Chronic kidney disease, the presence of structural and functional abnormalities in the kidneys, is associated with a lower quality of life and increased morbidity and mortality in children. Genetic etiologies account for a substantial proportion of pediatric chronic kidney disease. With recent advances in genetic testing techniques, an increasing number of genetic causes of kidney disease continue to be found. Genetic testing is recommended in children with steroid-resistant nephrotic syndrome, congenital malformations of the kidney and urinary tract, cystic disease, or kidney disease with extrarenal manifestations. Diagnostic yields differ according to the category of clinical diagnosis and the choice of test. Here, we review the characteristics of genetic testing modalities and the implications of genetic testing in clinical genetic diagnostics.

Chronic kidney disease, the presence of structural and functional abnormalities in the kidneys, is associated with a lower quality of life and increased morbidity and mortality in children. Genetic etiologies account for a substantial proportion of pediatric chronic kidney disease. With recent advances in genetic testing techniques, an increasing number of genetic causes of kidney disease continue to be found. Genetic testing is recommended in children with steroid-resistant nephrotic syndrome, congenital malformations of the kidney and urinary tract, cystic disease, or kidney disease with extrarenal manifestations. Diagnostic yields differ according to the category of clinical diagnosis and the choice of test. Here, we review the characteristics of genetic testing modalities and the implications of genetic testing in clinical genetic diagnostics.

PURPOSE: This study was performed to investigate the etiology, clinical features, and outcomes of patients with gonadotropin-independent precocious puberty (GIPP). METHODS: The study included 16 patients (14 female and 2 male patients) who manifested secondary sexual characteristics, elevated sex hormones, or adrenal androgens with prepubertal luteinizing hormone levels after gonadotropin releasing hormone stimulation diagnosed between May 1994 and December 2015. Patients with congenital adrenal hyperplasia were excluded. Clinical features, laboratory findings, treatment modalities, and outcomes were retrospectively reviewed. RESULTS: The median age at diagnosis was 2.6 years (range, 0.7–7.9 years) and median follow-up duration was 4.6 years (range, 1 month–9.8 years). Patients with McCune-Albright syndrome (n=5) and functional ovarian cysts (n=4) presented with vaginal bleeding and elevated estradiol levels (23.3±17.5 pg/mL); adrenocortical tumors (n=4) with premature pubarche and elevated dehydroepiandrosterone sulfate levels (87.2–6,530 µg/dL); and human chorionic gonadotropin (hCG)-producing tumor (n=1) with premature pubarche and elevated β-human chorionic gonadotropin levels (47.4 mIU/mL). Two patients were idiopathic. Six patients transited to gonadotropin-dependent precocious puberty median 3.3 years (range, 0.3–5.1 years) after the onset of GIPP. Initial and follow-up height standard deviation scores (0.99±0.84 vs. 1.10±1.10, P=0.44) and bone age advancement (1.49±1.77 years vs. 2.02±1.95 years, P=0.06) were not significantly different. CONCLUSION: The etiologies of GIPP are heterogeneous, and treatment and prognosis is quite different according to the etiology. Efficacy of treatment with aromatase inhibitors needs to be evaluated after long-term follow-up.
Adrenal Hyperplasia, Congenital ; Androgens ; Aromatase Inhibitors ; Child* ; Chorionic Gonadotropin ; Dehydroepiandrosterone Sulfate ; Diagnosis ; Estradiol ; Female ; Fibrous Dysplasia, Polyostotic ; Follow-Up Studies ; Gonadal Steroid Hormones ; Gonadotropin-Releasing Hormone ; Humans ; Luteinizing Hormone ; Male ; Ovarian Cysts ; Prognosis ; Puberty, Precocious* ; Retrospective Studies ; Treatment Outcome ; Uterine Hemorrhage

PURPOSE: This study was performed to investigate the etiology, clinical features, and outcomes of patients with gonadotropin-independent precocious puberty (GIPP). METHODS: The study included 16 patients (14 female and 2 male patients) who manifested secondary sexual characteristics, elevated sex hormones, or adrenal androgens with prepubertal luteinizing hormone levels after gonadotropin releasing hormone stimulation diagnosed between May 1994 and December 2015. Patients with congenital adrenal hyperplasia were excluded. Clinical features, laboratory findings, treatment modalities, and outcomes were retrospectively reviewed. RESULTS: The median age at diagnosis was 2.6 years (range, 0.7–7.9 years) and median follow-up duration was 4.6 years (range, 1 month–9.8 years). Patients with McCune-Albright syndrome (n=5) and functional ovarian cysts (n=4) presented with vaginal bleeding and elevated estradiol levels (23.3±17.5 pg/mL); adrenocortical tumors (n=4) with premature pubarche and elevated dehydroepiandrosterone sulfate levels (87.2–6,530 µg/dL); and human chorionic gonadotropin (hCG)-producing tumor (n=1) with premature pubarche and elevated β-human chorionic gonadotropin levels (47.4 mIU/mL). Two patients were idiopathic. Six patients transited to gonadotropin-dependent precocious puberty median 3.3 years (range, 0.3–5.1 years) after the onset of GIPP. Initial and follow-up height standard deviation scores (0.99±0.84 vs. 1.10±1.10, P=0.44) and bone age advancement (1.49±1.77 years vs. 2.02±1.95 years, P=0.06) were not significantly different. CONCLUSION: The etiologies of GIPP are heterogeneous, and treatment and prognosis is quite different according to the etiology. Efficacy of treatment with aromatase inhibitors needs to be evaluated after long-term follow-up.
Adrenal Hyperplasia, Congenital ; Androgens ; Aromatase Inhibitors ; Child* ; Chorionic Gonadotropin ; Dehydroepiandrosterone Sulfate ; Diagnosis ; Estradiol ; Female ; Fibrous Dysplasia, Polyostotic ; Follow-Up Studies ; Gonadal Steroid Hormones ; Gonadotropin-Releasing Hormone ; Humans ; Luteinizing Hormone ; Male ; Ovarian Cysts ; Prognosis ; Puberty, Precocious* ; Retrospective Studies ; Treatment Outcome ; Uterine Hemorrhage

Background: Triptorelin depot is largely used to treat central precocious puberty (CPP) in children, and a 3-month depot has been introduced. However, data about the 3-month gonadotropin-releasing hormone use for treatment of CPP in Korean girls are not available.This study was conducted to compare the efficacy of a triptorelin 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of CPP. Methods: A retrospective study, including 106 girls with CPP treated with triptorelin, was conducted. Fifty patients were treated with a triptorelin 3-month depot, and 56 were treated with a triptorelin 1-month depot. Serum luteinizing hormone (LH), follicle-stimulating hormone, and estradiol levels were analysed every 6 months after the visit. The height and bone age of each patient was evaluated at the beginning of treatment, after 6 months, and one year after therapy. Results: The baseline characteristics of the girls treated with a 3-month depot were similar to those of the girls treated with a 1-month depot. A suppressed levels of LH to the triptorelin injection (serum LH < 2.5 IU/L) at 6 months was seen in 90.0% and 98.2% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.160). After 1 year of treatment, a suppressed levels of LH was seen in 93.5% and 100% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.226). Height velocity showed no significant difference between the two groups. Degree of bone age advancement decreased from 1.22 ± 0.07 and 1.22 ± 0.08 years at baseline (P = 0.914) to 1.16 ± 0.07 and 1.17 ± 0.08 in the girls treated with the 3-month and 1-month depots after 1 year, respectively (P = 0.481). Conclusion This study showed that the efficacy of long-acting triptorelin 3-month was comparable to 1-month depot regarding hormonal suppression and inhibition of bone maturation. The triptorelin 11.25 mg 3-month depot is an effective treatment for girls with CPP.

Background: Triptorelin depot is largely used to treat central precocious puberty (CPP) in children, and a 3-month depot has been introduced. However, data about the 3-month gonadotropin-releasing hormone use for treatment of CPP in Korean girls are not available.This study was conducted to compare the efficacy of a triptorelin 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of CPP. Methods: A retrospective study, including 106 girls with CPP treated with triptorelin, was conducted. Fifty patients were treated with a triptorelin 3-month depot, and 56 were treated with a triptorelin 1-month depot. Serum luteinizing hormone (LH), follicle-stimulating hormone, and estradiol levels were analysed every 6 months after the visit. The height and bone age of each patient was evaluated at the beginning of treatment, after 6 months, and one year after therapy. Results: The baseline characteristics of the girls treated with a 3-month depot were similar to those of the girls treated with a 1-month depot. A suppressed levels of LH to the triptorelin injection (serum LH < 2.5 IU/L) at 6 months was seen in 90.0% and 98.2% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.160). After 1 year of treatment, a suppressed levels of LH was seen in 93.5% and 100% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.226). Height velocity showed no significant difference between the two groups. Degree of bone age advancement decreased from 1.22 ± 0.07 and 1.22 ± 0.08 years at baseline (P = 0.914) to 1.16 ± 0.07 and 1.17 ± 0.08 in the girls treated with the 3-month and 1-month depots after 1 year, respectively (P = 0.481). Conclusion This study showed that the efficacy of long-acting triptorelin 3-month was comparable to 1-month depot regarding hormonal suppression and inhibition of bone maturation. The triptorelin 11.25 mg 3-month depot is an effective treatment for girls with CPP.

Purpose: Idiopathic scoliosis is the most common form of scoliosis, and the risk of onset and progression has been found to correlate with growth spurts. Therefore, treatment with recombinant human growth hormone (GH) treatment in short children may initiate and/or aggravate scoliosis. The aim of this study was to investigate the relationship between idiopathic scoliosis and GH treatment in short children. Methods: The medical records of 113 subjects seen at the participating institution between January 2010 and December 2020 and who were diagnosed with GH deficiency and small for gestational age, had idiopathic short stature, and were treated with GH for at least one year were reviewed. Scoliosis was defined as a Cobb angle greater than 10 degrees as assessed using a spine x-ray. Clinical data and laboratory findings before and 12 months after GH treatment were compared. Results: There was significant increase in height, height-standard deviation score, insulin-like growth factor 1, and insulin-like growth factor binding protein 3 (p<0.001) with GH treatment. However, there were no significant differences in the average Cobb angle (6.2°±3.3° vs. 6.1°±3.5°, p=0.842) and the prevalence of scoliosis (9.7% vs. 13.3%, p=0.481) before and after one year of GH treatment. A comparative analysis of both initial Cobb angle and change in Cobb angle during GH treatment showed no relationship with other factors. Conclusion Although GH treatment in short children increased height and growth velocity, it was not associated with development or aggravation of idiopathic scoliosis.

Purpose: The prevalence of adolescents with type 2 diabetes mellitus (T2DM) has rapidly increased in Korea over the past few decades with the increase in the number of obese adolescents. The single point insulin sensitivity estimator (SPISE) was recently introduced as a surrogate marker for insulin sensitivity to predict T2DM in adults. We aimed to determine risk factors for T2DM in obese adolescents, including SPISE. Methods: This retrospective study included 104 adolescents diagnosed with T2DM at Korea University Hospital between January 2010 and December 2020. We compared clinical and biochemical parameters and the SPISE of normoglycemic overweight and obese individuals with those of prediabetic and diabetic adolescents to determine risk factors for T2DM. Receiver operating characteristic analysis was performed with the Youden index to determine the cutoff point of SPISE. Results: Frequency of fatty liver and family history of T2DM were significantly higher and SPISE level was significantly lower in patients with T2DM than in normoglycemic overweight/obese and prediabetic adolescents (p<0.01). A family history of T2DM, fatty liver, and SPISE value below the cutoff point (4.49) were identified as significant risk factors for T2DM in multiple logistic regression analysis after controlling for age, sex, and body mass index standard deviation score (p<0.01). Conclusion Family history of T2DM, fatty liver, and low SPISE (<4.49) are risk factors that can independently affect the occurrence of T2DM in obese adolescents. Among these risk factors, SPISE is a promising marker for predicting adolescent T2DM; careful monitoring of these individuals is needed to prevent progression to T2DM.

Purpose: The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). Gonadorelin (Relefact) is used for the test but is not always readily available; triptorelin is used as an alternative. The purpose of this study was to evaluate the diagnostic validity of the triptorelin test compared with the GnRH test in the diagnosis of CPP in girls. Methods: This retrospective study included 100 girls with premature thelarche (PT) who underwent a hypothalamic-pituitary-gonadal axis evaluation. In the overall group, 50 girls were tested with intravenous gonadorelin (Relefact) and 50 girls were tested with subcutaneous triptorelin acetate (Decapeptyl). Luteinizing hormone (LH) and follicle-stimulating hormone levels were measured at baseline and 30, 45, 60, and 90 minutes after gonadorelin injection or 30, 60, 90, and 120 minutes after triptorelin injection. Results: Clinical characteristics of age, height, weight, body mass index, and bone age were similar between the 2 groups. The highest LH level was reached 60 minutes after stimulation in both groups. Approximately 20% of the gonadorelin group and 24% of the triptorelin group were diagnosed with CPP (P=0.52). Among those diagnosed with CPP, the mean peak LH concentrations were 8.15 mIU/mL and 9.73 mIU/mL in the gonadorelin and triptorelin groups, respectively. Conclusion The triptorelin test showed similar trends of LH elevation and diagnostic rate compared with the traditional GnRH test for diagnosing CPP. This suggests that the triptorelin test may be a valid alternative to the GnRH test for differentiating CPP from self-limiting PT. Our study also demonstrated that a triptorelin stimulation test for up to 120 minutes was sufficient to diagnose CPP.

Turner syndrome is one of the most common chromosomal disorders. It is caused by numerical or structural abnormalities of the X chromosome and results in short stature and gonadal dysgenesis. The short stature arises from haploinsufficiency of the SHOX gene, whereas overdosage contributes to tall stature. This report describes the first Korean case of Turner syndrome with tall stature caused by SHOX overdosage. The patient presented with primary amenorrhea and hypergonadotropic hypogonadism at the age of 17 years. Estrogen replacement therapy was initiated at that time. She displayed tall stature from childhood, with normal growth velocity, and reached a final height of 190 cm (standard deviation score, 4.3) at the age of 30 years. Her karyotype was 46,X, psu idic(X)(q21.2), representing partial monosomy of Xq and partial trisomy of Xp. Analysis by multiplex ligation-dependent probe amplification detected a duplication at Xp22.3-Xp22.2, encompassing the PPP2R3 gene near the 5'-end of the SHOX gene through the FANCD gene at Xp22.2.
Amenorrhea ; Chromosome Deletion ; Chromosome Disorders ; Estrogen Replacement Therapy ; Female ; Gonadal Dysgenesis ; Haploinsufficiency ; Humans ; Hypogonadism ; Karyotype ; Multiplex Polymerase Chain Reaction ; Trisomy ; Turner Syndrome* ; X Chromosome