Sodium valproate, a potential repurposed treatment for the neurodegeneration in Wolfram syndrome (TREATWOLFRAM): trial protocol for a pivotal multicentre, randomised double-blind controlled trial.

Introduction: Wolfram syndrome (Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via alteration of cell cycle kinetics, increases in p21 expression levels and reduction in apoptosis and increase in Wolframin protein expression.

-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation.

Heterozygous mutations in are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although -related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease.

Biallelic variants lead to a neurodevelopmental phenotype with gradual neurological impairment.

Biallelic variants in NADH (nicotinamide adenine dinucleotide (NAD) + hydrogen (H))-ubiquinone oxidoreductase 1 alpha subcomplex 13 have been linked to mitochondrial complex I deficiency, nuclear type 28, based on three affected individuals from two families. With only two families reported, the clinical and molecular spectrum of NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13related diseases remains unclear. We report 10 additional affected individuals from nine independent families, identifying four missense variants (including recurrent c.

Disorder of intracellular cobalamin metabolism: Importance of rapid diagnostic illustrated by a case report of early-onset methylmalonic aciduria and homocystinuria, cobalamin C type.

Methylmalonic aciduria and homocystinuria, cobalamin C type (cblC), constitute the most common inborn error of intracellular cobalamin metabolism. Here, we report the case of a 6-month-old child, presenting severe subacute neurological decline associated with failure to thrive. Biochemical tests indicated a disorder of intracellular cobalamin metabolism, with elevated urinary and plasma methylmalonic acid levels associated with high plasma homocysteine concentrations, with normal plasma vitamin B12 concentrations.