背景:常染色体隐性遗传性脑动脉病伴皮质下梗死和白质脑病(CARASIL)是一种常染色体隐性遗传性疾病,以秃顶为特征,复发性缺血性卒中,腰痛,头痛,与高温要求丝氨酸肽酶A1(HTRA1)基因的纯合突变密切相关的痴呆。通常认为HTRA1的杂合突变是非致病性的。尽管已经发现只有少数具有杂合突变的患者可以呈现一些表现,他们的临床症状不典型,温和一点,并且总是具有较低的神经外特征。这里,本研究最初报道了1例HTRA1杂合突变的罕见患者,该患者具有CARASIL的所有典型特征以及严重的临床症状和快速进展.病例介绍:一名43岁的女性患者出现逐渐发作的头痛和认知功能下降。随着时间的推移,她的头痛加剧,痴呆症状开始逐渐显现。在她早年的时候,她的头发稀疏,随后在30多岁时发生了两次缺血性中风。此外,她在去我们医院之前也有腰痛和尿潴留的病史。患者的磁共振成像显示存在广泛的白质病变,梗塞,和微出血,除了腰椎间盘突出和退行性病变。观察到的临床特征与CARASIL有很强的相关性,患者被诊断为HTRA1基因中905G>A(Arg302Gln)的杂合错义突变。患者在出院后持续随访超过3年。她做了膀胱造口术,延髓麻痹的症状以渐进的方式发展。目前,运动功能和日常生活活动显著下降,导致个人卧床时间超过1年。结论:本病例提示携带G905A杂合突变的患者也可能具有典型的CARASIL临床特征,这使我们对CARASIL有更全面的了解。
Background: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive disorder characterized by baldness, recurrent ischemic stroke, lumbago, headache, and dementia which is closely related to homozygous mutations of the high-temperature requirement serine peptidase A1 (HTRA1) gene.
Heterozygous mutations of HTRA1 are usually considered to be non-pathogenic. Although it has been revealed that only a few patients with
heterozygous mutations could present some manifestations, their clinical symptoms were atypical, milder, and always with a lower frequency of extra-neurological features. Here, a rare patient with
heterozygous mutation of HTRA1 who had all typical features of CARASIL as well as severe clinical symptoms and rapid progression was initially reported in our study.
Case presentation: A 43-year-old female patient presented with a gradual onset of headache and cognitive decline. As time progressed, her headache intensified and symptoms of dementia began to manifest gradually. During her early years, she had thinning hair and subsequently experienced two occurrences of ischemic strokes in her thirties. Furthermore, she also had a history of lumbago and urinary retention before visiting our hospital. The patient\'s magnetic resonance imaging revealed the presence of widespread white matter lesions, infarctions, and microbleeds, in addition to lumbar disc herniation and degenerative lesions. The observed clinical characteristics had a strong correlation with CARASIL, and the patient was diagnosed with a heterozygous missense mutation of 905G>A (Arg302Gln) in the HTRA1 gene. The patient has been under continuous follow-up for a duration exceeding 3 years subsequent to her release from the hospital. She underwent cystostomy, and symptoms of bulbar paralysis developed in a progressive way. Currently, there has been a notable decrease in motor function and activities of daily living, resulting in the individual being confined to bed for a duration exceeding 1 year. Conclusion: This
case suggests that patients carrying a
heterozygous mutation in G905A may also have typical clinical features of CARASIL, which allows us to have a more comprehensive understanding of CARASIL.