RESUMO
The clinical presentation, treatment, and follow-up of two boys with type 1 Dent disease who exhibited a Bartter-like phenotype were retropectively analysed. The related literature of pediatric patients with type 1 Dent disease who had hypokalemia and metabolic alkalosis was screened through databases such as PubMed, CNKI, and Wanfang until February 1, 2024, and common features among these patients were summarized through literature review. A total of 7 literatures were included, and 9 children were included in the analysis. All patients were male, presenting with significant low molecular weight proteinuria and hypercalciuria. Other prominent characteristic phenotypes included short stature (7/8), hypophosphatemia (8/9), and rickets (6/8). Seven previously reported patients had missense or nonsense mutations, while 2 patients in this study carried possible pathogenic mutations in the CLCN5 gene, c.315+2T>A (p.?) and c.584dupT (p.I196Yfs*6), respectively. Five patients were able to maintain blood potassium levels around 3 mmol/L with oral potassium chloride solution combined with non-steroidal anti-inflammatory drugs (ibuprofen or indomethacin). The follow-up showed that 2 patients developed chronic kidney disease stage 4 and stage 3 at the age of 13 and 21 years, respectively. The phenotypic overlap between Dent disease and Batter syndrome is considerable,with the distinguishing feature being the presence of significant low molecular weight proteinuria. Patients with type 1 Dent disease presenting with the Bartter-like phenotype have a high prevalence of short stature, hypophosphatemia, and rickets. Non-steroidal anti-inflammatory drugs can be used to correct hypokalemia in patients under periodic renal function assessment.
Assuntos
Fenótipo , Humanos , Masculino , Criança , Hipopotassemia , Mutação , Doença de Dent/genética , Doença de Dent/diagnóstico , Canais de Cloreto/genética , Hipofosfatemia , Síndrome de Bartter/genética , Síndrome de Bartter/diagnóstico , Hipercalciúria , Raquitismo/diagnóstico , Proteinúria , Doenças Genéticas Ligadas ao Cromossomo X , NefrolitíaseRESUMO
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.
Assuntos
Anticorpos Monoclonais Humanizados , Raquitismo Hipofosfatêmico Familiar , Humanos , Masculino , Feminino , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Criança , Estudos Retrospectivos , Pré-Escolar , Resultado do TratamentoRESUMO
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=4.05ã3.56ã2.55ã2.23 and 3.88ã3.50ã2.50ã2.19, 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.
Assuntos
Síndrome de Resistência a Andrógenos , Pênis , Testosterona , Humanos , Masculino , Criança , Testosterona/análogos & derivados , Testosterona/administração & dosagem , Testosterona/uso terapêutico , Feminino , Administração Oral , Resultado do Tratamento , Síndrome de Resistência a Andrógenos/tratamento farmacológico , Adolescente , Pré-Escolar , Pênis/anormalidades , Pênis/efeitos dos fármacos , Androgênios/administração & dosagem , Androgênios/uso terapêutico , LactenteRESUMO
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.
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Diabetes Mellitus Tipo 2 , Receptores de Sulfonilureias , Humanos , Feminino , Masculino , Estudos Retrospectivos , Criança , Adolescente , Prognóstico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/diagnóstico , Receptores de Sulfonilureias/genética , Glicemia/análise , Pré-Escolar , Hipoglicemiantes/uso terapêutico , Mutação , Hemoglobinas Glicadas/análise , Insulina/uso terapêuticoRESUMO
Objective: To analyse the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) with syndormic and non-syndormic short stature. Methods: The clinical data of 59 children born SGA who were diagnosed as short stature and admitted to the Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital from July 2012 to June 2021 were collected and analyzed. According to the 2019 consensus on short stature, they were divided into syndromic group and non-syndromic group. Before treatment and 6, 12, 18 and 24 months after treatment, height standard deviation score (Ht-SDS), difference of height standard deviation (∆Ht-SDS) and homeostasis model assessment-insulin resistance index (HOMA-IR) were compared between groups, while Ht-SDS and HOMA-IR were compared before and after treatment. Independent t test or Kruskal-Wallis test were used for comparison between the 2 groups, and paired t test or Mann-Whitney U test were used for the intra-group comparison. Results: Among the 59 cases, 37 were males and 22 females, aged (5.5±2.3) years. There was no significant difference in Ht-SDS after 12 months of treatment between 2 groups (0.9±0.4 vs. 1.2±0.4, t=1.68, P=0.104) or in height SDS after 24 months of treatment (1.4±0.7 vs. 1.9±0.5, t=1.52, P=0.151). After 12 months of treatment, the insulin resistance index of the non-syndromic group was significantly higher than that of the syndromic group (2.29 (1.43, 2.99) vs. 0.90 (0.55, 1.40), Z=-2.95, P=0.003). There were significant differences in Ht-SDS between 6 months and before treatment, 12 months and 6 months in syndromic type (Z=7.65, 2.83 P<0.001, P=0.020), but all were significant differences in non-syndromic type between 6 months and before treatment, 12 months and 6 months, 18 months and 12 months, 24 months and 18 months (Z=11.95, 7.54, 4.26, 3.83, all P<0.001). Conclusion: The efficacy of rhGH treatment in children born SGA is comparable between syndromic and non-syndromic short stature cases, but non-syndromic children treated with rhGH need more frequent follow-up due to the risk of insulin resistance.
Assuntos
Hormônio do Crescimento Humano , Resistência à Insulina , Criança , Feminino , Humanos , Masculino , Estatura , Idade Gestacional , Hormônio do Crescimento Humano/uso terapêutico , Recém-Nascido Pequeno para a Idade Gestacional , Insulina , Proteínas Recombinantes , Pré-EscolarRESUMO
Objective: To evaluate the consistency of mass spectrometry (MS) and chemiluminescence immunoassay (CLIA) in detecting serum insulin-like growth factor-1 (IGF-1) and IGF-1 standard deviation score (SDS). Methods: This cross-sectional parallel control study prospectively collected the serum samples of 115 children with short stature disorders who were admitted in the Department of Endocrinology, Beijing Children's Hospital, Capital Medical University from February 2020 to December 2021. The serum IGF-1 level was detected by CLIA and MS, and converted to SDS for consistency analysis. Pearson analysis was used to analyze the correlation between the 2 methods, and Deming regression equation was established. Bland-Altman diagram and weighted Kappa coefficient were used to evaluate the consistency of the 2 methods. Results: There were 46 boys (40.0%) and 69 girls (60.0%), aged (8±3) years. Among the 115 cases, 37 were Turner syndrome, 59 were small for gestational age (SGA) at term, 1 was growth hormone deficiency (GHD) and 18 were other diseases. Pearson correlation analysis showed a preferable correlation between IGF-1 measured by the 2 detection methods (r=0.94, P<0.01), and IGF-1 SDS was also significantly correlated (r=0.92, P<0.01). Bland-Altman analysis showed that the consistency of serum IGF-1 levels detected by the 2 methods was poor, and the mean difference between CLIA and MS was 33.38 µg/L. The result detected by CLIA was significantly higher than that by MS, with SDS of 43.51 µg/L (95%CI -51.89-118.7 µg/L). After converting the results to SDS and removing 3 outliers (including 1 GHD patient), the weighted Kappa showed acceptable consistency (κ=0.68). Conclusion: In clinical application, after converting to IGF-1 SDS, IGF-1 detected by MS and CLIA can be used for cross-reference, but too high or too low levels should be cautious about.
Assuntos
Hormônio do Crescimento Humano , Insulinas , Estatura , Criança , Estudos Transversais , Feminino , Transtornos do Crescimento/diagnóstico , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , MasculinoRESUMO
Objective: To analyze the trends of overweight and obesity prevalence in Chinese children, aged from 6 to 15 years old among 4 provinces and cities from 2009 to 2019. Methods: Reviewed the national multi-center epidemiological survey data of children from the National Key Technology R&D Program of China during the Eleventh Five-Year Plan (2009 to 2010) and the National Key Research and Development Program of China during the Thirteenth Five-Year Plan (2017 to 2019). The participants' data were selected from four provinces,municipalities and autonomous region,including Beijing, Tianjin (Northern region), Zhejiang (Eastern region), and Guangxi (Southern region). Totally 14 597 pairs of 6-15 year-old children were surveyed. According to the body mass index (BMI) and standard deviation score (SDS) of children among different genders, ages, and regions, t test or chi-square test was used to evaluate the changes in overweight and obesity over a 10-year span. Results: Totally 7 721 pairs of boys and 6 876 pairs of girls were collectted in this study, whose mean age was (10.7±2.5) years. In the past 10 years, the overall BMISDS were 0.39±1.24 and 0.36±1.31 and the overall obesity rate were 11.8% (n=1 773) anel 12.5% (n=1 813) of children in the 4 administrative regions did not have statistically significant differences (all P>0.05). However, the overall overweight rate rose from 17.1% (n=2 496) to 19.1% (n=2 781) (χ²=18.657, P<0.01), and the average annual growth rate was 0.20%. The BMISDS in the Eastern region increased from 0.10±1.07 to 0.19±1.22 (t=-4.095, P<0.01), and the overweight rate and obesity rate increased by 3.8% (n=202) and 3.1% (n=169) respectively (both P<0.01); the BMISDS in the Northern region and the obesity rate did not have statistically significant differences(all P>0.05), but the overweight rate rose from 20.5% (n=1 233) to 22.8% (n=1 365) significantly (χ²=7.431, P<0.01); BMISDS in the Southern region was significantly decreased from 0.30±1.19 to 0.09±1.25 (t=1.426, P<0.01), and the rate of obesity decreased from 9.8% (n=315) to7.9% (n=256) (χ²=6.46, P<0.05), the overweight rate was not stafistically significant (P=0.10), respectively. The obesity rate of boys had risen from 16.4% (n=1 265) to 18.2% (1 407) (χ²=8.997, P<0.01) in the past 10 years, and the overweight rate had risen from 18.0% (n=1 393) to 20.5% (n=1 579) (χ²=14.26, P<0.01). The overweight+obesity rate rose from 34.4% (n=2 658) to 38.7% (n=2 986) (χ²=29.859, P<0.01), and the weight problem in the age group of 8 to 11 years was particularly severe (all P<0.01). The obesity rate of girls dropped from 6.8% (n=468) to 5.9% (n=406) (χ²=4.546, P<0.05), the overweight rate rose from 16.0% (n=1 103) to 17.5% (n=1 202) (χ²=5.006, P<0.05), and the overall overweight+obesity rate rose from 22.8% (n=1 571) to 23.4% (n=1 608) (χ²=0.53, P>0.05). Conclusions: The growth rate of obesity among children in China had slowed down from 2009 to 2019, but the overweight rate was still on the rise. The overall base of overweight and obesity population continued to expand. The weight problem of peri-adolescent boys was particularly prominent. The current status of obesity epidemics in different regions, ages, and genders are significantly different and had their own characteristics. It is necessary to establish a personalized prevention and control strategy.
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Obesidade , Sobrepeso , Adolescente , Índice de Massa Corporal , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Sobrepeso/epidemiologia , PrevalênciaRESUMO
Objective: To investigate the clinical and genetic features, and treatment of X-linked hypophosphatemic rickets (XLH). Methods: In this retrospective study, we reviewed the medical records of 25 pediatric patients with XLH who were admitted to Department of Endocrinology Genetics and Metabolism,Beijing Children's Hospital from January 2010 to January 2020. The clinical characteristics, PHEX gene variants, as well as clinical outcome of the patients were summarized. To analyze the correlation between genotype and phenotype, the patients were divided into different subgroups according to the location of the variants, including N-terminal-located vs. C-terminal-located variant, and Zn-binding domain exon 17 or 19 variant vs. non-exon 17 or 19 variant. The age at onset, height standard deviation score (HtSDS), intercondylar or intermalleolar distance, fasting serum phosphorus, and HtSDS and intercondylar or intermalleolar distance at the final follow-up were compared by rank sum test or t text. Results: Among the 25 children with XLH, 8 were boys and 17 were girls. The median age of onset was 1.2 (1.0, 1.8) years, and the median age of diagnosis was 2.5 (1.5, 4.3) years. The main clinical manifestations were abnormal gait and lower limb deformity. The HtSDS was -2.0(-3.2, -0.8), and the intercondylar or intermalleolar distance was 4.5 (3.0, 6.0) cm. The fasting serum phosphorus level was 0.8 (0.7, 0.9) mmol/L, while the serum alkaline phosphatase level was (721±41) U/L and the serum calcium level was (2.5±0.1) mmol/L. Three patients (12%) had parathyroid hormone levels above the upper limit of the normal range. Twenty-five patients (100%) showed radiographic changes of active rickets. Nephrocalcinosis was found in 2 cases (9%). Twenty-four different PHEX variations were detected in 25 patients, among whom 11 (44%) had not been reported previously. No hot spot variation was found. No statistical differences (all P>0.05) were identified in clinical features and outcomes either in comparing patients with N-terminal (21 cases) and C-terminal (4 cases) variants, or in comparing patients with variant located in exon 17 or 19 (4 cases) or not (21 cases). Twenty-four cases (96%) were treated regularly with phosphate supplements and active vitamin D. After 2.7 (1.6, 5.0) years of follow-up, clinical symptoms were relieved in 96% (24/25) of the patients. The HtSDS after treatment had no significant difference compared to that before treatment (-2.0(-3.2, -0.8) vs.-2.0(-2.8, -1.1),Z =-0.156, P>0.05), while the intercondylar or intermalleolar distance after treatment was significantly reduced compared to that before treatment (4.5(3.0, 6.0) vs. 1.5(0, 3.3) cm, Z =-3.043, P<0.05). Bone X-rays were reexamined in 17 cases after treatment, and radiographic signs of rickets were improved. Eighteen cases had secondary hyperparathyroidism and 7 cases had nephrocalcinosis. Conclusions: The main clinical manifestations of XLH are abnormal gait, lower limb deformity and short stature. A high proportion of novel variations of PHEX gene but no hot spot variation neither genotype-phenotype correlation are found. Regular treatment with phosphate supplements and active vitamin D can significantly improve the symptoms except for the height. However, the rate of adverse events including secondary hyperparathyroidism and nephrocalcinosis seems to be high.
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Raquitismo Hipofosfatêmico Familiar , Doenças Genéticas Ligadas ao Cromossomo X , Criança , Pré-Escolar , Éxons , Raquitismo Hipofosfatêmico Familiar/genética , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Lactente , Masculino , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Fenótipo , Estudos RetrospectivosRESUMO
Objective: To explore the clinical and genetic characteristics of Noonan syndrome in children. Methods: The clinical characteristics,genetic analysis and follow-up data of 20 children diagnosed with Noonan syndrome who were admitted to Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University from March 2016 to December 2020 were retrospectively analyzed. Results: Among 20 children with Noonan syndrome, 13 were males and 7 were females. The age at diagnosis was 5.9 years (1.1 years to 12.2 years). The most common clinical complaints were delayed height growth, followed by hypospadias or cryptorchidism in 2 cases, and special facial appearance in 1 case. Physical examination revealed 12 cases of Noonan syndrome with facial features, 9 cases with cryptorchidism and hypospadias, 10 cases with abnormal cardiac structure, and 10 cases with mental retardation; Twelve patients were detected with PTPN11 variations, 4 patients carried SOS2 variations, 2 cases were confirmed with variations in SHOC2 and SOS1. Six children received recombinant human growth hormone treatment, and their height increased by 4.0 (2.5-6.0) cm to varying degrees at 9 months. No adverse events occurred. Conclusions: Male Noonan syndrome is more frequently found with external genitalia. In addition to the high frequency of PTPN11 variation, the frequency of gene variation in SOS2 gene is higher than previously reported. All of the SOS2 variations are de novo. The syndrome phenotype profiles could vary with the admitted clinical departments. To understand the full picture of the syndrome, it is necessary to collect medical information from different departments.
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Síndrome de Noonan , Criança , Fácies , Feminino , Testes Genéticos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Mutação , Síndrome de Noonan/genética , Fenótipo , Estudos RetrospectivosRESUMO
Objective: To analyze the clinical, genetic characteristics and follow-up data of Chinese patients with hypophosphatasia (HPP). Methods: A retrospective analysis was conducted on six children with HPP admitted to the Department of Endocrinology, Genetics and Metabolism in Beijing Children's Hospital from October 2010 to January 2019. Summarized the clinical and follow-up data of all six patients, as well as the pathogenic variants of five children. Results: The serum alkaline phosphatase levels of all six children (five males and one female) were significantly reduced (2-49 U/L). The 6 patients aged from 2 months to 6 years and 4 months, 4 infantile HPP, 1 childhood HIP and 1 odonto HPP. The four patients with infantile HPP presented with anorexia, slow weight gain and hypercalcemia, whereas the one patient with childhood HPP and the other patient with odonto HPP had tooth loss. The patient with childhood HPP also manifested with motor dysfunction. Genetic testing was conducted for five patients and 4 unrelated Chinese families and revealed 10 variations in ALPL gene, including 7 missense variation, 1 insertion variation, 1 frameshift variation, 1 deletion variation.Of which 3 were novel (p.Y28C, p.268, F>L, p.A176V).One of the infantile patients lost follow-up and the other three deceased. The clinical conditions were much improved with medical intervention for patients with childhood, orodonto HPP. Conclusions: While HPP patients with different ages of onset present with common features, the prognosis differ significantly. The prognosis is good for patients with childhood, orodonto HPP and poor for patients with infantile HPP. Genetic testing is the main method for definitive diagnosis.
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Hipofosfatasia , Idoso , Fosfatase Alcalina/genética , Criança , Feminino , Seguimentos , Testes Genéticos , Humanos , Hipofosfatasia/diagnóstico , Hipofosfatasia/genética , Lactente , Masculino , Mutação , Estudos RetrospectivosRESUMO
Objective: To analyze the clinical and genetic features, as well as the treatment outcomes of two boys with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by gain-of-function mutations in the V2 vasopressin receptor gene (AVPR2). Methods: The clinical manifestations, genetic testing, therapeutic interventions and the outcomes of two boys with NSIAD hospitalized in the Department of Endocrinology, Beijing Children's Hospital in April 2019 were reported. A literature search with "Nephrogenic syndrome of inappropriate antidiuresis" and "AVPR2 gene" as keywords was conducted at the China national knowledge infrastructure (CNKI), the Wanfang Data Knowledge Service Platform, PubMed and Springer Link up to May 2020. Relevant published articles were reviewed. Results: The two cases presented with chronic and severe hyponatremia with hypo-osmolality, inappropriately elevated urinary osmolality and urinary sodium levels. The onset age was 5.25-years and 2 months respectively. AVPR2 sequencing revealed a previously described hemizygous activating mutation (c.409C>T, p.R137C) in both of boys, each inherited the variant from their mother. Patient 1 limited fluid intake by himself in his daily life, intravenous and oral sodium supplementations showed no significant increase of serum sodium level. Oral furosemide increased the serum sodium level and maintained it within normal range. The serum sodium and potassium levels were in the normal range during the 1-year follow-up period with oral furosemide. The serum sodium level of Patient 2 increased with restricting fluid intake and with salt supplementation. However, after he experienced respiratory infection, the plasma sodium level decreased. Subsequently, oral anti-infection medicine and furosemide were applied. The serum sodium level increased two days later and remained at a normal range afterwards. The boy was 1 year old with normal growth. He stopped taking furosemide after 4 months while taking 1 gram of salt per day, the blood sodium level maintained at normal range. Literature search identified no reports in Chinese journals, whereas 50 publications were found in English journals. A total of 30 NSIAD probands were reported and 16 of those (53%) had childhood onset, most presented with seizures. The majority had a hotspot change at the nucleotide position of 409 in AVPR2. Nine cases had an amino acid change as R137C and five cases as R137L. Fluid restriction and oral urea intake were main treatment options, no report so far was found with oral furosemide treatment. Conclusions: NSIAD presented with hyponatremia without any other specific presentations. Genetic testing for variants in AVPR2 is helpful for early diagnosis and timely treatment. The first two cases of oral furosemide treatment were reported by the article which helped to maintain a normal serum sodium level after limiting fluid intake and supplementing sodium which showed limited effect.