Diagnosis and treatment recommendations for glucose transporter 1 deficiency syndrome.

Background: Glucose transporter 1 deficiency syndrome (Glut1DS) was initially reported by De Vivo and colleagues in 1991. This disease arises from mutations in the SLC2A1 and presents with a broad clinical spectrum. It is a treatable neuro-metabolic condition, where prompt diagnosis and initiation of ketogenic dietary therapy can markedly enhance the prognosis.

Novel CAD gene mutations in a boy with developmental and epileptic encephalopathy 50 with dramatic response to uridine therapy: a case report and a review of the literature.

Background: Developmental and epileptic encephalopathy-50 (DEE-50) is a rare clinical condition believed to be caused by a mutation in the CAD gene and is associated with a bleak prognosis. CAD-related diseases have a wide range of clinical manifestations and other symptoms that may be easily overlooked. Like other rare diseases, the clinical manifestations and the treatment of DEE-50 necessitate further investigation.

CAG Repeat Expansion in THAP11 Is Associated with a Novel Spinocerebellar Ataxia.

Background: More than 50 loci are associated with spinocerebellar ataxia (SCA), and the most frequent subtypes share nucleotide repeats expansion, especially CAG expansion.

Objective: The objective of this study was to confirm a novel SCA subtype caused by CAG expansion.

Methods: We performed long-read whole-genome sequencing combined with linkage analysis in a five-generation Chinese family, and the finding was validated in another pedigree.

MECP2 germline mosaicism plays an important part in the inheritance of Rett syndrome: a study of MECP2 germline mosaicism in males.

Background: Germline mosaicisms could be inherited to offspring, which considered as "de novo" in most cases. Paternal germline MECP2 mosaicism has been reported in fathers of girls with Rett syndrome (RTT) previously. For further study, we focused on MECP2 germline mosaicism in males, not only RTT fathers.

Ultrasound-guided interlaminar approach for nusinersen administration in patients with spinal muscular atrophy with spinal fusion or severe scoliosis.

Background: Intrathecal injection of medications can be challenging in spinal muscular atrophy (SMA) patients with severe scoliosis or after spine surgery. Here we report our experience with real-time ultrasound (US)-guided intrathecal administration of nusinersen in patients with SMA.

Methods: Seven patients (six children and one adult) with either spinal fusion or severe scoliosis were enrolled.

A novel homozygous variant in an infant with hypermanganesemia and a review of the literature.

Background: Manganese (Mn) is an essential trace metal necessary for good health; however, excessive amounts in the body are neurotoxic. To date, three genes (, , and ) have been discovered to cause inborn errors in Mn metabolism in humans. As very rare diseases, the clinical features require further clarification.

Clinical and genetic spectrum of hereditary spastic paraplegia in Chinese children.

Aim: To explore the clinical and genetic spectrum of hereditary spastic paraplegia (HSP) in Chinese children.

Method: This retrospective study was conducted between January 2014 and October 2021 in children clinically diagnosed with either pure HSP (pHSP) or complex HSP (cHSP).

Results: We investigated 45 children (32 males, 13 females; mean age [SD] at symptom onset 4 years [7 months]).

Juvenile Generalized Myasthenia Gravis With AChR and MuSK Antibody Double Positivity: A Case Report With a Review of the Literature.

Myasthenia gravis is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. The presence of both antibodies in the serum of patients with myasthenia gravis has been rarely reported. Case description: A 9-year-old girl was admitted to our hospital with the chief complaints of reduced facial expression for 3 months and unclear speech and choking from drinking water for 2 months.

Genetic analysis and prenatal diagnosis of 76 Chinese families with X-linked adrenoleukodystrophy.

Background: Variants in the ATP binding cassette protein subfamily D member 1 (ABCD1) gene are known to cause X-linked adrenoleukodystrophy (X-ALD). This study focused on the characteristics of ABCD1 variants in Chinese X-ALD families and elucidated the value of genetic approaches for X-ALD.

Methods: 68 male probands diagnosed as X-ALD were screened for ABCD1 variants by the Sanger sequencing of polymerase chain reaction (PCR) products and multiplex ligation-dependent probe amplification (MLPA) combined with long-range PCR.

Mitochondrial DNA Copy Number in Rett Syndrome Caused by Methyl-CpG-Binding Protein-2 Variants.

Objective: To determine changes in mitochondrial DNA (mtDNA) copy number in peripheral blood in Rett syndrome caused by methyl-CpG-binding protein-2 (MECP2) variants and explore the mechanism of mitochondrial dysfunction in Rett syndrome.

Study Design: Female patients who were diagnosed with Rett syndrome and had an MECP2 variant (n = 142) were recruited in this study, along with the same number of age- and sex-matched healthy controls. MtDNA copy number was quantified by real-time quantitative polymerase chain reaction with TaqMan probes.

Report of the Largest Chinese Cohort With Gene Defect and Literature Review.

Thiamine metabolism dysfunction syndrome 2 (THMD2) is a rare metabolic disorder caused by mutations, inherited in autosomal recessive pattern. As a treatable disease, early diagnosis and therapy with vitamin supplementation is important to improve the prognosis. So far, the reported cases were mainly from Saudi Arab regions, and presented with relatively simple clinical course because of the hot spot mutation (T422A).

Genetic analysis of 20 patients with hypomyelinating leukodystrophy by trio-based whole-exome sequencing.

Hypomyelinating leukodystrophies (HLDs) are a rare group of disorders characterized by myelin deficit of the brain-based on MRI. Here, we studied 20 patients with unexplained HLD to uncover their genetic etiology through whole-exome sequencing (WES). Trio-based WES was performed for 20 unresolved HLDs families after genetic tests for the PLP1 duplication and a panel of 115 known leukodystrophy-related genes.

Gene Variants in Eight Chinese Patients With a Wide Range of Phenotypes.

The gene encodes the voltage-dependent P/Q-type calcium channel subunit alpha-1A, which is widely expressed throughout the CNS. The biological roles of the P/Q channel are diverse and the phenotypic spectrum caused by mutations is wide. The aim of this study is to demonstrate its phenotypic diversity and analyze the genotype-phenotype correlations in a cohort of Chinese patients.

MECP2 mutation spectrum and its clinical characteristics in a Chinese cohort.

The dysfunction of methyl-CpG-binding protein 2 (MeCP2) is associated with several neurological disorders, of which Rett syndrome (RTT) is the most prominent. This study focused on a Chinese patient cohort with MECP2 mutations, and analyzed the characteristics of these mutations and their clinical manifestations. In total, 666 patients were identified with 126 different MECP2 mutations, including 22 novel mutations.

The genetic and clinical characteristics of aromatic L-amino acid decarboxylase deficiency in mainland China.

Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare neurotransmitter metabolic disorder caused by DDC gene mutations, which leads to the metabolic disturbance of dopamine and serotonin. Most of the reported cases came from Taiwan China, but patients from mainland China were seldomly reported. The current study was the largest AADCD patient cohort from mainland China.

Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS).

Objective: To summarize and extend the phenotypic characterization of Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome, and to discuss genotype-phenotype correlations.

Methods: Collecting clinical information of 17 patients with pathogenic variants in PIGN, PIGA, and PIGT. Genetic studies were performed on all patients.

Clinical and Genetic Heterogeneity in a Cohort of Chinese Children With Dopa-Responsive Dystonia.

The aim of this study was to investigate the genetic and clinical features of dopa-responsive dystonia (DRD) in China. Characteristics of gene mutations and clinical manifestations of 31 patients diagnosed with DRD were analyzed retrospectively. From January 2000 to January 2019, 31 patients were diagnosed with DRD.

Rett syndrome-causing mutations compromise MeCP2-mediated liquid-liquid phase separation of chromatin.

Rett syndrome (RTT), a severe postnatal neurodevelopmental disorder, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). MeCP2 is a chromatin organizer regulating gene expression. RTT-causing mutations have been shown to affect this function.

A splice site mutation c.1251G>A of ISPD gene is a common cause of congenital muscular dystrophy in Chinese patients.

The predicted synonymous mutation c.1251G>A of ISPD (NM_001101426.3) is a hot spot causing exon 9 skipping in five patients.

Rett and Rett-like syndrome: Expanding the genetic spectrum to KIF1A and GRIN1 gene.

Background: This study aimed to investigate the new genetic etiologies of Rett syndrome (RTT) or Rett-like phenotypes.

Methods: Targeted next-generation sequencing (NGS) was performed on 44 Chinese patients with RTT or Rett-like phenotypes, in whom genetic analysis of MECP2, CDKL5, and FOXG1 was negative.

Results: The detection rate was 31.

Pediatric Autoimmune Encephalitis: Case Series From Two Chinese Tertiary Pediatric Neurology Centers.

We retrospectively analyzed the clinical characteristics of children with autoimmune encephalitis (AE) in two Chinese tertiary pediatric neurology centers. We also compared anti-NMDAR encephalitis with and without co-positive MOG antibody, as well as specific autoantibody-positive AE and autoantibody-negative but probable AE. A retrospective study of children (0-18 years old) with AE in Peking University First Hospital and Children's Hospital Affiliated to Capital Institute of Pediatrics was carried out from May 2012 to January 2017.

Heterogeneous clinical and functional features of GRIN2D-related developmental and epileptic encephalopathy.

N-methyl d-aspartate receptors are ligand-gated ionotropic receptors mediating a slow, calcium-permeable component of excitatory synaptic transmission in the CNS. Variants in genes encoding NMDAR subunits have been associated with a spectrum of neurodevelopmental disorders. Here we report six novel GRIN2D variants and one previously-described disease-associated GRIN2D variant in two patients with developmental and epileptic encephalopathy.