Objective To investigate the incidence of neonatal carnitine deficiency (PCD) in eight minority autonomous cities and counties in Hainan Province (Changjiang, Ledong, Dongfang, Baoting, Baisha, Qiongzhong, Wuzhishan and Lingshui). Methods A total of 18, 701 cases of newborn filter paper dried blood samples were collected from August 1, 2017 to July 31, 2018 in eight minority autonomous cities and counties in Hainan Province, including 10051 male infants and 8650 female infants. Tandem mass spectrometry and the non-derivatized multi-amino acid, carnitine and succinylacetone assay kits produced by PE were used to detect free carnitine (C0) and acylcarnitine (C2, C3, C16, C18, etc.).The carnitine spec-trum was reexamined with the recall of mothers and infants whose C0 was less than 10μmol/L. Blood sam-ples from those who were still low were sent to the Beijing McKinnon gene for genetic diagnosis, and the urine samples were sent to the Guangzhou Golden Field for urine gas chromatography. Results Among the 18701 newborns, 5 cases were diagnosed with PCD. The incidence of neonatal PCD was 2.67/10000 (5/18701). Two cases of Li mutation c.388GA, two cases of Han mutation P.R254X and one case of Miao mutation P. Y84N were confirmed by gene detection. The confirmed children were treated with L-carnitine to avoid metabolic disorders or myocardial and skeletal muscle damage. Conclusions The incidence of neonatal PCD is high in eight cities and counties in Hainan Province. The mutation sites of neonatal PCD are different in Li and Han. The tandem mass spectrometry screening of PCD can guarantee the quality of the birth population.

Objective: To investigate the prevalence of glucose-6-phosphate dehydrogenase (G6PD) gene mutation in newborns of Hainan Province, and to provide reference for prevention and treatment of G6PD deficiency in this region. Methods: Neonatal disease screening filter paper dry blood spots from all midwifery agencies were collected in 18 cities (counties) in Hainan Province from January to June 2016, G6PD activity screening test was conducted at Neonatal Disease Screening Center, Hainan Women and Children's Medical Center, and the enzyme activity was normal when fluorescence value > 1 600, and enzyme deficiency when fluorescence value ≤1 600. Referred to "China's Major Birth Defects and Genetic Diseases Survey and Biological Resources Collection", women newborns (3 371 cases) with fluorescence values ≤2 200 and men newborns (1 620 cases) with fluorescence values ≤1 700 were included in the study. Molecular screening was performed using multicolor melting curve analysis (MMCA), and the distribution and mutation characteristics of G6PD gene mutants were analyzed. Results: Among the 4 991 newborns, 2 111 cases with G6PD gene mutation, and the detection rate was 42.30% (2 111/4 991). A total of 27 G6PD gene mutants were found, including 14 single mutants and 13 composite mutants. The mutation detection rates of c.1376 G>T (21.42%, 1 069/4 991), c.1388 G>A (11.54%, 576/4 991), c.95 A>G (2.40%, 120/4 991) and c.871 G>A (2.24%, 112/4 991) were higher. The mutation detection rate (61.54%, 136/221) of Baisha County (inland area) was the highest, and the mutation detection rate (22.15%, 64/289) of Wenchang City (coastal area) was the lowest. The mutation detection rate (49.88%, 628/1 259) of the Li nationality was the highest. A total of 873 female heterozygotes were detected, including 13 gene mutants, of which 44.67% (390/873) with normal enzyme activity. The c.86 C>T heterozygous mutation was first detected in a sample of Li female with normal enzyme activity. Conclusions Hainan Province is the high incidence area of G6PD gene mutation, the most common mutations are c.1376 G>T, c.1388 G>A, c.95 A>G and c.871 G>A in newborns. Inland area is the high incidence area, and Li nationality is the high incidence population.

Objective To investigate the genetic carrier rate of thalassemia and its gene mutation types as well as the distribution characteristics among couples of reproductive age in Dongfang City of Hainan Province,and to provide a basis for making prevention and control strategies against thalassemia.Methods Samples were collected from 1 000 couples undergoing premarital and pregestational screenings for thalassemia in Dongfang City of Hainan Province from September 2012 to March 2013,in which the positive ones in preliminary screening were further tested by genetic diagnoses and the genotypes were retrospectively analyzed.Results Among 1 000 couples,322 spouses were diagnosed with thalassemia gene mutation and the carrying rate was 16.10％ (322/2 000).In those carriers,246 spouses were α-thalassemia and the carrying rate was 12.30％ (246/2 000),accounting for 76.40％(246/322) of all thalassemia carriers,among them,there were 197 cases of α-deficiency genotype,accounting for 61.18％ (197/322),32 carried mutated α-gene,accounting for 9.94％ (32/322),17 carried both deleted and mutated α-gene,accounting for 5.28％ (17/322);43 spouse were β-thalassemia and the carrying rate was 2.15％(43/2 000);33 spouse were both α-and β-thalassemia and the carrying rate was 1.65％ (33/2 000).In spouses diagnosed with α-thalassemia,the major genotype was-α37/αα,accounting for 19.25％ (62/322);the second ranked was-α4.2/αα,accounting for 17.70％ (57/322),and the third ranked was--SEA/αα,accounting for 8.70％ (28/322).In spouses diagnosed with β-thalassemia,the major genotype was CD41-42/N,accounting for 9.63％ (31/322).Conclusions The population carrying rate of thalassemia in Dongfang City of Hainan Province is high,and its major type is α-thalassemia.For the purpose of decreasing the birth rate of thalassemia,major,local public health department should attach great importance to thalassemia prevention,and strengthen premarital and pregestational screening for thalassemia.

Objective To investigate the clinical features, electrophysiological characteristics and treatment of stiff-person syndrome (SPS). Methods Medical records were retrospectively collected from 8 SPS patients to analysis their clinical features, laboratory studies, electromyography characteristics and treatment effect. Results All 8 patients presented with classic SPS, experienced progressive muscle stiffness, rigidity and spasm with paroxysmal exacerbation, which most frequently involved the thoracolumbar paraspinal muscles and bilateral lower limbs and other parts of body including thoracic and abdominal wall, upper limbs, neck, head and face. Five patients underwent electromyography and the results showed continuous motor unit activity (CMUA) in the involved muscles at rest. CMUA reduced markedly in 2 cases after intravenous diazepam. Anti-glutamic acid decarboxylase (GAD) antibody testing was positive in one of 5 tested cases. All 8 patients experienced partially symptomatic relief for their muscle rigidity and spasm after benzodiazepines. Combined immunotherapy further attenuated the symptoms in two cases receiving intravenous immunoglobulin (IVIG) and one case receiving glucorticosteroids, respectively. Symptoms were completely relieved following thymectomy in 2 cases with thymoma. Conclusion SPS is characterized by progressive muscle stiffness, rigidity and spasm with paroxysmal exacerbation affecting the axial trunk and bilateral lower limbs most frequently. Electromyography indicates CMUA in these involved muscles at rest. Treatment with benzodiazepines combined with immunotherapy can improve the neurological manifestations. Thymectomy can completely relieve symptoms of SPS in patiens with thymoma.

Objective To investigate the neonatal genetic carrier rate and genotype composition of thalassemia in Haikou city,and to evaluate the application of using dried blood spot specimens of neonates for population screening of thalassemia.Methods From January 2016 to December 2016,25% to 50% of all dried blood spot specimens of registered neonates were collected randomly by mechanical samping method in 30 hospitals of Haikou city everyday.Total of 6 864 samples were primarily analyzed by hemoglobin electrophoresis,and those with positive results were secondarily recalled for venous blood collection and subsequent genotyping tests.Feasibility of using neonatal dried blood spot specimens for population screening of thalassemia was retrospectively analyzed.Results A total of 6 864 neonatal dried blood spot specimens were analyzed.Out of 604 positive samples primarily screened by Hb electrophoresis, the positive rate was 8.80%,343 samples carried thalassemia gene mutations secondarily confirmed by genotyping test, the carrying rate was 5%(343/6 864),among which 81.92 %(281/343)were α-thalassemia,16.62%(57/343)were β-thalassemia and 1.46%(5/343)were both α-and β-thalassemia.In those α-thalassemia,the deleted α-gene types occupied 89.68%(252/281),the major genotype was --SEA/αα; the mutated α-gene types occupied 4.98%(14/281),the major genotype was αQS α/αα.In those β-thalassemia,there were 9 genotypes,the major genotype was CD41-42/N, occupying 61.40%(35/57).Conclusions The neonates have a relatively high carrying rate of thalassemia gene mutations in Haikou city, the genotype composition has geographical characteristics,and the major type is α-thalassemia.The method of using heel dried blood spot specimens on filter paper to screen thalassemia among neonates is advantageous and worthy of advocation.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.