Mutations in the IARS1 gene are rare in clinical practice， and up to now， only ten cases with detailed clinical and genetic data have been recorded in the literature. This article reports a case of growth retardation， intellectual developmental disorder， hypotonia， and hepatopathy （GRIDHH） associated with single heterozygous mutations in the IARS1 gene and summarizes the clinical and genetic features of GRIDHH， thereby expanding the genetic spectrum of GRIDHH.

Clinical data of a child with SIM1 gene mutation-related obesity who visited Beijing Children′s Hospital, Capital Medical University in February 2022 was retrospectively analyzed.This 5-year-and-4-month-old girl was admitted for early onset obesity.She showed obesity at 29 months old, accompanied by severe obstructive sleep apnea syndrome.The patient and her mother had heterozygous variations in the SIM1 gene.Literature has reported a total of 42 patients with obesity caused by SIM1 gene mutations from different families in the world, and nearly 1/3 of patients had clinical manifestations beyond obesity, such as developmental delay, cognitive and behavioral problems, mild dysmorphic appearance, and neuroendocrine abnormalities.The patient in this study was mainly characterized by early onset obesity.At present, 58 SIM1 gene mutations are found to be related to obesity, which are mostly concentrated in the C-terminal domain.The allele frequency of p. T46R and p. D707H has reached 9.5%; therefore, p.T46R and p. D707H are considered hot spot variations, suggesting that SIM1 gene analysis should be improved for patients with early onset obesity.

Objective:To analyze the genetic and clinical characteristics, treatment and prognosis of patients diagnosed with maturity onset of diabetes of the young (MODY) 12 subtype.Methods:This retrospective study collected and analyzed data from 5 children with MODY12 subtype caused by ABCC8 gene variants who underwent inpatient and outpatient genetic testing at Beijing Children′s Hospital from January 2016 to December 2023. Their clinical and genetic features, treatment, and follow-up results were analyzed.Results:Among the 5 patients with MODY12 subtype, 4 were male and 1 was female, with an age of 13.4 (5.5, 14.6) years. Four of the patients were born large for gestational age, while one was born small for gestational age. Two patients were overweight or obese. Three patients exhibited typical symptoms of diabetes, while 2 were incidentally found to have elevated blood glucose level. One patient was found to have diabetic ketoacidosis at onset, who was diagnosed with congenital hyperinsulinism during the neonatal period and received diazoxide treatment, and experienced intellectual developmental delay. All 5 patients had autosomal dominant inherited diabetes within 3 generations. The fasting blood glucose at onset was 7.5 (6.5, 10.0) mmol/L, the haemoglobin A1c (HbA1c) was 11.8% (7.5%, 13.5%), and the fasting C-peptide was 1.2 (1.1, 2.2) μg/L. The duration of follow-up was 15 (9, 32) months. One patient underwent lifestyle intervention, 2 received metformin orally, 1 received insulin therapy, and the other received subcutaneous injection of insulin combined with sulfonylurea orally. At the last follow-up, the median fasting blood glucose was 6.1 (5.1, 7.0) mmol/L, the HbA1c was 5.9% (5.7%, 7.1%), and the fasting C-peptide was 1.7 (0.9, 2.9) μg/L. One patient developed diabetic retinopathy. There were 4 missense variations in ABCC8 gene and one in-frame deletion, all of which were maternally inherited heterozygotes.Conclusions:MODY12 subtype is a heterogeneous disorder with the age of onset from infancy to adolescence. It can present as mild hyperglycemia or diabetic ketoacidosis, and has a high incidence of obesity. Definitive diagnosis can be achieved through genetic test, and individualized treatment is recommended based on glucose levels.

Objective:To evaluate the effectiveness and safety of treatment with Burosumab in pediatric X-linked hypophosphatemia (XLH) patients.Methods:In this retrospective case study, 4 children with pediatric XLH, who were treated with Burosumab in Beijing Children′s Hospital, Capital Medical University and Shandong Provincial Hospital affiliated to Shandong First Medical University from July 2022 to December 2023, were selected as the study objects. We collected and analyzed their clinical characteristics, biochemical indicators, imaging results, and treatment. The children were followed up every 3 months until December 2023, and the clinical outcomes and adverse drug reactions after treatment were evaluated.Results:Of the 4 patients, 3 were males and 1 was female; they were aged 6.7, 2.9, 2.1, and 2.3 years, respectively. Three patients had previously received treatment with phosphate supplements and active vitamins, but their wadding gait and lower limb deformities did not improve significantly, neither did their imaging changes of active richets. The initial dose of Burosumab in the 4 patients was 0.8 mg/kg, administered subcutaneously every 2 weeks, with a treatment course of 0.8-1.3 years. The fasting serum phosphorus and tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) of the 4 patients before treatment were 0.72, 0.95, 0.81, 0.66 mmol/L and 0.67, 0.85, 0.87, 0.61 mmol/L, respectively. At the last follow-up, the fasting serum phosphorus and TmP/GFR levels were significantly increased (0.96, 1.09, 1.09, 0.90 mmol/L, and 0.85, 0.79, 1.03, 0.98 mmol/L, respectively). Among them, only the TmP/GFR level (1.17 mmol/L) in case 2 achieved normal values at 3 months post-therapy, while the rest did not reach the normal range for children of the same age. After treatment, the alkaline phosphatase levels of all patients gradually decreased (the values were 461, 240, 423, and 237 U/L, respectively), and the ALP levels in cases 2 and 4 returned to normal at the last visit. Case 4 showed a slight increase in parathyroid hormone (PTH) levels after 9 months of treatment, while the PTH levels in the rest 3 cases remained normal. Case 1 underwent a 6-minute walking test, and the walking distance increased from 245 m to 570 m. Abnormal gait, lower limb deformity, and the severity of rickets in the 4 patients had all improved. No adverse drug reactions such as nephrocalcinosis, local skin injection reaction, hyperphosphatemia, or vitamin D deficiency were observed.Conclusion:Burosumab can improve clinical symptoms in children with XLH with a good safety profile.

Objective:To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS).Methods:A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children′s Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results:The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses ( t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions:Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

Graves′ disease (GD) is the most prevalent cause of hyperthyroidism in children, posing a significant threat to their normal growth and development.The incidence of GD is increasing year by year.Antithyroid drugs are the preferred treatment for GD in children, which can alleviate immune disorders and normalize thyroid function in a short period of time.However, there are still numerous unsolved problems and controversies surrounding this treatment, and the challenges that need to be overcome include the low remission rate, high recurrence rate and high incidence of adverse reactions.The key challenges facing antithyroid drug therapy are how to normalize thyroid function quickly, maintain therapeutic efficacy and reduce recurrence rate, and further studies are needed to improve the effectiveness and safety of the therapy.This article summarizes and reviews the therapeutic strategies, controversies and adverse reactions of antithyroid drugs for GD in children and adolescents.

Humans ; Child, Preschool ; Insulin/therapeutic use* ; Diabetes Mellitus, Type 1/drug therapy* ; Retrospective Studies ; Hypoglycemic Agents/therapeutic use* ; Diabetes Mellitus, Type 2 ; Blood Glucose

The developments of mass spectrometry and gene detection technology and the introduction of newborn screening have led to an expanding population of patients with inherited metabolic diseases.Therapies of inherited metabolic diseases have attracted much attention.The basic principles of management in these diseases are to limite the consumption of nutrients that produce toxic products, supplement deficient substances, and increase excretion of toxic metabolites.Dietary therapy is one of the major treatments for many inherited metabolic disorders, with the starting point of limiting the intake of substrates for metabolic disorders and supplementing products of insufficient synthesis or alternative energy sources to bypass the defective pathway in order to maintain normal growth and development.With more and more special medical formula nutritional foods being put into production and use, dietary therapy become accessible and compliant.With the effective dietary therapy, many patients get clinical symptom controlled, and their quality of life has been improved.This article mainly elaborates the common inherited metabolic diseases dietary therapy.

Humans ; Hypogonadism/drug therapy* ; Male ; Puberty ; Puberty, Delayed ; Treatment Outcome

Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental retardation disease involving multiple organ and system abnormalities.The main manifestations include broad thumbs and big toes, specific facial characteristics, developmental and mental retardation.In addition, it is also manifested as ocular abnormalities, hearing loss, repeated respiratory infection and dyspnea, gastrointestinal disorders, urogenital system disorders and severe constipation.It can be classified into 2 types: RSTS1 (OMIM#180849) caused by the CREBBP gene mutation and RSTS2 (OMIM#613684) caused by the EP300 gene mutation, and most of them are found in the de novo truncated variation.Up to now, a clear diagnosis criterion for RSTS is lacked, which is mainly based on the comprehensive analysis of clinical and genetic results.The main treatment of RSTS is symptomatic and individualized treatment, while early intervention is helpful to improve the prognosis and the quality of life.This study aims to introduce the disease comprehensively, thus enhancing the recognition in RSTS.