Rethinking Newborn Screening: A Case of GALM Deficiency

Galactosemia is a group of hereditary disorders of galactose metabolism. A new type of galactosemia was discovered, caused by a deficiency in galactose mutarotase (GALM), which catalyzes the epimerization between beta- and alpha-D-galactose. All GALM-deficient patients reported in the literature (n = 44) had abnormal newborn screening (NBS) results or did not receive NBS (n = 2). We present the first patient with GALM deficiency who had negative NBS in the Netherlands and was identified at age 1.5 years during broad metabolic screening because of her global developmental delay, nystagmus, and a history of jaundice. Biochemical evaluation showed a significantly increased excretion of galactose (13,167 mmol/mol creatinine, upper limit of normal (ULN) 326) and galactitol (427 mmol/mol creatinine, ULN 71). Whole exome sequencing showed homozygous variants in <i>GALM</i> (c.424G>A p.(Gly142Arg)). A galactose-restricted diet was started, resulting in biochemical normalization. We present a comprehensive review of GALM-deficient patients, NBS data, and treatment. Different designs of galactosemia screening may lead to overlooking patients with GALM deficiency. Although the effects of lactose-restricted diet are largely unknown, a diet might prevent cataract in some patients.