Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by severe fetal growth restriction, microcephaly, a distinct facial appearance, ichthyosis, skeletal anomalies, and perinatal lethality. Through a positional-mapping study combining autozygosity mapping and whole-exome sequencing, Shaheen and colleagues surprisingly found that NLS is caused by mutations in PHGDH encoding for 3-phosphoglycerate dehydrogenase is the first enzyme in the phosphorylated pathway of de novo serine synthesis. PHGDH mutations were previously known to be responsible for microcephaly and developmental delay. Complete deficiency of PHGDH mouse ortholog recapitulates the key features of NLS. In conclusion, NLS is the extreme end of an inborn error of serine metabolism.
Posted by Nicola Brunetti-Pierri, MD, FACMG