A straightforward method for quantification of vinyl functionalized water soluble alginates via 13C-NMR spectroscopy.

Alginates are fairly abundant in nature and possess many interesting properties, including their biocompatibility and ability to absorb large amounts of water. Hence, increasing interest in their derivatization has been observed and the determination of the number of newly introduced functionalities has become a key issue. For this purpose, literature generally reports on conventional 1H-NMR spectra, typically recorded at elevated temperatures and/or after hydrolysis of the alginate to circumvent line broadening effects resulting from the high viscosity. The present work reports on the modification of alginate with methacrylate functionalities and determination of the resulting degree of substitution (DS), i.e. the number of introduced methacrylate moieties relative to the initial amount of hydroxyl groups along the alginate backbone, via NMR spectroscopy. Freeze-drying and low power water presaturation were applied to improve the quality of the 1H NMR spectra. Nevertheless, it remains a qualitative method, to be used only for mutual comparisons of samples. A new and accurate method for DS determination of methacrylated alginates, based on 13C-NMR spectroscopy, is proposed. Quantitative 13C-NMR spectra were recorded with reduced measuring times by addition of a paramagnetic relaxation agent. The proposed method will also be applicable for other water-soluble functionalized alginates and polysaccharides in general.

GJA1 Variants Cause Spastic Paraplegia Associated with Cerebral Hypomyelination.

Oculodentodigital dysplasia is an autosomal dominant disorder due to GJA1 variants characterized by dysmorphic features. Neurologic symptoms have been described in some patients but without a clear neuroimaging pattern. To understand the pathophysiology underlying neurologic deficits in oculodentodigital dysplasia, we studied 8 consecutive patients presenting with hereditary spastic paraplegia due to GJA1 variants. Clinical disease severity was highly variable. Cerebral MR imaging revealed variable white matter abnormalities, consistent with a hypomyelination pattern, and bilateral hypointense signal of the basal ganglia on T2-weighted images and/or magnetic susceptibility sequences, as seen in neurodegeneration with brain iron accumulation diseases. Patients with the more prominent basal ganglia abnormalities were the most disabled ones. This study suggests that GJA1-related hereditary spastic paraplegia is a complex neurodegenerative disease affecting both the myelin and the basal ganglia. GJA1 variants should be considered in patients with hereditary spastic paraplegia presenting with brain hypomyelination, especially if associated with neurodegeneration and a brain iron accumulation pattern.