A rare case of a long-lived patient with Canavan syndrome

Giuseppe Liardi , Salvatore Dongiovanni , Michelangelo Carucci , Valentina Andreozzi , Connye Mattera , Federica Quadro , Gennaro Calafiore , Sabrina Gentile , Nicoletta Liardi
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Abstract

This case report describes the clinical case of a patient with Canavan Syndrome, a condition characterized by high mortality in infancy, who reached the age of 32. The article focuses on the patient's medical history, clinical and instrumental evaluations, and the treatment administered, then compares the patient's clinical history with that of other individuals affected by the same disease, and finally assesses the various treatment options and future therapeutic prospects for this condition. Canavan disease is a rare, progressive, autosomal recessive disorder that begins in infancy or early childhood [1,2]. It is caused by genetic mutation in the aspartoacylase (ASPA) gene, which encodes a metabolic enzyme synthesized by oligodendrocytes in the brain. ASPA mutations lead to a deficiency of the enzyme aspartoacylase resulting in accumulation of N-Acetylaspartic acid in the brain. This accumulation will result in oligodendrocyte dysfunction, axonal myelin degeneration and cerebral spongiform changes [3]. Sufficient data is unavailable to calculate the prevalence [4]. The neonatal form is the most common (85–90%) and is usually associated with the most severe symptoms while a less severe atypical Canavan disease (10%-15%) is associated with onset from infancy to adolescence, milder development delay, with or without regression. Typical features of the neonatal form include lethargy, listlessness, weak cry and suck, a lack of head control when the baby is pulled from a lying to a sitting position, hypotonia, poor visual tracking or blindness, vomiting, and seizures. Macrocephaly becomes prominent by the age of three to six months, and hypotonia eventually progresses to spasticity, hyperreflexia, extensor plantar responses, and tonic extensor spasms. It can also be present blindness due to optic atrophy. [5] No consensus clinical diagnostic criteria for Canavan disease have been established. Diagnosis is based on compatible clinical features and neuroimaging findings (spongiform degeneration and edema of the white matter, brain enlargement) associated with elevated levels of urine NAA and, on proton magnetic resonance spectroscopy (1/H-MRS), an increase in NAA, a reduction in Cr and choline, and an increase in lactate levels [6,7]. The molecular diagnosis of Canavan disease is established in a proband with biallelic pathogenic variant in the ASPA gene identified by molecular genetic testing [8]. There is no cure for Canavan disease. Supportive treatment is recommended, in particular to provide adequate hydration and nutrition, managing the risk of infections and protecting the airway [6]. Prognosis is variable, although most people with the neonatal/infantile form die in the first two decades of life. [5]
这是一例罕见的长寿命卡纳万综合症患者
本病例报告描述了一名32岁的卡纳万综合征患者的临床病例,该病的特点是婴儿死亡率高。本文重点介绍了患者的病史、临床和仪器评估以及所给予的治疗,然后将患者的临床病史与患有同一疾病的其他个体的临床病史进行比较,最后评估了该疾病的各种治疗方案和未来治疗前景。卡纳万病是一种罕见的进行性常染色体隐性遗传病,发病于婴儿期或幼儿期[1,2]。它是由天冬氨酸酰化酶(ASPA)基因的基因突变引起的,该基因编码大脑中少突胶质细胞合成的一种代谢酶。ASPA突变导致天冬氨酸酰化酶的缺乏,导致大脑中n -乙酰天冬氨酸的积累。这种积累将导致少突胶质细胞功能障碍,轴突髓鞘变性和脑海绵状改变b[3]。没有足够的数据来计算患病率。新生儿形式是最常见的(85-90%),通常与最严重的症状相关,而不太严重的非典型卡纳万病(10%-15%)与从婴儿期到青春期发病有关,发育延迟较轻,有或无倒退。新生儿形式的典型特征包括嗜睡、无精打采、微弱的哭泣和吸吮、当婴儿从躺姿拉到坐姿时缺乏头部控制、张力低下、视觉追踪不良或失明、呕吐和癫痫发作。大头畸形在3 ~ 6个月时变得突出,张力不足最终发展为痉挛、反射亢进、足底伸肌反应和强直性伸肌痉挛。也可因视神经萎缩而导致失明。[5]对于Canavan病尚未建立一致的临床诊断标准。诊断是基于与尿NAA水平升高相关的临床特征和神经影像学结果(海绵状变性和白质水肿,脑肿大),以及质子磁共振波谱(1/H-MRS), NAA升高,Cr和胆碱降低,乳酸水平升高[6,7]。Canavan病的分子诊断是通过分子基因检测[8]鉴定出ASPA基因双等位致病变异的先证者建立的。卡纳万病无法治愈。推荐支持性治疗,特别是提供充足的水分和营养,控制感染风险和保护气道bbb。虽然大多数新生儿/婴儿形式的人在生命的头20年死亡,但预后是可变的。[5]
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Brain disorders (Amsterdam, Netherlands)
Brain disorders (Amsterdam, Netherlands) Neurology, Clinical Neurology
CiteScore
1.90
自引率
0.00%
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0
审稿时长
51 days
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