Objective:To report a SPTLC2 gene mutation in a family with a phenotype of Charcot-Marie-Tooth disease.Methods:To screen the family of patients with pathogenic mutations of SPTLC2 gene from the database of hereditary peripheral neuropathy in the Department of Neurology, Peking University First Hospital, and to collect their clinical data, peripheral nerve conduction examination, nerve ultrasound examination, pathological examination of the peroneal nerve and whole exome sequencing results of prohand.Results:One family was screened, the proband was a 16-year-old female with 4 years of sensory loss and anhidrosis of both lower limbs and 16 months of walking difficulty who admitted to Peking University First Hospital in January 2022. Physical examination showed sensory loss, dry skin and weakness in distal limbs. Her father had numbness and dry skin in the distal lower limbs from childhood,weakness and atrophy of his lower limbs in adulthood. He died at age of 52 years old. The nerve conduction study revealed no action potentials of the sensory and motor nerves of the lower limbs in the proband. The amplitude of the compound muscle action potential of the motor conduction of the bilateral ulnar nerve and median nerve decreased, and the nerve conduction velocity of the bilateral median nerve were 32 m/s and 24 m/s. Neurosonography showed thickening of peripheral nerves. Sural biopsy revealed severe loss of myelinated and unmyelinated nerve fibers with onion bulbs formation. SPTLC2 gene showed a known heterozygous p.G435V mutation. The lower limb weakness was improved after oral L-serine.Conclusions:SPTLC2 gene mutation can lead to an intermediate Charcot-Marie-Tooth disease phenotype. L-serine can improve the limb weakness.

Objective:To study the prevalence and clinical characteristics of hepatitis D patients.Methods:A total of 832 144 HBsAg positive persons who were from infectious department of Southwest Hospital Affiliated to Army Military Medical University were screened from January 1, 2010 to December 31, 2020. A total of 13 585 subjects completed relevant Hepatitis Delta virus (HDV) biomarker tests, 157 HDV patients were evaluated. The mean age was 53 ± 13 years, with a range of 22-85 years. The majority of these subjects were male. The prevalence, clinical characteristics, the outcome of 28 days follow-up and the influencing factors of the outcome were analyzed.Results:In recent 10 years, the screening rate related to hepatitis D was only 1.6% (13 585/832 144), and the screening rate was the highest in 2011, up to 4.13% (962/23 289); The positive rate of screening was only 1.17% (157/13 346). In 2012, the positive rate of screening was the highest, up to 3.56% (58/1627). In Southwest Hospital, the source of disease was 66.24% (104/157) in Chongqing, 22.93% (36/157) in Sichuan, 8.28% (13/157) in Guizhou, 1.27% (2/157) in Yunnan, and 0.64% (1/157) in each of Jiangxi and Tibet. Of 157 patients, 29 (18.47%) had non-cirrhotic with chronic low bilirubin hepatitis, 23.57% (37/157) was non-cirrhotic with chronic high bilirubin hepatitis, 28.66% (45/157) had acute-on-chronic liver failure (ACLF), 27.39% (42/157) had compensated cirrhosis or decompensated cirrhosis, and 1.91% (3/157) had primary hepatocellular carcinoma. The incidence of disease progression was 48.89% (22/48) of chronic-on-acute liver failure>33.33%(1/3) of primary hepatocellular carcinoma>25.58%(11/43) of compensated or decompensated cirrhosis>18.92%(7/37) of non-cirrhotic with chronic high bilirubin hepatitis>6.90%(2/29) of non-cirrhotic with chronic low bilirubin hepatitis ( P<0.05). Among them, 7.64%(12/157) had hepatic encephalopathy, and the rate of disease progression was 83.33%(10/12) ( P<0.05); 3.82% (6/157) of them had combined with other hepatophilic viruses including hepatitis C virus (HCV), Epstein-barr virus, (EBV), Cytomegalovirus (CMV) infections. Logistic regression analysis showed that old age, complication with hepatic encephalopathy, hyperbilirubinemia and prolonged coagulation time were independent risk factors affecting the outcome of hepatitis D. Conclusions:In recent 10 years, the screening rate of hepatitis D is low and the positive rate is not high. It should be noted that HDV infection can accelerate the progress of hepatitis and increase the risk of adverse liver outcomes.

Objective To report the clinical and peripheral neuropathological findings in two patients with autosomal recessive Charcot-Marie-Tooth disease 2K(AR-CMT2K).Methods Case one was a nine year-old girl.She had distal weakness of lower limbs for six years, with calf atrophy and contracture of Achilles tendon for three years.Case two was an eight year-old boy.He had distal weakness of lower limbs with contracture of Achilles tendon and calf muscle atrophy for three years, and proximal weakness of low limbs for two years.The motor nerve conduction velocities in median nerves were 48.1 m/s in case one and 47.6 m/s in case two.The compound motor action potential amplitude of median nerves decreased by 46% in case one and 69% in case two.Sural nerve biopsies and gene targeted next-generation sequencing were performed in both patients.Results Density of myelinated fibers was 8 407/mm2 in case one and 7 714/mm2 in case two.The ratio of myelinated fibers with diameter over 8 μm was 2.6% in case one and 0 in case two.Both patients had small regenerating cluster of myelinated fibers.Thin myelinated fibers appeared in case one.In case two, atypical onion bulb formations with focal folded myelin appeared, and electromicroscopy revealed mitochondrial aggregate in axons.Compound heterozygous mutations of ganglioside-induced differentiation associated protein 1 gene were detected in both patients, including c.767A>G(p.H256R) and c.466G>A (p.A156T) in case one and c.767A>G and 845G>A(p.R282H) in case two.Conclusions Contracture of Achilles tendon may appear in early childhood of AR-CMT2K patients.The main pathological changes in sural nerve are loss of large myelinated fibers, mitochondrial aggregate in axons and myelin abnormalities.

Objective To analyze the normal reference values of left ventricular longitudinal peak systolic strain (LS) and strain rate (LSr) by two-dimensional speckle tracking imaging (2D-STI) in healthy children at different ages.Methods Clinical ultrasound data of 330 healthy children who taking physical examination in our hospital from September 2015 to November 2016 were collected and retrospectively.They were divided into 7 groups according to their ages,that is,neonate group (0 to 28 days old),infant group (28 days to 1 year old),toddle group (1 to 3 years old),pre-school group (3 to 6 years old),school age group (6 to 9 years old),pre-adolescence group (9 to 13 years old) and adolescence group (13 to 18 years old).2D-STI was performed in the 3 apical projections of left ventricle (LV).The regional peak systolic longitudinal strain and strain rate of LV were measured.Results ① Significant differences were found in the LS and LSr values from 6 segments of the same wall (P ＜ 0.05),and the LS and LSr values were gradually increased from basal segment to apical segment.②There were no significant differences in the LS,LSr and global LS (GLS) values of 18 segments between sexes (P ＞ 0.05).③ Except the basal segments of posterior wall,inferior wall and posterior septum,LS value was gradually elevated with the increase of age (LS ＜LSinfant ＜ LStoddler,pre-shool and school age ＜ LSpre-adolescence and adolescence),So was GLS value.④LS in 18 segments had a positive correlation with age,and the value of apical segment in lateral wall was most remarkably correlated (r =0.551,P ＜0.01);Regional LS had a negative correlation with heart rate,and that of middle segment in lateral wall was the most apparent (r =-0.625,P ＜ 0.01);GLS was positively influenced by age (r =0.665,P ＜ 0.01) and negatively affected by heart rate (r =-0.625,P ＜ 0.01).⑤The heterogeneities were found in the correlations of regional LSr with age and heart rate in segments and in the LSr among different age groups.Conclusion Normal reference values of LV peak LS and LSr are established for healthy children at different ages,and they possess their own characteristics.

Chronic liver diseases in children greatly affect their growth and development and quality of life in future.There are many causes of chronic liver diseases in children,and such causes,diet,and treatment guidance are closely associated with prognosis.This article discusses the guidance and follow-up of common chronic liver diseases in children,such as infantile cholestatic liver disease,chronic hepatitis B,hepatolenticular degeneration,and nonalcoholic fatter liver disease,in order to deepen the understanding of these diseases among patients,raise the awareness of follow-up in medical staff,and improve the cure rate of liver diseases with different causes and children's quality of life.

Objective To analyze the differences of the clinical and neuropathological features among the common Charcot-Marie-Tooth disease (CMT) subtypes.Methods There were 81 CMT patients confirmed by genetic testing from 2005 to 2015 in Department of Neurology,Peking University First Hospital,including 31 cases of CMT1A (38.3％),19 cases of CMTX1 (23.5％),16 cases of CMT2A2 (19.8％) and 15 cases of 9 rare types of CMT (1.2％-4.9％).We compared the onset age,duration,muscles weakness of legs,frequency of pes cavus,and main pathological changes of the sural nerve biopsy in 48 cases of the common CMT subtypes.Results The mean age of the onset was (12.00 ± 6.77) years in CMT1A patients,(11.81 ±4.65) years in CMTX1 patients and (5.00 ±2.68) years in CMT2A2 patients (Brown-Forsythe test,P =0.001).The duration was (12.00 ± 6.75) years in CMT1A patients,(8.50 ± 4.75) years in CMTX1 patients and (5.00 ± 2.73) years in CMT2A2 patients (Brown-Forsythe test,P =0.001).The muscle force of the dorsi flexors was Ⅳ (0,Ⅴ) in CMT1A patients,Ⅲ + (0,Ⅳ) in CMTX1 patients and 0 (0,Ⅳ) in CMT2A2 patients (H =11.359,P =0.020).The pes cavus appeared in 15/23 cases of CMT1A,10/16 cases of CMTX1 and 1/9 cases of CMT2A2 (Fisher test,P=0.017).The leukoencephalopathy appeared only in 3 cases of CMTX1 and the visual loss appeared only in 3 cases of CMT2A2.The onion-bulb formations of myelinated fibers appeared in 23/23 cases of CMT1 A,5/16 cases of CMTX1 and 2/9 cases of CMT2A2(Fisher test,P =0.000).The axonal regeneration appeared in 16/23 cases of CMT1A,16/16 cases of CMTX1 and 9/9 cases of CMT2A2 (x2 =7.666,P =0.016).There were significant differences among the three common CMT subtypes in the above parameters.Conclusions CMT1A,CMT2A2 and CMTX1 are the most common subtypes of CMT in the present study.For the clinical diagnosis,more attention should be paid to the onset of the disease,duration,muscles weakness,pes cavus,cerebral symptoms and visual loss.The present frequency of onion-bulb and the axonal regeneration of myelinated fibers help the different pathological diagnosis among them.

Objective To summarize the clinical features of Chinese patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes ( MELAS).Methods A total of 190 patients with MELAS who presented to Peking University First Hospital between 1997 and 2015 were recruited.Among 190 patients, 175 were identified carrying mitochondrial DNA mutations, and the remaining 15 patients were diagnosed by muscle biopsy.The clinical features, including predisposing factors of stroke-like episodes, the onset symptoms and frequencies of various manifestations were analyzed and reported.Results In our cohort of MELAS patients, the male-to-female ratio was 1.44∶1.The median age of onset was 14 years ( from 7 months to 45 years).The peak onset ages were 8-12 years.The median onset age of the first stroke-like episode was 16 years ( from 1 to 53 years ).There were 66 ( 46.15%) patients who had predisposing factors before the onset, and fatigue and upper respiratory tract infection were the most common predisposing factors of stroke-like episodes in these patients ( 37.88%, 25/66 and 34.85%, 23/66, respectively).Other predisposing factors included emotional agitation, drinking alcohol, trauma, withdrawal of antiepileptic drugs, being frightened, satiation and hunger.Stroke-like episodes appeared in 70.53%(134/190) patients as an onset symptom and developed in all patients with disease progression.The neurological manifestations included seizure ( 89.42%, 169/189 ) , mental retardation or dementia (82.87%, 150/181), headache (74.30%, 133/179), hemianopia or cortical blindness (67.72%, 107/158), exercise intolerance (50.87%, 88/173), hemiplegia or hemianesthesia (47.44%, 74/156), sensorineural deafness (46.20%, 85/184), aphasia (39.47%, 60/152), behaviour disorder (17.71%, 31/175) and ophthalmoplegia ( 9.60%, 17/177 ).The manifestations of extra-nervous systems included hirsutism (67.57%, 100/148), vomiting (65.58%, 101/154), fever (62.07%, 90/145), short stature (45.32%, 63/139), diarrhea or constipation (43.48%, 70/161), low body mass index (26.62%, 37/139), diabetes mellitus (20.79%, 37/178) and kidney disease (3.16%, 6/190).Conclusions The majority of the patients in this study have the disease onset during childhood.There are more male MELAS patients than females.Most common clinical manifestations are seizure, mental retardation or dementia, headache, cortical blindness, hirsutism, vomiting and fever in this patient group.

Objective To explore clinical and muscular pathological features of statin-induced myopathy.Methods Nine patients were enrolled in this study,who were diagnosed as statin-induced myopathy by muscle biopsy in Peking University First Hospital from April,2012 to October,2014.The clinical data and pathological findings were analyzed.Results The exposure time to statins varied from 4 days to 4 years in the total of 9 patients,6 males and 3 females,with the average age of 63 ± 6 (55 to 74) years old.Three patients suffered from myalgia and 6 patients complained of weakness mainly at the proximal limbs,while no symptoms occured in 3 patients.Serum creatine kinase (CK) increased in all patients with the maximum value varied from 468 to 8 000 U/L.Serum myositis antibodies were tested in 7 patients and all were negative.Electromyogram was performed in six patients with myogenic damage found in 2 patients.MRI of bilateral thigh muscle was carried out in six patients with muscle edema and mild fatty infiltration found in 2 patients.All patients underwent skeletal muscle biopsy with histochemical and immunohistochemical staining.The main muscular pathological features were muscle fiber atrophy,necrosis,regeneration and increased lipid droplets.Ragged blue fiber,cytochrome C oxidase-negative muscle fibers and decreased NADH activity were observed in some patients.MHC-Ⅰ expressed in the sarcolemma of muscle fibers at various levels.Mild C5b-9 staining was found in the endomysium,capillary and cytoplasm.Symptoms and the level of CK were improved in 7 patients after discontinuing statins or changing to another statin,while the immunosuppressive therapy were used in 2 patients and shown to be effective.Conclusions Statin induced myopathy is self-limiting in most patients,with improvement after discontinuation of statins.Few patients with autoimmune necrotic myopathy need immunosuppressive therapy.

OBJECTIVETo summarize the clinical characteristics of an infant with chronic myelogenous leukemia (CML) and the effects of imatinib on the case.

METHODThe clinical features of an infant with CML, who was treated with imatinib in the Norman Bethune International Peace Hospital at June 2009, were retrospectively analyzed and the reports in literature were reviewed. The 1-year-old boy suffered from recurrent low-degree fever and pallor. He had a moderate anemia, distended abdomen and marked splenomegaly. Bone marrow aspiration revealed CML in chronic phase)CP). The t (9; 22))q34; q11) could be detected and BCR-ABL (p210) was positive. The boy was diagnosed as CML-CP and treated with imatinib 100 mg per day. There were 10 related papers and more than 100 child CML patients were reported as retrieved from CNKI)from its establishment to August 2014) and Wanfang Database)from its establishment to August 2014) when "Child", " Chronic" and "Leukemia" were used as keywords. And there were 30 related papers including 400 cases from PubMed Database (from its establishment to August 2014) and one detailed report of an infant with CML was retrieved when "childhood" and "chronic myeloid leukemia" "imatinib" were used as keywords. The clinical effects of imatinib in infant CML cases were analyzed and summarized based on the literature.

RESULTThe boy obtained a complete hematologic response (CHR) at the 6th week of diagnosis, a complete cytogenetic response (CCyR) at the 3rd month and a complete molecular response)CMR) at the 12th month without side effect. This boy grows very well and after a 62-month follow-up, his disease was stable. According to the domestic literature, 5 children CML cases aged 6 -12 years were treated with imatinib without side effects and got complete hematologic response (CHR) after 2-month-therapy. The dose, metabolic characteristics and clinical observation of imatinib can be found in foreign literature and imatinib showed good response with good tolerance in children with CML. Imatinib is regarded as the first line drug for children CML. But it may affect the development of the children.

CONCLUSIONThe children with CML-CP had a good response to imatinib, but more experience in the treatment of children with CML with iniatinib is needed.

Anemia ; Antineoplastic Agents ; therapeutic use ; Fusion Proteins, bcr-abl ; Humans ; Imatinib Mesylate ; therapeutic use ; Infant ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Male ; Remission Induction ; Retrospective Studies