Association between Leptin, Adiponectin Levels, and Nutritional Status in Children with Down Syndrome

Background: Children with Down Syndrome (DS) have been associated with obesity. Leptin and adiponectin were also significant predictors of obesity and its comorbidity in DS. However, there was limited data regarding leptin and adiponectin in children with DS, particularly who were undernutrition. This study aimed to seek the role of leptin levels, adiponectin levels, and nutritional status in children with DS. Methods: This cross-sectional study was conducted on 40 children with DS aged 1 - 5 years. Height and weight were measured, and then the growth was interpreted using a DS growth chart. The Weight for Height Z-Score (WHZ) and Height for Age Z-Score (HAZ) were determined, and Mid-Upper Arm Circumference (MUAC) was measured. Leptin and adiponectin serum were analyzed using the enzyme-linked immunosorbent assay (ELISA) method. Mann-Whitney test was done to compare leptin and adiponectin levels in normal and wasted groups, while Spearman’s analysis was carried out to correlate laboratory results and anthropometric parameters. Results: Forty children participated (23 males, 17 females) with a median age was 25.5 months. Ten out of 40 children with DS (25%) were wasted and leptin was significantly lower in wasted compared to normal children. In addition, leptin was significantly correlated with WHZ (r = 0.415; p = 0.008), and MUAC (r = 0.427; p = 0.006), while adiponectin did not significantly correlate with those anthropometric variables in both wasted or non-wasted groups. Conclusion: Leptin is associated with WHZ and MUAC, and it decreases in wasted children with DS

Thyroid Profile of Childhood Tuberculosis Treated with Anti Tuberculosis Drug During Intensive Phase

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis.  The incidence is  10 % in children. Tuberculosis has high morbidity and mortality which needs adequate treatment. The side effects of FDC is thyroid hormone dysfunction which can interfere children's quality of life. However, research about the effect of FDC therapy on thyroid hormone profile in children with TB are very limited. Objective: To determine the effect of anti-tuberculosis drug treatment on thyroid hormone profile in paediatric tuberculosis. Methods: A one group pretest-posttest design study of 50 patients was conducted at the Semarang Health Center for the period January 2021-June 2021. Thyroid function tests of TSH, FT4 and T3, in TB children were measured before FDC therapy and 2 months after administration. The data were analysed descriptively and a comparative test was performed using SPSS 25.Results: There were no significant differences in TSH, FT4 and T3 serum levels before FDC therapy and 2 months of FDC administration. Thyroid hormone levels before treatment and 2 months after administration of FDC, respectively, euthyroid in 44 vs 42 patients.Conclusion: Two months of tuberculosis treatment in children decreased the serum FT4 and T3 level but no changes in the serum TSH level before and after the treatment

X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension, nystagmus, and vision loss due to retinopathy. The course of the disease was slowly progressive. All patients had maternally inherited or de novo mutations in or near exon 7 of AIFM1, within a region of 70 bp, including synonymous and intronic changes. AIFM1 mutations have previously been associated with neurologic presentations as varied as intellectual disability, hearing loss, neuropathy, and striatal necrosis, while AIFM1 mutations in this small region present with a distinct phenotype implicating bone. Analysis of cell lines derived from four patients identified significant reductions in AIFM1 mRNA and protein levels in osteoblasts. We hypothesize that AIFM1 functions in bone metabolism and myelination and is responsible for the unique phenotype in this condition.</p

4H Leukodystrophy: Lessons from 3T Imaging

4H leukodystrophy is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. With its variability in clinical symptoms, application of pattern recognition to identify specific magnetic resonance imaging (MRI) features proved useful for the diagnosis. We collected 3T MR imaging data of 12 patients with mutations in POLR3A ( n = 8), POLR3B ( n = 3), and POLR1C ( n = 1), all obtained at the same scanner. We assessed these images and compared them with previously obtained 1.5T images in 8 patients. Novel MRI findings were myelin islets, closed eye sign, and a cyst-like lesion in the splenium. Myelin islets were variable numbers of small T1 hyperintense and T2 hypointense dots, mostly in the frontal and parietal white matter, and present in all patients. This interpretation was supported with perivascular staining of myelin protein in the hypomyelinated white matter of a deceased 4H patient. All patients had better myelination of the medial lemniscus with a relatively hypointense signal of this structure on axial T2-weighted (T2W) images (“closed eye sign”). Five patients had a small cyst-like lesion in the splenium. In 10 patients with sagittal T2W images, we also found spinal cord hypomyelination. In conclusion, imaging at 3T identified additional features in 4H leukodystrophy, aiding the MRI diagnosis of this entity

X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1.

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension, nystagmus, and vision loss due to retinopathy. The course of the disease was slowly progressive. All patients had maternally inherited or de novo mutations in or near exon 7 of AIFM1, within a region of 70 bp, including synonymous and intronic changes. AIFM1 mutations have previously been associated with neurologic presentations as varied as intellectual disability, hearing loss, neuropathy, and striatal necrosis, while AIFM1 mutations in this small region present with a distinct phenotype implicating bone. Analysis of cell lines derived from four patients identified significant reductions in AIFM1 mRNA and protein levels in osteoblasts. We hypothesize that AIFM1 functions in bone metabolism and myelination and is responsible for the unique phenotype in this condition

Osteogenic transdifferentiation of primary human fibroblasts to osteoblast-like cells with human platelet lysate

Inherited bone disorders account for about 10% of documented Mendelian disorders and are associated with high financial burden. Their study requires osteoblasts which play a critical role in regulating the development and maintenance of bone tissue. However, bone tissue is not always available from patients. We developed a highly efficient platelet lysate-based approach to directly transdifferentiate skin-derived human fibroblasts to osteoblast-like cells. We extensively characterized our in vitro model by examining the expression of osteoblast-specific markers during the transdifferentiation process both at the mRNA and protein level. The transdifferentiated osteoblast-like cells showed significantly increased expression of a panel of osteogenic markers. Mineral deposition and ALP activity were also shown, confirming their osteogenic properties. RNA-seq analysis allowed the global study of changes in the transcriptome of the transdifferentiated cells. The transdifferentiated cells clustered separately from the primary fibroblasts with regard to the significantly upregulated genes indicating a distinct transcriptome profile; transdifferentiated osteoblasts also showed significant enrichment in gene expression related to skeletal development and bone mineralization. Our presented in vitro model may potentially contribute to the prospect of studying osteoblast-dependent disorders in patient-derived cells