Saccharopinuria

Saccharopinuria, also known as saccharopinemia or hyperlysinemia type II, is an extremely rare inborn error of lysine metabolism caused by a deficiency of the enzyme saccharopine dehydrogenase (also called aminoadipic semialdehyde synthase), which catalyzes the second step in the lysine degradation pathway. This results in the accumulation of saccharopine and lysine in blood and urine. The condition is classified under disorders of lysine and hydroxylysine metabolism (ICD-10: E72.3). The clinical significance of saccharopinuria remains debated. Some affected individuals have presented with intellectual disability, short stature, and spastic diplegia, while others identified through newborn screening or family studies have been entirely asymptomatic. Neurological features, when present, may include developmental delay and varying degrees of cognitive impairment. Because many individuals with elevated saccharopine levels are clinically normal, some experts consider saccharopinuria to be a benign biochemical variant rather than a true disease. The condition primarily affects the nervous system when symptomatic. There is no specific treatment for saccharopinuria. Dietary restriction of lysine has been attempted in some cases, but its clinical benefit remains unproven given the uncertain pathogenicity of the biochemical finding. Management, when warranted, is supportive and may include developmental therapies for individuals with intellectual disability or motor difficulties. Genetic counseling is recommended for affected families.

Common questions about Saccharopinuria