Clinical, Biochemical, Radiological, and Genetic Profile of Patients with Homocysteine Remethylation Pathway Defect and Spastic Paraplegia.
Ann Indian Acad Neurol
; 24(6): 908-916, 2021.
Article
in En
| MEDLINE
| ID: mdl-35359558
ABSTRACT
Objectives:
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.Methods:
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.Results:
A total of seven patients (M F = 52) 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 MTHFR 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.Conclusion:
Evaluation of serum homocysteine and blood methionine in adolescents presenting with progressive spastic paraparesis gives clue to a treatable homocysteine remethylation disorders.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Observational_studies
Language:
En
Journal:
Ann Indian Acad Neurol
Year:
2021
Document type:
Article
Affiliation country:
India