In short-term, alternate day schedule can be effectively used to maintain clinical and biochemical euthyroid state in children with congenital hypothyroidism beyond 4 years of age. Keywords: Hypothyroidism; Thyroxine; Children

Various prenatal and postnatal factors such as gestational age, mode of delivery, sex, antibiotic exposure, feeding type, duration of feed and other exposures associated with the hospital environment can drive the formation of gut microbiota. In the current study, we examined the role of all these factors in the gut microbiota of healthy Indian preterm infants admitted to NICU in the first four weeks of life. Preterm neonates admitted to the NICU from April 2023 and October 2023 were recruited and fecal samples were collected weekly once beginning from the seventh day till the 30th day of life. 16s rRNA gene sequencing was performed on the NovaSeq 6000 platform. The PICRUSt2 tool was used to predict the functional profiles of the gut microbiome. A total of 61 samples were collected from 16 preterm infants. Alpha and beta diversity showed the administration of probiotics, postnatal age, mode of delivery, and sex of infants as major contributors to altered microbial diversity in preterm infants. The MaAsLin2 analysis showed that the supplementation of probiotics increased Bifidobacterium levels. PICRUSt2 analysis revealed that probiotic supplementation increased the bacterial genes responsible for bile acid metabolism and glycosphingolipid synthesis. Probiotics and postnatal age are responsible for alterations of the gut microbial composition in healthy preterm infants.