{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:21:47Z","timestamp":1787757707634,"version":"build-2784847793"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11]]},"abstract":"\n Objectives:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n This was a retrospective study conducted by reviewing the medical records of patients with serum homocysteine levels >50 \u03bcmol\/L between January 2015 and January 2019 at our hospital. We included patients presenting with progressive spastic paraparesis, having serum homocysteine >50 \u03bcmol\/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.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n 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 \u00b1 2.4 years (range: 9\u201317 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 \u03bcmol\/L) was noted in 6\/7 (85.7%) patients with median levels of serum homocysteine being 185.7 \u03bcmol\/L (range: 85.78\u2013338.5 \u03bcmol\/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\n MTHFR<\/jats:italic>\n 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 \u03bcmol\/L.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Evaluation of serum homocysteine and blood methionine in adolescents presenting with progressive spastic paraparesis gives clue to a treatable homocysteine remethylation disorders.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/aian.aian_223_21","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T11:52:58Z","timestamp":1639482778000},"page":"908-916","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Clinical, Biochemical, Radiological, and Genetic Profile of Patients with Homocysteine Remethylation Pathway Defect and Spastic Paraplegia"],"prefix":"10.4103","volume":"24","author":[{"given":"Hansashree","family":"Padmanabha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Mahale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Christopher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautham","family":"Arunachal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahammad Samim","family":"Mondal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram 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