Prenatal consequences of GALT deficiency in a rat model of classic galactosemia

The useful part

Prior reports document elevated galactose metabolites beginning in utero in CG, raising concern that long-term complications in CG might also trace their origins to the prenatal period. However, studies document that elevated galactose metabolites in the postnatal period do not predict later developmental complications, challenging the connection. Here, we explored the relationship between elevated galactose metabolites in utero and fetal outcome using a GALT-null rat model of CG.

How it works

• GALT-null fetal pups also showed significant growth delay in utero, but only when the dam and all siblings were GALT-null.
• To modify galactose metabolites in utero, we arranged rat crosses to produce GALT-null pups developing within either a GALT-null or heterozygous dam, and with or without heterozygous siblings.
• We reasoned that GALT activity present outside the fetus, but within the maternal-fetal compartment, might limit metabolic abnormalities in a developing GALT-null fetus -- and it did.
• When the dam was GALT-null, but some siblings were heterozygous, the median galactitol level in amniotic fluid was 2.45-fold higher.
• When the dam and all siblings were GALT-null, the median amniotic fluid galactitol level was 5.67-fold higher.

Details worth keeping

Dallas, Milan Cambon Ledesma, Yuhan Wu, Lauren E. That growth of GALT-null fetal pups was fully rescued by ges...