OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with Hereditary spastic paraplegia type 3A (SPG3A) and the genotype-phenotype correlation. METHODS: A three-generation pedigree presented at Huantai Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Whole-exome sequencing (WES) and pedigree analysis was carried out. Candidate variant was validated by Sanger sequencing of the members from the pedigree. Haplotype analysis was used to trace the origin of the variant, and pathogenicity was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-12). RESULTS: A c.1024C>T (p.Pro342Ser) variant of the ATL1 was identified in the four affected members, including the proband, but none of the three unaffected relatives. Haplotype analysis suggested that the variant was derived from the proband's mother and has co-segregated with the disease phenotype. Based on the guidelines of the ACMG, it was classified as likely pathogenic. CONCLUSION The ATL1 c.1024C>T (p.Pro342Ser) variant probably underlay the pathogenesis in this pedigree. Above finding has enriched the mutational spectrum of ATL1 and phenotypic spectrum of SPG3A in the Chinese population, and enabled genetic counseling for this pedigree.
Humans ; Pedigree ; Spastic Paraplegia, Hereditary/genetics* ; Male ; Female ; Asian People/genetics* ; Adult ; Haplotypes ; Membrane Proteins/genetics* ; Exome Sequencing ; GTP-Binding Proteins/genetics* ; Mutation ; Middle Aged ; China ; Genetic Association Studies ; East Asian People

OBJECTIVE: To investigate the clinical manifestations and genetic characteristics of a child with glycogen storage disease type III (GSD-III) complicated with Guillain-Barré syndrome (GBS) caused by AGL gene variants, and to analyze the pathogenesis, potential correlation, treatment and prognosis of the two diseases. METHODS: A child with GSD-III who visited the General Hospital of Ningxia Medical University due to "limb weakness for more than ten days" in July 2024 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected for whole exome sequencing and Sanger sequencing. Candidate variants were verified, and pathogenicity analysis was conducted for the variant sites. This study was approved by the Medical Ethics Committee of General Hospital of Ningxia Medical University (Ethics No.: KYLL-2025-1984). RESULTS: The child has presented with inability to stand or walk independently, difficulty in grasping, accompanied by numbness and pain at the distal end, choking when drinking water, occasional non-projectile vomiting, and enlargement of liver and spleen. Laboratory tests showed abnormal liver function and a significant increase in creatine kinase. Color Doppler ultrasound of the heart showed an enlarged left atrium and mild regurgitation of mitral and tricuspid valves. Genetic testing confirmed that he has harbored compound heterozygous variants of the AGL gene, namely c.1611G>A (p.E537E) and c.579del (p.W194Gfs*7), which were inherited from his father and mother, respectively. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the two variants were respectively predicted as variant of unknown significance (PM2_Supporting+PM3+PP3_Supporting) and likely pathogenic (PVS1+PM2_Supporting). Electrophysiological examination confirmed that the child had severe damage to the motor and sensory nerves accompanied by axonal injury, which was consistent with the axonal variant type of GBS -acute motor and sensory axonal neuropathy. After a clear diagnosis, the child was treated with intravenous human immunoglobulin. His condition deteriorated progressively, presenting with breathing difficulties, liver failure, and gastrointestinal bleeding, and eventually deceased due to multiple organ failures. CONCLUSION The etiology of GSD-III and GBS involves multiple aspects such as genetics, metabolism and immunity. In clinical practice, it should be noted that similar clinical manifestations may occur in both conditions. Close attention should be paid to the patients' blood glucose, blood gas, coagulation function and liver function, etc. Clinical intervention should be carried out as early as possible to improve the prognosis.
Humans ; Male ; Guillain-Barre Syndrome/complications* ; Glycogen Storage Disease Type III/complications* ; Mutation ; Child

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. METHODS: A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56). RESULTS: The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c.289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. CONCLUSION The homozygous c.289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.
Humans ; Male ; Spastic Paraplegia, Hereditary/genetics* ; Child, Preschool ; Female ; Exome Sequencing ; Child ; Infant ; Adaptor Protein Complex 4/genetics* ; Phenotype ; Mutation

Miller Fisher syndrome（MFS）is a clinical variant of Guillain-Barre syndrome（GBS）and has the main clinical features of ataxia，ophthalmoplegia，and tendon areflexia，with pupil changes and abnormal pupillary light reflex in rare cases. There are generally no symptom fluctuations，and positive anti-GQ1b IgG antibodies can be detected in some patients. This article reports a case of MFS with positive anti-GQ1b，anti-GT1a，and anti-sulfatide antibodies and fluctuating extraocular muscle paralysis as the initial presentation，accompanied by bilateral pupil dilation，delayed light reflex，and numbness and weakness in the limbs. The symptoms are rare and atypical，which may easily lead to misdiagnosis in clinical practice.
Miller Fisher Syndrome ; Ophthalmoplegia

Different autoantibodies can be detected in patients with coronavirus disease 2019 (COVID-19). It is reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could induce autoimmune diseases (AID), including children's multisystem inflammatory syndrome (MIS-C), Guillain Barre syndrome (GBS), Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP) and thyroid autoimmune diseases. This article mainly reviews the similarities between COVID-19 and AID, the possibility of COVID-19 inducing AID, the risk of AID patients infected or vaccinated against COVID-19. The purpose is to provide strategies for the prevention, management and treatment of AID during the epidemic.
Child ; Humans ; COVID-19 ; SARS-CoV-2 ; Guillain-Barre Syndrome/therapy* ; Epidemics

Humans ; Herpesvirus 3, Human ; Myelitis, Transverse/complications* ; Guillain-Barre Syndrome/complications* ; Herpes Zoster/complications* ; Varicella Zoster Virus Infection/complications*

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with hereditary spastic paraplegia type 30 (HSP30). METHODS: A proband presented at the Second Hospital of Shanxi Medical University in August 2021 was selected as the study subject. The proband was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband was found to have harbored a heterozygous c.110T>C variant in exon 3 of the KIF1A gene, which can cause substitution of isoleucine by threonine at position 37 (p.I37T) and alter the function of its protein product. The same variant was not found in his parents, elder brother and elder sister, suggesting that it has a de novo origin. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PM2_Supporting+PP3+PS2). CONCLUSION The c.110T>C variant of the KIF1A gene probably underlay the HSP30 in the proband. Above finding has enable genetic counseling for this family.
Humans ; Male ; East Asian People ; Kinesins/genetics* ; Mutation ; Pedigree ; Spastic Paraplegia, Hereditary/genetics* ; Female

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a child with Hereditary spastic paraplegia (HSP). METHODS: A child with HSP who was admitted to the Third Affiliated Hospital of Zhengzhou University on August 10, 2020 due to discovery of tiptoeing for 2 years was selected as the study subject, and relevant clinical data was collected. Peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA. And trio-whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing. Bioinformatic software was used to analyze the conservation of variant sites. RESULTS: The child was a 2-year-and-10-month-old female with clinical manifestations including increased muscle tone of lower limbs, pointed feet, and cognitive language delay. Trio-WES results showed that she had harbored compound heterozygous variants of c.865C>T (p.Gln289*) and c.1126G>A (p.Glu376Lys) of the CYP2U1 gene. And the corresponding amino acid for c.1126G>A (p.Glu376Lys) is highly conserved among various species. Based on guidelines from the American College of Medical Genetics and Genomics, the c.865C>T was predicted as a pathogenic variant (PVS1+PM2_Supporting), and c.1126G>A was rated as a variant of uncertain significance (PM2_Supporting+PM3+PP3). CONCLUSION The child was diagnosed with HSP type 56 due to compound variants of the CYP2U1 gene. Above findings have enriched the mutation spectrum of the CYP2U1 gene.
Female ; Humans ; Cytochrome P450 Family 2/genetics* ; Mutation ; Pedigree ; Phenotype ; Spastic Paraplegia, Hereditary/genetics* ; Infant

POEMS syndrome is a rare disease caused by monoclonal plasma cell proliferative disorder.The typical signs include peripheral neuropathy,organ enlargement,endocrine disease,M proteinemia,and skin changes.In clinical practice,the atypical,complex,and changeable clinical manifestations of this syndrome can easily lead to misdiagnosis and missed diagnosis.A case of POEMS syndrome with peripheral edema and ascites as the main manifestations is reported in this paper.
Humans ; Ascites/etiology* ; POEMS Syndrome/diagnosis* ; Edema/diagnosis* ; Skin

OBJECTIVE: To analyze and compare the characteristics and causes of F wave changes in patients with Charcot-Marie-Tooth1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Thirty patients with CMT1A and 30 patients with CIDP were enrolled in Peking University Third Hospital from January 2012 to December 2018. Their clinical data, electrophysiological data(nerve conduction velocity, F wave and H reflex) and neurological function scores were recorded. Some patients underwent magnetic resonance imaging of brachial plexus and lumbar plexus, and the results were analyzed and compared. RESULTS: The average motor conduction velocity (MCV) of median nerve was (21.10±10.60) m/s in CMT1A and (31.52±12.46) m/s in CIDP. There was a significant difference between the two groups (t=-6.75, P < 0.001). About 43.3% (13/30) of the patients with CMT1A did not elicit F wave in ulnar nerve, which was significantly higher than that of the patients with CIDP (4/30, 13.3%), χ²=6.65, P=0.010. Among the patients who could elicit F wave, the latency of F wave in CMT1A group was (52.40±17.56) ms and that in CIDP group was (42.20±12.73) ms. There was a significant difference between the two groups (t=2.96, P=0.006). The occurrence rate of F wave in CMT1A group was 34.6%±39%, and that in CIDP group was 70.7%±15.2%. There was a significant difference between the two groups (t=-5.13, P < 0.001). The MCV of median nerve in a patient with anti neurofascin 155 (NF155) was 23.22 m/s, the latency of F wave was 62.9-70.7 ms, and the occurrence rate was 85%-95%. The proportion of brachial plexus and lumbar plexus thickening in CMT1A was 83.3% (5/6) and 85.7% (6/7), respectively. The proportion of brachial plexus and lumbar plexus thickening in the CIDP patients was only 25.0% (1/4, 2/8). The nerve roots of brachial plexus and lumbar plexus were significantly thickened in a patient with anti NF155 antibody. CONCLUSION The prolonged latency of F wave in patients with CMT1A reflects the homogenous changes in both proximal and distal peripheral nerves, which can be used as a method to differentiate the CIDP patients characterized by focal demyelinating pathology. Moreover, attention should be paid to differentiate it from the peripheral neuropathy caused by anti NF155 CIDP. Although F wave is often used as an indicator of proximal nerve injury, motor neuron excitability, anterior horn cells, and motor nerve myelin sheath lesions can affect its latency and occurrence rate. F wave abnormalities need to be comprehensively analyzed in combination with the etiology, other electrophysiological results, and MRI imaging.
Humans ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/pathology* ; Median Nerve/pathology* ; Ulnar Nerve/pathology* ; Brachial Plexus/pathology* ; Magnetic Resonance Imaging/methods*