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Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.
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Objective To investigate the short-term efficacy of dapagliflozin in the treatment of non-diabetic patients with severe aortic stenosis after transcatheter aortic valve replacement(TAVR).Methods A total of 84 non-diabetic patients with severe aortic stenosis after TAVR who were admitted to Zhengzhou Cardiovascular Hospital from March 2019 to September 2022 were selected as research subjects.According to the postoperative treatment,the patients were divided into control group and observation group,with 42 patients in each group.Patients in both groups underwent TAVR.The patients in the control group were given routine treatments such as antiplatelet drugs,cardiac remodeling improvement drugs,and diuretics after TAVR;patients in the observation group were given dapagliflozin 10 mg daily for 6 months in addition to treatment in the control group.The left ventricular ejection fraction(LVEF),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),aortic valve peak gradient(AVPG)and aortic valve peak velocity(AVPV)of patients in the two groups were measured by using an ultrasound diagnostic instrument before surgery,3 days and 6 months after TAVR;before surgery and 6 months after the TAVR,low-density lipoprotein cholesterol(LDL-C)in serum of patients in the two groups was detected by direct measurement method,lipoprotein a[Lp(a)]level in serum was detected by latex agglutination reaction method,hypersensitive C-reactive protein(hs-CRP)level in serum was detected by rate scattering turbidimetry;the levels of N-terminal pro B-type natriuretic peptide(NT-proBNP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1 β)in serum were detected by using enzyme-linked immunosorbent assay;the glycated hemoglobin level of patients in the two groups was measured by ion exchange chromatography.Results There was no statistically significant difference in LVEF,LVESD and LVEDD of patients in the two groups before and 3 days after surgery(P＞0.05);after 3 days of surgery,the AVPG and AVPV of patients in the two groups were significantly lower than those before surgery(P＜0.05).Six months after surgery,the LVEF of patients in the two groups was significantly higher than that before and 3 days after surgery,while LVESD,LVEDD,AVPG and AVPV were significantly lower than those before and 3 days after surgery(P＜0.05).There was no statistically significant difference in LVEF,LVESD,LVEDD,AVPG and AVPV between the control group and the observation group before and 3 days after surgery(P＞0.05).After 6 months of surgery,the LVEF of patients in the observation group was significantly higher than that in the control group,while LVESD and LVEDD were significantly lower than those in the control group(P＜0.05);there was no statistically significant difference in AVPG and AVPV of patients between the observation group and control group(P＞0.05).Before surgery,there was no statistically significant difference in body mass index(BMI),LDL-C and Lp(a)of patients between the two groups(P＞0.05).Six months after surgery,the BMI,LDL-C and Lp(a)of patients in the two groups were significantly lower than those before surgery,and the BMI,LDL-C and Lp(a)of patients in the observation group were significantly lower than those in the control group(P＜0.05).Before surgery,there was no statistically significant difference in the hs-CRP,NT-proBNP,IL-6,TNF-α and IL-1 β of patients between the two groups(P＞0.05);six months after surgery,the hs-CRP,NT-proBNP,IL-6,TNF-α and IL-1 β of patients in the two groups were significantly lower than those before surgery,and the hs-CRP,NT-proBNP,IL-6,TNF-α and IL-lβ of patients in the observation group were significantly lower than those in the control group(P＜0.05).There was no statistically significant difference in glycated hemoglobin of patients between the two groups before and six months after surgery(P＞0.05),and no statistically significant difference in glycated hemoglobin of patients in the two groups six months after surgery compared with that before surgery(P＞0.05).Conclusion Dapagliflozin can effectively improve cardiac structural remodeling,regulate lipid metabolism,reduce the expression of inflammatory factors and promote the recovery of heart function in non-diabetic patients with severe aortic stenosis after TAVR.
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Objective To summarize the clinical features of 22 probands diagnosed with congenital muscular dystrophy (CMD),and to provide genetic counseling and prenatal diagnosis for 23 fetuses of these pedigrees.Methods Data of 22 CMD patients who were treated in the Pediatric Department of Peking University First Hospital during October 2006 to March 2016 were analyzed.Informed written consents for participation in this study were obtained from the parents or guardians.Prenatal diagnosis was performed using DNA samples extracted from fetal villus cells of 12 cases at 11-13 gestational weeks and amniotic fluid of 11 cases at 18-22 gestational weeks.Direct DNA sequencing by polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) were used to detect CMD-related gene mutations.Linkage analysis of short tandem repeats (STRs) was used to identify maternal blood contamination and biological parents.Results Thirteen out of the 22 probands with CMD were diagnosed with congenital muscular dystrophy type 1 A (MDC1A),and all of them carried compound heterozygous mutations in LAMA2 gene.Prenatal diagnosis of 13 fetuses from these pedigrees found that four fetuses were wild-type,seven were heterozygotes and two carried the same mutations as their proband.Three probands with LMNA-related congenital muscular dystrophy (L-CMD) carried de novo mutations in LMNA gene.In these pedigrees,two fetuses were wild-type and one whose mother was mosaicism carried the same mutations as the proband.One proband with Ullrich congenital muscular dystrophy carried compound heterozygous mutations in COL6A2 gene and the fetus of the same pedigree was wild-type.Five probands were diagnosed with α-dystroglycanopathies.And among them,two cases of muscle-eye-brain disease (MEB) carried compound heterozygous mutations in POMGnT1 gene and the fetuses of the two peidgrees were heterozygotes;one case of congenital muscular dystrophy type 1C (MDC1C) had compound heterozygous mutations in FKRP gene and the fetus carried the same mutations;one patient diagnosed with POMGnT1-related congenital muscular dystrophy with mental retardation (CMD-MR) carried compound heterozygous mutations in POMGnT1 gene,and the fetus was positive for the same mutations;one proband with POMT1-related CMD-MR was positive for compound heterozygous mutations in POMT1 gene and the results of prenatal diagnosis for two fetuses of this pedigree showed that the first fetus had the same mutations as the proband,while the second was heterozygote.Conclusions No effective therapeutic method is available for CMD.Therefore,accurate genetic counseling and prenatal diagnosis are necessary to prevent CMD child from birth.