[Clinical and genetic spectrum of 6 cases with asparagine synthetase deficiency].

Objective: To explore the clinical and genetic characteristics of asparagine synthase deficiency. Methods: Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed. Results: All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor. Conclusions: Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

[Clinical and genetic spectrum of SCN2A gene associated epilepsy and episodic ataxia].

Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.

[Clinical effects of surgical treatment of high myopic strabismus fixus by modified Yokoyama's surgery combined with medial rectus muscle recession].

Objective: To analyze clinical effects of modified Yokoyama's surgery combined with medial rectus muscle recession for treatment of high myopic strabismus fixus. Methods: Retrospective analysis of records of 9 patients (14 eyes) with high myopic strabismus fixus treated from February 2013 to December 2016 in the Department of Ophthalmology, Xiangya Hospital, Central South University. All patients underwent modified Yokoyama's surgery. The temporal 1/2 of the superior rectus (SR) and the superior 1/2 of the lateral rectus (LR) were united 12 to 14 mm, combined with medial rectus muscle recession. The angle of deviation of primary position, the mobility of the affected eye, and the change of CT imaging were observed and analyzed before and 6 months after surgery. Statistical analysis was performed by Mann-Whitney U test. Results: The patients were 5 females and 4 males with an average age of (60±10) years. The duration of high myopia was (33.33±6.61) years. The refractive power was (-23.32±5.95) D, and the axial length was (33.04±2.63) mm. The recession mount of medial rectus was (7.2±2.1) mm (4.0-10.0 mm) intraoperatively. At 6 months, the median esotropia improved from 130 (80-140) prism diopter (PD) to 0 (0-10) PD, and the hypotropia from 20 (15-25) PD to 0 (0-5) PD. The median abduction limitation decreased from -3 (-4--1) to -1 (-2-0), and the median limitation of elevation decreased from -2 (-4--1) to 0 (-1-0). The angle of esotropia and hypotropia significantly improved (Z=-2.67, -2.70; P=0.008, 0.007), and the restriction of abduction and elevation decreased (Z=-3.35, -3.24; both P=0.001). Only 3 patients' CT images were enrolled in a comparative study. Preoperative orbital CT scans showed inferior LR displacement and medial SR displacement with the posterior portion of the eyeball to the superotemporal quadrant of the orbit. After surgery, the mean reduction ratio of dislocation degree of the 3 patients was 28.97%, the dislocation of LR and SR was reduced, and the posterior global part was correctly positioned within the orbit. Conclusions: The modified Yokoyama's surgery combined with medial rectus muscle recession can effectively correct high myopic strabismus fixus, recover the eyeball anatomical position, and evidently improve eye mobility. The clinical effects are satisfactory. (Chin J Ophthalmol, 2019, 55: 670-676).