Padmanabha Hansashree, Mahale Rohan, Christopher Rita, Arunachal Gautham, Bhat Maya, Mondal Mahammad Samim, Anjanappa Ram Murthy, Mundlamuri Ravindranadh Chowdhary, Yadav Ravi, Vengalil Seena, Mailankody Pooja, Mathuranath Pavagada S, Chandra Sadanandavalli R, Nalini Atchayaram
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.
Ann Indian Acad Neurol. 2021 Nov-Dec;24(6):908-916. doi: 10.4103/aian.AIAN_223_21. Epub 2021 Dec 14.
The objective of this study is to describe the clinical, biochemical, radiological, and genetic profile of patients presenting with progressive spastic paraparesis due to homocysteine remethylation pathway defect.
This was a retrospective study conducted by reviewing the medical records of patients with serum homocysteine levels >50 μmol/L between January 2015 and January 2019 at our hospital. We included patients presenting with progressive spastic paraparesis, having serum homocysteine >50 μmol/L with low or normal blood methionine suggesting disorders of homocysteine remethylation. Demographic details, clinical manifestations, biochemical abnormalities, neuroimaging findings, and genetic profile were analyzed.
A total of seven patients (M: F = 5:2) fulfilled the study eligibility criteria. The mean age at onset of the disease was 13.4 ± 2.4 years (range: 9-17 years). Spastic paraparesis was the presenting manifestation in 4/7 (57.1%) patients. Other manifestations included cognitive decline, poor scholastic performance, behavioral disturbances, seizures, and spastic bladder. Severe hyperhomocysteinemia (>100 μmol/L) was noted in 6/7 (85.7%) patients with median levels of serum homocysteine being 185.7 μmol/L (range: 85.78-338.5 μmol/L). Neuroimaging showed parieto-occipital predominant leukoencephalopathy in 5/7 (71.4%) and diffuse cerebral atrophy in 1/7 (14.2%). Genetic analysis in three patients revealed pathogenic missense variants c.459C >G (p.Ile153Met), c.973C >T (p.Arg325Cys), and c.1031G >T (p.Arg344Met) in gene. All the patients received vitamin B12 (injection and oral), folic acid, and pyridoxine and two patients received betaine. At the last follow-up of a median duration of 12 months, there was a good clinical and biochemical response with reduction in the median value of serum homocysteine by 77.5 μmol/L.
Evaluation of serum homocysteine and blood methionine in adolescents presenting with progressive spastic paraparesis gives clue to a treatable homocysteine remethylation disorders.
本研究的目的是描述因同型半胱氨酸再甲基化途径缺陷而出现进行性痉挛性截瘫患者的临床、生化、放射学和基因特征。
这是一项回顾性研究，通过查阅我院2015年1月至2019年1月期间血清同型半胱氨酸水平>50μmol/L患者的病历进行。我们纳入了表现为进行性痉挛性截瘫、血清同型半胱氨酸>50μmol/L且血蛋氨酸水平低或正常提示同型半胱氨酸再甲基化障碍的患者。分析了人口统计学细节、临床表现、生化异常、神经影像学发现和基因特征。
共有7名患者（男:女=5:2）符合研究纳入标准。疾病发病的平均年龄为13.4±2.4岁（范围：9 - 17岁）。痉挛性截瘫是4/7（57.1%）患者的首发表现。其他表现包括认知下降、学业成绩差、行为障碍、癫痫发作和痉挛性膀胱。6/7（85.7%）患者存在严重高同型半胱氨酸血症（>100μmol/L），血清同型半胱氨酸中位数水平为185.7μmol/L（范围：85.78 - 338.5μmol/L）。神经影像学显示5/7（71.4%）患者以顶枕叶为主的白质脑病，1/7（14.2%）患者存在弥漫性脑萎缩。对3名患者的基因分析揭示了该基因中致病性错义变异c.459C>G（p.Ile153Met）、c.973C>T（p.Arg325Cys）和c.1031G>T（p.Arg344Met）。所有患者均接受了维生素B12（注射和口服）、叶酸和吡哆醇治疗，2名患者接受了甜菜碱治疗。在中位随访时间为12个月的最后一次随访时，临床和生化方面有良好反应，血清同型半胱氨酸中位数降低了77.5μmol/L。
对出现进行性痉挛性截瘫的青少年进行血清同型半胱氨酸和血蛋氨酸评估可为可治疗的同型半胱氨酸再甲基化障碍提供线索。
