Treatable cause of hereditary spastic paraplegia: eight cases of combined homocysteinaemia with methylmalonic aciduria

AbstractCombined homocysteinemia with methylmalonic aciduria (MMA/HCY) are genetic disorders of intracellular cobalamin (cbl) transport and processing that cause downstream deficiencies in methylcobalamin and adenosylcobalamin. Untreated disease is characterized biochemically by methylmalonic aciduria and hyperhomocysteinemia, while the clinical features are variable. When spastic paraplegia (SP) dominates, it is difficult to differentiate from hereditary spastic paraplegia (HSP). Clinical, biochemical and imaging features were reviewed in eight patients with MMA/HCY that mimicked HSP. Seven males and one female were enrolled. The median onset age was 13  years old (range 7–26 years old). The median time delay of diagnosis was 20.5 months (range 2–60 months). Spastic gait was the first symptom in four patients, while the other four patients presented with chronic emotional abnormalities or cognitive impairment. The main clinical manifestatio n was SP, and other neurological symptoms included cognitive impairment (5/8), spastic dysuria (3/8), personality change and depression (3/8), ataxia (2/8), seizures (2/8), limb numbness (2/8), and developmental delay (2/8). When patients were diagnosed, the mean serum homocysteine level, the methyl malonic acid level in urine, the serum propionylcarnitine (C3) level and the ratios ofC3-to-acetylcarnitine (C2) and free carnitine (C0) were all dramatically elevated. Cranial MRIs showed nothing remarkable except mild brain atrophy. ...
Source: Journal of Neurology - Category: Neurology Source Type: research