Phenotypic and genotypic characterization of Chinese children diagnosed with tuberous sclerosis complex.

We investigated the clinical phenotypes and genetic mutations in Chinese children diagnosed with tuberous sclerosis complex (TSC). Sequencing of TSC1 and TSC2 genes was performed in 117 children with TSC and their parents. Association of TSC gene mutations with clinical manifestations was investigated. All gene mutations were heterozygous including in 16 patients (13.7%) with mutations in TSC1 gene and 101 patients (86.3%) with mutations in TSC2 gene. Among the 16 patients with TSC1 gene mutations, 15 different types of mutations were found, which included 5 novel mutations; all patients had skin manifestations and epilepsy. Among the 101 patients with TSC2 mutations, 85 different types of mutations were found, which included 25 novel mutations; 97 patients (96.0%) had skin manifestations; 97 (96.0%) had epilepsy; 74 (73.3%) had intellectual disability and 25 patients (24.8%) were autistic. The clinical phenotype of the 14 children with familial TSC was more severe than that of their parents.

[Clinical characteristics and ketogenic diet therapy of glucose transporter type 1 deficiency syndrome in children: a multicenter clinical study].

Objective: To explore the clinical characteristics of pediatric glucose transporter type 1 deficiency syndrome (GLUT1 DS), evaluate the efficacy and safety of ketogenic diet therapy (KDT). Methods: Clinical data of 19 children with GLUT1 DS admitted to Children's Hospital of Fudan University, Tianjin Children's Hospital, Shenzhen Children's Hospital, Children's Hospital of Nanjing Medical University and Jiangxi Provincial Children's Hospital between 2015 and 2019 were collected retrospectively. The first onset symptom, main clinical manifestations, cerebrospinal fluid features and genetic testing results of patients were summarized, the efficacy and safety of ketogenic diet treatment were analyzed. Results: Among the 19 cases, 13 were males and 6 females. The age of onset was 11.0 (1.5-45.0) months,the age of diagnosis was 54.0 (2.8-132.0) months. Epilepsy was the first onset symptom of 13 cases. Different forms of tonic-clonic seizures were the most common types of epilepsy (7 cases with generalized tonic-clonic seizures, 5 cases with focal tonic or clonic seizures, 4 cases with generalized tonic seizures). Antiepileptic drugs were effective in 4 cases. Paroxysmal motor dysfunction was present in 12 cases and ataxia was the most common one. All patients had different degrees of psychomotor retardation. Among 17 patients received cerebrospinal fluid examination, cerebrospinal fluid (CSF) glucose level was lower than 2.2 mmol/L and CSF glucose/glycemic index was<0.45 in 16 cases, only 1 case presented normal CSF glucose level (2.3 mmol/L) and normal CSF glucose/glycemic index(0.47). SLC2A1 gene mutations were found in 16 patients, missense, frameshift and nonsense mutations were the common types with 5 cases, 5 cases and 3 cases respectively. All 19 patients were treated with ketogenic diet, which was effective in 18 cases in seizure control, 11 cases in dyskinesia improvement and 18 cases in cognitive function improvement. No serious side effects were reported in any stage of KDT. Conclusions: The diagnosis of GLUT1 DS is often late. It is necessary to improve the early recognition of the disease and perform CSF glucose detection and genetic testing as early as possible. The KDT is an effective and safe treatment for GLUT1 DS, but a small number of patients have not response to diet therapy.