Comprehensive analysis of chemokine gene polymorphisms in Korean children with autoimmune thyroid disease.

Chemokines are chemotactic cytokines that can cause directed migration of leukocytes. The aim of this study was to examine differences in single nucleotide polymorphisms (SNP) of chemokine in AITD patients compared to normal controls. A total of 86 Korean pediatric patients were included in the patient group and 183 adults were included in the normal control group. To compare influences of several chemokine gene polymorphisms, 25 SNPs in 16 chemokine genes were analyzed. Genotype frequencies of CCL11(rs3744508)AA(OR = 6.9) and CCR2(rs1799864)AA(OR = 3.8) were higher in the AITD patients than in the controls, whereas CCL17(rs223828)CC was lower in the AITD patients than in the controls(OR = 0.4). In comparison between Graves' disease (GD) patients and controls, genotype frequency of CCL17(rs223828)CC(OR = 0.4) was lower in the GD group, whereas those of CCR2(rs1799864)AA(OR = 4.8) were higher in the GD group. The genotype frequency of CCL11(rs3744508)AA(OR = 11.3) was higher in Hashimoto's thyroiditis (HT) patients, whereas that of CXCL8(rs2227306)CC(OR = 0.4) was lower in HT patients. Polymorphisms of CCL11(rs3744508), CCL17(rs223828), and CCR2(rs1799864) might be associated with AITD, with CCL17(rs223828), CCR2(rs1799864) and CXCR2(rs2230054, rs1126579) affecting GD and CCL11(rs3744508) and CXCL8(rs2227306) affecting HT in Korean children.

A Case of X-Linked Adrenal Hypoplasia Congenital (AHC) Due to Large Deletion of NR0B1 (DAX1) and Contiguous Gene.

X-linked adrenal hypoplasia congenita (AHC) is caused predominantly by mutations in the NR0B1 (DAX1) gene. Among these, X-linked AHC due to a large deletion of NR0B1 is extremely rare. In Korea, the first case was reported in 2005, and there have been no further documented cases since then. Herein, we report a unique case of X-linked AHC caused by an entire gene deletion that includes the NR0B1 gene and seven other genes. A seven-day-old boy presented to a pediatric endocrine clinic with prolonged postnatal jaundice, skin hyperpigmentation, hyponatremia, and hyperkalemia, suggestive of an adrenal crisis. In genetic analysis, next-generation sequencing panel for congenital adrenal hyperplasia (CAH) showed no variants. However, chromosomal microarray results revealed large deletion of Xp21.2 (29,655,007_30,765,126) including eight protein-coding genes (NR0B1, IL1RAPL1, GK, MAGEB1-4, TASL). In cases of atypical adrenal insufficiency and genetically undiagnosed CAH, NR0B1-related AHC should be suspected, as Xp21 deletion is very rare and not detected in NGS, making microarray the best option for genetic diagnosis.

Short-term effect of growth hormone treatment in childhood leukemia survivors with growth hormone deficiency.

PURPOSE: Survivors of childhood leukemia are at risk of growth impairment due to intensive chemotherapy and radiation treatments. This study investigated the auxological and biochemical characteristics of childhood leukemia survivors diagnosed with growth hormone deficiency (GHD) and the changes in these parameters after 1 year of growth hormone (GH) treatment. METHODS: A total of 24 children diagnosed with GHD after leukemia treatment was analyzed. Clinical and biochemical data were collected retrospectively at leukemia diagnosis, GHD diagnosis, and 1 year after GH treatment. Standard deviation score (SDS) was calculated based on the age- and gender-adjusted population. RESULTS: Of the 24 children included in this study, 19 received GH treatment. The median age at GHD diagnosis was 12.3 years, and the median delay in bone age was 1.46 years. Height SDS decreased from -0.69 at leukemia diagnosis to -2.58 at GHD diagnosis (P<0.001). The change in height SDS with and without GH for 1 year was 0.35 and -0.21, respectively (P=0.044). In regression analyses, higher height SDS at GHD diagnosis and a smaller decrease of the height SDS between leukemia and GHD diagnoses were positively correlated with height SDS after GH treatment. CONCLUSION: GH treatment could be beneficial and safe for improving height in childhood leukemia survivors with GHD. Height SDS at GHD diagnosis and reduction of height SDS between leukemia and GHD diagnosis could be potential factors in predicting the therapeutic effects. Close auxological monitoring is recommended for any childhood leukemia survivors who experience posttreatment height decline.

Factors affecting bone mineral density in children and adolescents with secondary osteoporosis.

PURPOSE: This study aimed to investigate the clinical factors associated with bone mineral density (BMD) among children and adolescents with osteoporosis secondary to treatment for underlying clinical conditions. METHODS: We retrospectively reviewed the medical records of patients aged 10-18 years and evaluated them for lumbar spine BMD (LSBMD) after treatment for underlying diseases, including hemato-oncologic, rheumatologic system, and inflammator y bowel diseases. LSBMD measured by dual-energy x-ray absorptiometry (DXA) performed from March 2019 to March 2021 was evaluated. We analyzed 117 patients who underwent initial DXA after treatment for underlying diseases. RESULTS: Subjects in this study had multiple underlying diseases: hemato-oncologic (78.6%), rheumatologic (11.1%), and inflammatory bowel diseases (10.3%). There was no significant association between the z-score and bone metabolic markers (P>0.05). However, higher cumulative glucocorticoid (GC) dose significantly reduced LSBMD z-score (P=0.029). Moreover, the association between cumulative dose of GC and initial z-score of LSBMD was significant in logarithmic regression analysis (P=0.003, R2=0.149). GC accumulation was a significant risk factor for vertebral fracture when the initial BMD was evaluated after treatment (P=0.043). Bone metabolic markers did not significantly influence the risk of vertebral fracture. CONCLUSION: Initial bone mass density of the lumbar spine evaluated after long-term GC use for underlying diseases is a predictor of further vertebral fractures.

Exon sequencing of the alpha-2-globin gene for the differential diagnosis of central cyanosis in newborns: a case report.

BACKGROUND: Cyanosis is usually associated with serious conditions requiring urgent treatment in the neonatal intensive care unit (NICU). Hemoglobin M (Hb M) disease is one type of congenital methemoglobinemia characterized by cyanosis. Among these variants, α-globin chain mutations such as Hb M Boston present cyanosis from birth while other variants usually manifest later in life. CASE PRESENTATION: We report a case of a male newborn with cyanosis apparent since birth. Surprisingly, his respiratory and hemodynamic status including normal arterial blood oxygen saturation was stable, but oxygen saturation on pulse oximetry did not increase after 100% supplemental oxygen was started. In addition to routine pulmonary and cardiologic evaluation, further evaluation for dyshemoglobin was conducted; α2-globin gene sequencing showed a single-point variant causing Hb M Boston. Methemoglobin (MetHb) level estimated by co-oximetry was normal. After a 14-day stay in the NICU, the patient remained respiratory and hemodynamically stable without supplemental oxygen except for cyanosis. CONCLUSIONS: Hb M disease is a benign disease and does not require any treatment whereas acquired methemoglobinemia is a potentially fatal condition. Neonatologists should be aware that low oxygenation status on pulse oximetry in the face of normal arterial blood saturation values might indicate the possibility of Hb M disease in early neonatal cyanosis, irrespective of MetHb value.