[Clinical manifestations and neuroradiological findings of CARASIL with a novel mutation]

A 44-year-old female was referred to our department for the evaluation of diffuse leukoencephalopathy. She had exhibited lumbago and gait disturbance due to lumbar spondylosis in the third decade of her life. She had become bed-ridden at 42 of age. Besides, she had developed with cognitive decline and decreased speech in her early forties. Consanguinity was recognized in her family pedigree, such that her father and her maternal grandmother were cousins. One of her elder brothers was found to have developed similar neurological abnormalities. She had never been hypertensive. Blood and cerebrospinal fluid examinations were negative. Cranial MRI revealed extensive white matter lesions, but there were no abnormal findings in her MRA. Locally decreased cerebral blood flow was revealed by cranial SPECT. Despite the lack of alopecia, we considered the diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Her DNA analysis disclosed a novel mutation (c.G821A, p.R274Q) with homozygosity, also identified in the affected elder brother. The in vitro assay for TGFβ repressor activity of HTRA1 implied that the appearance of CARASIL-associated alopecia was independent of TGFβ repressor activity. Longitudinally performed MR spectroscopy showed that her leukoenceplopathy was characterized by early demyelination and intact axonal integrity.