RÉSUMÉ
To analyze the clinical features and genetic variants of a child with type 4 familial partial lipodystrophy (FPLD4) and the initial manifestation of diabetes.The male patient with the age of 13 years and 5 months, and the diabetes course was about 3 years, the patient was admitted to Children′s Hospital of Soochow University on November 10, 2021(4 th hospitalization at the hospital), in the course of diabetes, the children repeatedly suffered from diabetes ketoacidosis, and lipid metabolism complications gradually emerged.The gene sequencing showed that the proband and his mother carried dual gene mutations of PLIN1 c. 1325delG(p.G442Afs*99) and SPINK1 c. 194+ 2T>C(p.? ). The PLIN1 gene was the causal gene of FPLD4.The mutations of c. 1325delG in the PLIN1 gene had not been previously reported.Based on the clinical phenotype, family history and genetic testing findings, the patient was diagnosed as FPLD4.In addition, the mutation of SPINK1 c. 194+ 2T>C(p.? ) might increase the risk of chronic pancreatitis.This case report enriched the clinical characteristics and genotype data of FPLD4.Gene sequencing assisted the accurate diagnosis of the type of diabetes.The effects of dual gene mutations on disease progression should be concerned, which were of great significance to develop treatment regimen and disease management.
RÉSUMÉ
Objective:To investigate the value of serum insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS), anti-Müllerian hormone (AMH) and bone morphogenetic protein 6 (BMP-6) in prediction of rapidly progressive puberty(RPP) in girls.Methods:The data of 750 girls who visited the Department of Endocrinology, Metabolism and Genetic Disorders, Children′s Hospital of Soochow University from August 2017 to October 2018 because of breast development were retrospectively analyzed.After following up these girls for 6 months to 1 year, those who were lost to follow up, received early treatment and failed to meet the inclusion criteria were excluded.The remaining 138 girls were divided into the central precocious puberty group (CPP, 32 cases), the early puberty with RPP group (EP-RPP, 33 cases), the early puberty with slow progression puberty group (EP-SPP, 32 cases) and RPP group (41 cases) according to the inclusion criteria.The healthy control group consisted of 33 undeveloped girls aged 8 to 9 who underwent physical examination in the same hospital over the same period.The serum concentrations of IGF-1, DHEAS, AMH and BMP-6 were measured.The general information, clinical manifestations, laboratory examination results and radiological features were compared among different groups.Statistical analysis was performed by using SPSS 22.0, and the receiver operating characteristic curve (ROC) was drawn to investigate the value of IGF-1, DHEAS, AMH and BMP-6 in prediction of RPP.Results:(1)The serum follicle stimulating hormone(FSH) peak value was 15.10(13.86-19.80) IU/L in the EP-SPP group, 11.99(9.18-16.16) IU/L in the EP-RPP group and 11.43(9.37-15.63) IU/L in the RPP group.The ratio of serum FSH/luteinizing hormone(LH) peak values was 3.20(2.44-4.58) in the EP-SPP group, 1.86(1.05-3.16) in the EP-RPP group and 0.76(0.49-0.99) in the RPP group.The serum FSH peak value and the ratio of serum FSH/LH peak values in the EP-SPP group were significant higher than those in the EP-RPP group(all P<0.05). There was no significant difference in the serum FSH peak value between the EP-RPP group and the RPP group( P>0.05). (2)The serum IGF-1 levels of the healthy control group, EP-SPP group, EP-RPP group, CPP group and RPP group were 166.00(126.50-188.00) μg/L, 199.00(170.50-262.50) μg/L, 252.00(233.00-291.50) μg/L, 288.00(252.00-376.00) μg/L and 382.00(264.0-499.50) μg/L, respectively.The serum IGF-1 levels of the EP-SPP group, EP-RPP group, CPP group and RPP group were all significantly higher than those in the healthy control group (all P<0.05). The serum IGF-1 levels in the EP-RPP group were higher than those in the EP-SPP group( P<0.01). As the puberty rapidly progressed, the serum IGF-1 levels gradually increased.The RPP group had the highest IGF-1 levels, and the difference in IGF-1 levels between the RPP group and EP-RPP group was statistically significant( P<0.01). (3)The serum DHEAS levels were 41.65(14.80-59.88) μg/L in the healthy control group, 42.50(30.15-79.83) μg/L in the EP-SPP group, 52.32(43.08-98.54) μg/L in the CPP group, 63.30(34.00-81.55) μg/L in the EP-RPP group and 70.89(51.85-100.02) μg/L in the RPP group.The DHEAS levels of the healthy control group, EP-RPP group and RPP group gradually increased.The RPP group had the highest DHEAS levels.There was significant difference in DHEAS levels among the healthy control group, EP-RPP group and RPP group ( P<0.05). There was no significant difference in DHEAS levels among the EP-SPP group, CPP group and EP-RPP group( P>0.05). (4)The serum AMH and BMP-6 levels in the EP-RPP group, EP-SPP group, RPP group, CPP group and healthy control group were not significantly different( P>0.05). (5)The area under the ROC curve of serum IGF-1 levels was 0.765, the cut-off value was 232.5 μg/L, the specificity for the cut-off value was 83.30%, and the sensitivity was 75.00%.The combined area under the ROC curve of the serum FSH peak value and the ratio of serum FSH/LH peak values was 0.795. Conclusions:Serum IGF-1 levels and the combination of the serum FSH peak value and the ratio of serum FSH/LH peak values can be used as effective indicators of slowly and rapidly progressive puberty in early adolescent girls.Serum DHEAS cannot be used as an early warning index of RPP, but it plays a critical role in the regulation of puberty initiation and process.Serum DHEAS levels may be related to the Tanner stage.