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.