Enzyme replacement prevents neonatal death, liver damage, and osteoporosis in murine homocystinuria

<div>Classical homocystinuria (HCU) is an inborn error of sulfur amino acidmetabolism caused by deficient</div><div>activity of cystathionine b-synthase (CBS), resulting in an accumulation of homocysteine and a concomitant decrease</div><div>of cystathionine and cysteine in blood and tissues. Inmice, the complete lack of CBS is neonatally lethal. In</div><div>this study, newborn CBS-knockout (KO) mice were treated with recombinant polyethyleneglycolylated human</div><div>truncatedCBS (PEG-CBS). Full survival of the treatedKOmice, along with a positive impact onmetabolite levels in</div><div>plasma, liver, brain, and kidneys, was observed. The PEG-CBS treatment prevented an otherwise fatal liver disease</div><div>characterized by steatosis, death of hepatocytes, and ultrastructural abnormalities of endoplasmic reticulum</div><div>andmitochondria. Furthermore, treatment of the KOmice for 5mo maintained the plasma metabolite balance and</div><div>completely prevented osteoporosis and changes in body composition that characterize both the KO model and</div><div>humanpatients. These findings argue that early treatment of patients withHCUwith PEG-CBSmay prevent clinical</div><div>symptoms of the disease possibly without the need of dietary protein restriction.</div>