Table 2.

Disease course and treatment response in homocystinurias and methylation disorders

Disease	Disease course	Response to treatment
CBS deficiency B6-non responsive	Severe	Early, strict treatment results in favorable physical and cognitive outcome.
CBS deficiency B6-responsive	Mild to asymptomatic	Good response to pyridoxine
cblC defect	Severe	Early-onset: Survival, hematological and microangiopathy symptoms responsive. Neurological, opthalmological and developmental problems often ongoing Late-onset: Predominantly responsive, residual myelopathy/neuropathy frequent in prolonged untreated courses
cblD-Hcy defect cblD-MMA-Hcy defect	Severe	Variable, very limited data
cblF defect	Severe	Variable, very limited data
cblJ defect	Severe	Variable, very limited data
Severe MTHFR deficiency	Severe	Early betaine treatment is beneficial
cblE and cblG defect	Severe	Treatment seems beneficial in a majority of patients but response is variable. Individual case reports encourage early treatment
MAT I/III deficiency, heterozygous individuals	Predominantly benign	Generally good without treatment
MAT I/III deficiency, compound heterozygote and homozygote individuals	White matter disease, cognitive impairment observed	Methionine-lowering treatment may be beneficial but data is very limited
GNMT deficiency	Predominantly benign	Generally good without treatment
SAHH deficiency	Severe	Variable, very limited data
ADK deficiency	Severe	Unknown