Diagnosis and clinical management of enzymopathies

Abstract

At least 16 genet i cally deter mined con di tions qual ify as red blood cell enzymopathies. They range in fre quency from ultrarare to rare, with the excep tion of glu cose - 6 - phos phate dehy dro ge nase defi ciency, which is very com mon. Nearly all these enzymopathies man i fest as chronic hemo lytic ane mias, with an onset often in the neo na tal period. The diag no sis can be quite easy, such as when a child pres ents with dark urine after eat ing fava beans, or it can be quite dif fi cult, such as when an adult pres ents with mild ane mia and gall stones. In gen eral, 4 steps are recommended: (1) rec og niz ing chronic hemo lytic ane mia; (2) exclud ing acquired causes; (3) exclud ing hemo glo bin op a thies and membranopathies; (4) pinpointing which red blood cell enzyme is defi cient. Step 4 requires 1 or many enzyme assays; alter na tively, DNA test ing against an appro pri ate gene panel can com bine steps 3 and 4. Most patients with a red blood cell enzymopathy can be man aged by good sup port ive care, includ ing blood trans fu sion, iron che la tion when nec es sary, and sple nec tomy in selected cases; how ever, some patients have seri ous extraerythrocytic man i fes ta tions that are dif fi cult to man age. In the absence of these, red blood cell enzymopathies are in prin ci ple ame na ble to hema to poi etic stem cell trans plan ta tion and gene ther apy / gene editing.