Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.
Malignant struma ovarii is a very rare disease and, therefore, there is neither common agreement on treatment regimens nor sufficient follow-up experience. We present a case of a 49-year-old woman with malignant struma ovarii of the follicular type, who received ablative radioiodine treatment after thyroidectomy and surgical removal of the primary tumour. During follow-up examinations an increasing thyroglobulin level was found, caused by a tumour relapse with suspected urinary bladder infiltration on CT and proven uptake of radioiodine on whole-body scanning with iodine-131. After administration of 6GBq 131I, complete tumour regression was achieved with no evidence of a new relapse during a 30-month follow-up period. Correspondingly, repeated thyroglobulin measurements were all negative. This case demonstrates the benefit of combined surgical and radioiodine treatment of malignant struma ovarii for both monitoring and therapy of relapse or metastases; thus, the same therapeutic regimen as is employed in primary differentiated thyroid carcinoma may be recommended.
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