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Objective:To investigate the clinical characteristics of patients with combined oxidative phosphorylation deficiency type 4 (COXPD4) related to TUFM gene variation, in order to improve clinicians′ understanding of the disease. Methods:A case of COXPD4 with cystic leukodystrophy admitted to the Children′s Hospital of Zhengzhou University in June 2021 was taken as the study subject, and her clinical characteristics and genetic testing results were retrospectively analyzed. The "combined oxidative phosphorylation deficiency type 4" " TUFM gene" "cystic leukodystrophy" "combined oxidative phosphorylation deficiency 4" "COXPD 4" " TUFM" and "cystic leukodystrophy" were used as keywords, and the documents on COXPD4 related to TUFM gene mutations were reviewed from Wanfang Data Knowledge Service Platform, CNKI, PubMed Document Database, and National Center for Biotechnology Information (NCBI) until August 2021. The COXPD4 patients that have been reported internationally were analyzed for clinical features and variant types. Results:The patient was a 2-month-old girl with clinical manifestations of delayed development and progressive aggravation, elevated lactic acid in serum and cerebrospinal fluid, and diffuse white matter dysplasia with multiple cystic lesions in cerebral magnetic resonance imaging (MRI). Whole exome sequencing showed TUFM gene complex heterozygous variants c.684_684+4delGGTGA and c.1105C>T, which had not been reported in the past. A total of 5 cases of COXPD4 were reported in 4 English literatures. Together with 1 case in this study, there were 4 cases with detailed clinical history data, including 1 male and 3 females. The clinical manifestations were severe early-onset lactic acidosis and developmental lag, and 3 cases were accompanied by progressive infantile encephalopathy. Among them, 3 cases underwent head MRI examination, all of which showed diffuse white matter signal with multiple cystic lesions, 2 cases with basal ganglia involvement and multiple cerebellar gyri deformity. Genetic test indicated different types of TUFM gene variation. Conclusions:COXPD4 is a rare hereditary mitochondrial disease. For cases with COXPD4 clinical and imaging features, TUFM gene mutations can be screened first.
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Objective:To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome, so as to improve the clinical understanding of the disease.Methods:A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively. The clinical data, laboratory examination, imaging characteristics and gene variation characteristics of the child were summarized.Results:The patient was a 17 months old girl, with the main complaint of "intermittent convulsion with 17 months of underdevelopment". The clinical manifestations were epileptic seizures, which were in the form of a series of spastic seizures, absence seizures, focal seizures, and depigmentation spots can be seen in the trunk and neck. Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres, multiple small nodular shadows under the ependyma of the bilateral lateral ventricles, the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion, and the abdomen color Doppler ultrasound showed polycystic kidney. Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye. The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene (NM_000548) at chromosome position chr16: 2125799-2185690. The real-time quantitative detection system verified that exons 23-42 were deleted, and all exons of PKD1 gene were deleted (NM_001009944), and multiple ligation dependent probe amplification verified that exons 1-46 were deleted, and no downstream gene deletion was found. The overall deletion size was about 60 kb. Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions:TSC2/PKD1 adjacency gene syndrome is relatively rare. It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease. Most of the nervous system and kidney are seriously affected, and the prognosis is poor. TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.
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Objective:To analyze the clinical and imaging characteristics of acute necrotic encephalopathy (ANE) in a child with human herpesvirus-6 (HHV-6) infection.Methods:Retrospective analysis was performed on the clinical data and imaging features of a case of HHV-6 related ANE from Children′s Hospital Affiliated to Zhengzhou University in March 2019.Results:The one year and seven month-old child had acute encephalopathy, recurrent convulsions, consciousness disorders, elevated serum transaminase. The number of cerebrospinal fluid (CSF) cells was normal and the protein increased. High throughput gene testing of CSF showed HHV-6. Cranial magnetic resonance imaging showed multiple symmetry damage in the bilateral thalamus, brainstem, and cerebellum. The symptoms improved after the treatment of glucocorticoids, intravenous immunoglobulin, and plasmapheresis.Conclusions:ANE is a rare severe encephalopathy, the characteristic imaging change of which is symmetry multifocal cerebral damage, especially in the bilateral thalamus. ANE should be considered for patients with frequent convulsions and disturbance of consciousness after virus infection.
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Objective:To investigate the clinical phenotypes, therapy and genetic features of aldehyde dehydrogenase 7 family member A1 (ALDH7A1) gene mutations in five cases of pyridoxine dependent epilepsy (PDE) with diagnosis confirmed by next generation sequencing.Methods:Retrospective analysis was carried out on clinical data of five cases of PDE children with early epilepsy onset who were treated in the Department of Neurology of Children′s Hospital Affiliated to Zhengzhou University from February 2018 to November 2019. Next generation sequencing approach was used for genetic sequencing of proband ALDH7A1 gene and the first generation Sanger was used for validation of family members. And the characteristics of gene mutations were analyzed.Results:Among the five children diagnosed with PDE, the male to female ratio was 4 ∶ 1 and ages at clinic visit ranged from two months to 10 months old. In clinical phenotypes, all five cases experienced onset in neonatal period, with repeated seizures, manifested as myoclonus, spasms or focal paroxysm. The administration of antiepileptic drugs performed poorly in seizure control while long term oral intake of large dose pyridoxine showed better efficacy. All the five cases of children came from compound heterozygous mutations of father and mother, i.e. slicing homozygous mutation c.247-2(IVS2)A>T, missense mutation c.584A>G (p.N195S) and nonsense mutation c.1003C>T(p.R335 *), missense mutation c.1553G>C(p.R518T) and c.1547A>G(p.Y516C), missense mutation c.1547A>G(p.Y516C) and frameshift mutation c.1566_1568delTAC, missense mutation c.1061A>G(p.Y354C) and nonsense mutation c.841C>T(p.Q281X, 259), among which c.247-2(IVS2)A>T was novel splicing site mutation not reported before. Conclusions:PDE is induced by ALDH7A gene mutation. Early clinical manifestations are mostly onset of refractory epilepsy in neonatal period. Antiepileptic drugs perform poorly in terms of efficacy while pyridoxine can control seizure effectively. Gene analysis should be conducted on such patients for confirmed diagnosis.
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Objective:To investigate the clinical characteristics and gene mutation of seven cases of CDKL5 gene related early-onset epileptic encephalopathy diagnosed by next-generation sequencing.Methods:The clinical data of children with early-onset epileptic encephalopathy from February 2018 to December 2019 in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University were retrospectively analyzed. The whole exome sequencing method was used to analyze the entire exome of the proband, and seven cases of CDKL5 gene mutation positive were screened out, and Sanger sequencing verification on family members was performed to identify the source and the characteristics of gene mutations were analyzed.Results:Among the seven children diagnosed with CDKL5 gene related early-onset epileptic encephalopathy, the ratio of male to female was 2∶5, and the age of onset was 15 days to five months of birth. The clinical phenotypes all included different degrees of developmental delay and repeated seizures, which were manifested as general seizures, myoclonic seizures, convulsive seizures or focal seizures; the outcome of use of antiepileptic drugs to control seizures was poor, and some applications of ketogenic diet had better effects. CDKL5 gene mutation sites were all denovo mutations, including NM_003159: c.772_776del (p.K258Efs *10) frameshift mutation, NM_003159.2 (exon: 9-15) heterozygous deletion, CDKL5 hemizygous deletion, NM_003159: c.268 (exon5) G>T (p.E90 *, 941) and NM_003159: c.2578C>T (p.Q860 *, 171) nonsense mutation, NM_003159: c.211A>G (p.Asn71Asp) and NM_001323289: c.545T>C (p.L182P) missense mutation. Among them, c.772_776del (p.K258Efs *10), c.268 (exon5)G>T and c.2578C>T (p.Q860 *, 171) have not been reported. Conclusions:CDKL5 gene related early-onset epileptic encephalopathy is an early onset epilepsy, which is more common in women, and has different forms of seizures. The early electroencephalogram is characterized as severe abnormal brain discharge, and the disease progresses in various forms. There are no specific changes in head magnetic resonance imaging. Different gene mutation sites may lead to different phenotypes and prognostic differences. Many anti-epileptic treatments are ineffective, and ketogenic diets are effective for some patients.
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Objective:To summarize the clinical features and genetic etiology of tuberous sclerosis (TSC).Methods:A retrospective analysis was carried out to identify the clinical features and auxiliary examination reults of TSC patients in 2 pedigrees admitted to our hospital from January 2018 to April 2018. Whole exome sequencing was performed in peripheral blood samples from these patients and the mutations in their parents were validated by Sanger sequencing.Results:The two probands were a one-year and 7-month old girl and a 2-year and 4-month old boy. They were all normal at birth and had epileptic seizures at preschool age. The elder sister, younger sister and mother of the probands showed abnormal skin and no seizures, and the father had normal phenotype. Physical examination showed normal mental and motor development, facial angiofibroma and depigmentation spots on the skin, knots and shark-like spots on part of the skin, and multiple intracranial calcification shadows on head CT; MR imaging revealed multiple abnormal signals under the parenchymal cortex and bilateral lateral ventricles. The proband (1) and her sister carried heterozygous missense mutation c.5024 c >T(p.pro1675leu) in TSC2 gene; ultrasound of heart, liver and kidney showed presence of hamartoma and cystic scotoma in renal parenchyma. The proband (2) and his younger sister carried heterozygosous splicing variation c. 737+1(IVS8)G>A in TSC1 gene, inherited from his mother; the head CT of younger sister was normal, and there was no hamartoma in the younger sister and the mother's internal organs. Conclusions:TSC is characterized by epileptic seizures and abnormal skin changes in preschool age. It may involve multiple hamartomas of skull, heart, liver, kidney, or other internal organs. The mutation frequency of TSC2 gene is higher than that of TSC1 gene, and the clinical phenotype is severe.
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Objective To explore the experiment of Mg2+on effects of cell apoptosis of rabbit secondary brain injury. Methods Fifty New Zealand white rabbits, irrespective of genders were selected, they were randomly divided into ex-perimental group, control group and operation control group, 20 rats in each group of the experimental group and the control group, 10 rabbits were in the sham operation group; animal were used magnesium sulfate after brain injury in the early vein,through the pathology examination of brain tissue around contusion foci, X-ray examination of electron microscopy and cell apoptosis detection, the effect of magnesium ion on the cell apoptosis in secondary brain damage was analyzed. Results The control group after 6 h of brain injury, pathology showed focus of the lesions appeared haem-orrhage, the organization gap widened, peripheral edema, 48 h after brain injury was most significant, the lesions ap-peared cell membrane structure complete, the nucleus pycnosised nerve cells,that was to say, neural cell apoptosis, apoptotic cells were relatively dense; Neural cell degeneration and necrosis of experimental group were less , brain edema was lighter, there were no significant differences on both sides of the lesions; the expression of TUNEL positive cells in normal brain tissue was less, 6-hour-injury specimens appeared TUNEL powder in a small number of positive cells, the number of TUNEL positive cells of specimens of two groups increased with the prolongation of injury time, the peak period was 24 hours, TUNEL positive cells at different stages in the experimental group were significantly lower than those of the control group at the same time segment, the difference had statistical significance (P<0.05). Conclusion Magnesium ions can reduce the number of nerve cell apoptosis of rabbit secondary brain injury, play a pro-tective role in injury of cerebral nerve cells.
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Objective To explore the diagnosis value of CT in subarachnoid hemorrhage(SAH) induced by aneurysm rupture.Methods The clinical and CT data of 119 patients with SAH induced by aneurysm rupture were analyzed respectively.Results The CT characteristic of SAH induced by aneurysm rupture was full of hyperderse in sulcus and schizenceplay,or accompaning intracerebral hematoma in the straight gyrus of frontal lobe and the hippocampal gyrus of parietal lobe.Conclusion The CT has important value for diagnosing SAH induced by aneurysm rupture in the location and the nature.But it is indispensable that the CTA or DSA must be done for ascertaining the artery of responsibility of rupturing aneurysm.
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Objective To evaluate the effect of minimally invasive therapy for treating intraventricular hemorrhage.Methods The minimally invasive therapy with unilateral or bilateral drainage were received according to quantity and shape of intraventricular hemorrhage.Results It was operated 22 cases with unilateral drainage and 28 cases with bilateral drainage in the 50 cases intraventricular hemorrhage.Death was 3 cases and mortality rate was 6% in the minimally invasive therapy.ADL1 15 cases(30%),ADL2 18 CRSeS(36%),ADL3 8 cases(16%),ADLA4 cases(8%),ADL5 2 cases(4%)in leave hospital.Conclusion Minimal invasive therapy of intraventrieular hemorrhage has great superiority,such as it can operate simple,trauma mild,decrease complications and enhance curative effect.It can generalize in the basic hospital.
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Objective - To analyze the relation between classes and prognosis of the brain.stem hemorrhage.Methods 37 patients with spontaneous brainstem hemorrhage were divided into three groups according to con-sciousness and breathing function: Ⅰ group 13 cases with consciousness; Ⅱ group 11 cases without consciousness; Ⅲgroup 13 cases without consciousness and respiration, according to the classes, using different ways and means. Re-suits Ⅰ group 13 cases survival in 13 cases; Ⅱ group 10 cases survival and 1 case death in 11 cases; Ⅲ group 1 case survival and 12 cases death in 13 eases. Conclusion The classes of the brain.stem hemorrhage is propitious to select therapeutic measure and prognostic estimate. The intensive care and the surgery can reduce mortality rate.
