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Severe cases of homocystinuria are typically caused by autosomal recessive genetic defects and exhibit characteristic clinical features including ocular lens dislocation, marfanoid features and other skeletal abnormalities including osteoporosis, intellectual disability, and thromboembolic disease, the latter frequently being the cause of premature death in affected individuals ( Cystathionine β-synthase deficiency Homocysteine, in its oxidized disulfide form (Figure 1), was first detected in the urine of two siblings with intellectual disability in Ireland in 1963 ( Inherited disorders of vitamin B12 absorption, transport, and metabolism The years following the discovery of homocysteine brought considerable developments in our understanding of the metabolic role of vitamin B12 (also known as cobalamin)