TGDS (TDP-glucose 4,6-dehydratase) is a nucleotide sugar metabolic enzyme that catalyzes the conversion of UDP-glucose into UDP-4-keto-6-deoxyglucose 1. This enzyme plays a critical role in glycosaminoglycan biosynthesis and skeletal development 1. Beyond its canonical metabolic function, TGDS produces an 'enzyme-rescue metabolite' that maintains the activity of the enzyme UXS1 under conditions of low NAD+ availability 1. The UDP-4-keto-6-deoxyglucose product mimics UXS1's reaction intermediate and regenerates essential NAD+ cofactor within the catalytic pocket, completing the UXS1 catalytic cycle when cellular NAD+ is scarce 1. Loss-of-function mutations in TGDS cause Catel-Manzke syndrome, an autosomal recessive skeletal dysplasia characterized by Pierre Robin sequence and bilateral digital malformations 23. The pathogenic variants impair enzyme activity and protein stability 4. Disease manifestations result from impaired glycan synthesis essential for skeletal development due to UXS1 inactivation 1. The phenotypic spectrum of TGDS-associated Catel-Manzke syndrome extends beyond the cardinal features to include disproportionate short stature 3. Zebrafish models confirm tgds's role in craniofacial cartilage development and sulfate glycosaminoglycan synthesis 4.