Conclusions
In this paper, we give clinical and structural evidence of pathogenicity of the novel, inframe variant - c.472_477del. We emphasize the need for rapid genetic diagnosis, next-generation sequencing (NGS), in metabolic diseases, especially in cases with unclear clinical picture or when the prognosis is poor. The described mutation modifies the binding cavity of the catalytic subunit, and the preliminary structural analysis shows two potential processes that can be distorted. We can speculate, that if the heterodimer formation is preserved, the deficiency caused by abnormal precursor Z binding could be perhaps limited, but a chemical modification of the precursor, whereas the changes in carrier subunit binding would be much more challenging to reverse.