β‐Galactosidase therapy can mitigate blood galactose elevation after an oral lactose load in galactose mutarotase deficiency

Galactose mutarotase (GALM) deficiency (MIM# 618881), also known as type IV galactosemia, is caused by biallelic pathogenic variants of GALM. Cataracts are observed in patients with GALM deficiency as well as in other conditions associated with high levels of blood galactose and can be prevented by consuming a galactose-restricted diet or formula. Galactose restriction is the only known treatment for GALM deficiency and other types of galactosemia. We incidentally found that β-galactosidase might reduce blood galactose levels caused by lactose loading in GALM deficiency. Consequently, we investigated the effectiveness of β-galactosidase in decreasing the level of blood galactose in three patients with GALM deficiency. We performed two lactose loading tests per case: one with and one without β-galactosidase. The add-on administration of β-galactosidase significantly mitigated blood galactose elevations after lactose loading. Although urine galactitol was mildly elevated in all patients with GALM deficiency, β-galactosidase did not prevent increased levels of urine galactitol during the loading tests. No adverse events, including cataracts, were observed during or after the tests. Therefore, β-galactosidase could be a potential novel treatment agent for blood galactose elevation caused by lactose in patients with GALM deficiency. The effectiveness of β-galactosidase could possibly result in loosening of the galactose dietary restrictions or treatment for patients with GALM deficiency.