Abstract 38: New Mutations Linked to Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy in Africa and North America

Abstract

Introduction: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare hereditary disease. It is linked to mutations in the high-temperature requirement A serine peptidase 1 gene ( HTRA1 ). The clinical presentation is characterized by cerebral small vessel disease, alopecia, and spondylosis. CARASIL was initially thought to be a recessive disorder and exclusively exist in Asian populations. The paradigm of CARASIL has recently expanded. Genetically confirmed heterozygous mutations and manifestation in other ethnicities were reported. A few cases were reported in Hispanic and Caucasian populations but none in the African population. Here we report a new homozygous mutation in a Hispanic male and a known heterozygous mutation in an African female. Methods: Patients underwent routine ischemic stroke work up and risk factor management. MRI brain results were consistent with severe small vessel disease out of proportion to age. Genetic testing for vascular dementia for NOTCH-3 and HTRA1 in Patient 1 and only HTRA1 in Patient 2 were performed through Mayo Clinic. Results: Table 1. Patient Characteristics and HTRA1 Mutations Discussion: The prevalence of CARASIL is unknown but probably underestimated. Since the recognition of heterozygous HTRA1 mutation in CARASIL, more cases of heterozygous HTRA1 mutations have been reported. One of the clinical CARASIL triad -alopecia was not reported or observed in our cases. Cases of CARASIL without alopecia have been reported. Thus, CARASIL should still be suspected in the appropriate clinical presentation even if there is no classic triad or in non-Asian populations. Our cases expanded CARASIL mutations and affected populations. Being more aware of the broad clinical presentation of CARASIL can lead to early diagnosis.