Genetic Analysis of , , and in Familial Episodic Pain Syndrome (FEPS) in Japan and Proposal of Clinical Diagnostic Criteria.

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of , , and , which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care.

Clinical features of two Japanese siblings of neuronal ceroid lipofuscinosis type 1 (CLN1) complicated with TypeⅡ diabetes mellitus.

Neuronal ceroid lipofuscinosis type1(CLN1), is a one form of the group of neuronal ceroid lipofuscinoses (NCLs), which is a neurodegenerative disorder characterized by progressive psychomotor deterioration, ataxia, epilepsy, and visual impairment. Neurological manifestations occur at a wide range of ages, from infancy to adulthood, but are most common in infancy. The prevalence of CLN1 is unclear; however, it is very rare in Japan and Europe.

Novel BCL11B truncation variant in a patient with developmental delay, distinctive features, and early craniosynostosis.

Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities (MIM # 618092) is a congenital disorder derived from pathogenic variants of the B-cell leukemia/lymphoma 11B gene (BCL11B). Several variants have been reported to date. Here, through comprehensive genomic analysis, a novel BCL11B truncation variant, NM_138576.

A recurrent de novo ZSWIM6 variant in a Japanese patient with severe neurodevelopmental delay and frequent vomiting.

A recurrent ZSWIM6 variant, NM_020928.2:c.2737C>T [p.

Unexpected elevation in valproic acid concentration and agranulocytosis in a patient with short-chain acyl-CoA dehydrogenase deficiency.

Background: Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive metabolic disorder or condition of fatty acid β-oxidation, caused by mutations in the gene encoding SCAD (ACADS). We report an infant with SCAD deficiency who unexpectedly exhibited an extremely high blood concentration of valproic acid (VPA) and agranulocytosis.

Case Report: An 8-month-old girl was diagnosed with West syndrome (infantile spasms), and VPA was administered at the standard level of 25 mg/kg/day.

Two cases of childhood narcolepsy mimicking epileptic seizures in video-EEG/EMG.

Narcolepsy is characterized by excessive sleepiness, hypnagogic hallucinations, and sleep paralysis, and can occur with or without cataplexy. Here, we report two children with narcolepsy presenting with cataplexy mimicking epileptic seizures as determined by long-term video-electroencephalography (EEG) and electromyography (EMG) monitoring. Case 1 was a 15-year-old girl presenting with recurrent episodes of "convulsions" and loss of consciousness, who was referred to our hospital with a diagnosis of epilepsy showing "convulsions" and "complex partial seizures".

An episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy observed in a patient with a novel frameshift mutation in HNRNPU.

Microdeletions in the 1q44 region encompassing the HNRNPU gene have been associated with infantile spasms and hemiconvulsion-hemiplegia-epilepsy syndrome. Recent studies have revealed that heterozygous HNRNPU variants resulted in early onset epilepsy and severe intellectual disability. A de novo frameshift mutation in HNRNPU was identified in a 5-year-old boy with developmental delay associated with Rett-like features including stereotypic hand movements and respiratory abnormalities with episode of apnea and hyperpnea followed by falling.

The severe clinical phenotype for a heterozygous Fabry female patient correlates to the methylation of non-mutated allele associated with chromosome 10q26 deletion syndrome.

Heterozygous Fabry females usually have an attenuated form of Fabry disease, causing them to be symptomatic; however, in rare cases, they can present with a severe phenotype. In this study, we report on a 37-year-old woman with acroparesthesia, a dysmorphic face, left ventricular hypertrophy, and intellectual disability. Her father had Fabry disease and died due to chronic renal and congestive cardiac failure.

Development of catecholamine and cortisol stress responses in zebrafish.

Both adrenal catecholamines and steroids are known to be involved in the stress response, immune function, blood pressure and energy homeostasis. The response to stress is characterized by the activation of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary system, though the correlation with activation and development is not well understood. We evaluated the stress response of both cortisol and catecholamines during development in zebrafish.

Clinical, biochemical and molecular analysis of 13 Japanese patients with β-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation [corrected].

β-ureidopropionase (βUP) deficiency is an autosomal recessive disease characterized by N-carbamyl-β-amino aciduria. To date, only 16 genetically confirmed patients with βUP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese βUP deficient patients.

Microdeletions of 3p21.31 characterized by developmental delay, distinctive features, elevated serum creatine kinase levels, and white matter involvement.

Interstitial deletions of chromosome 3 are rare, and only one patient with a microdeletion of 3p21.31 has been reported to date. We identified two additional cases of patients with microdeletions of 3p21.

[A child with paroxysmal exertion-induced dyskinesia].

We experienced a 12-year-old boy with paroxysmal exertion (exercise)-induced dyskinesia (PED). His attacks, characterized by painless paralytic stiffness of the extremities during running or playing, developed at 4 years of age. He was initially diagnosed as having epilepsy based on epileptic discharges on interictal EEG.

ß-ureidopropionase deficiency: phenotype, genotype and protein structural consequences in 16 patients.

ß-ureidopropionase is the third enzyme of the pyrimidine degradation pathway and catalyzes the conversion of N-carbamyl-ß-alanine and N-carbamyl-ß-aminoisobutyric acid to ß-alanine and ß-aminoisobutyric acid, ammonia and CO(2). To date, only five genetically confirmed patients with a complete ß-ureidopropionase deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 11 newly identified ß-ureidopropionase deficient patients as well as the analysis of the mutations in a three-dimensional framework.

Role of dual leucine zipper-bearing kinase (DLK/MUK/ZPK) in axonal growth.

In developing cerebral cortices, post-mitotic neurons migrate toward the pial surface, elongating their axons concurrently. It has been reported that targeted-deletion of the dual leucine zipper-bearing kinase (DLK)/mitogen-activated protein kinase upstream protein kinase (MUK)/leucine-zipper protein kinase (ZPK) gene, which encodes a MAP kinase kinase kinase (MAPKKK) for c-Jun N-terminal kinase (JNK), leads to a neuronal migration-defect and hypoplasia of axonal fiber tracts including those of the anterior commissure and corpus callosum. However, there is no evidence that DLK directly regulates axonal development, because another possibility, i.