Outcome of the first 3-years of a DNA-based neonatal screening program for glutaric acidemia type 1 in Manitoba and northwestern Ontario, Canada.

摘要: Glutaric acidemia type 1 (GA1) is overrepresented in the aboriginal population of Island Lake, Manitoba, and northwestern Ontario who speak Ojibway-Cree (Oji-Cree) dialect. The carrier frequency these communities has been predicted to be as high 10 individuals. Prior beginning newborn screening for GA1 May 1998, 18 20 affected patients diagnosed at this center have from high-risk communities. Most followed an acute encephalopathic course with permanent neurologic sequelae mortality. They excrete small amounts glutaric acid 3-hydroxyglutaric significant residual enzyme activity. A single homozygous mutation glutaryl-CoA-dehydrogenase (GCDH IVS-1 + 5g right arrow t) identified population. DNA-based targeted our was begun order provide presymptomatic detection treatment patients. Of first 1176 newborns screened, 4 infants were treated a low-protein diet, carnitine, riboflavin. All required numerous hospitalizations intercurrent illnesses. Eventually, 3 presented dystonic encephalopathy seizures along neurological sequelae. One died unexpectedly home months age. fourth, now 9 old, had gastrostomy tube placed facilitate fluid replacement addition standard protocol doing well. reasons initial disappointing outcomes babies are likely multiple. Based on early experience that other centers GA1, current therapeutic strategies may insufficient preventing occurrence some children. An incomplete understanding neurotoxic mechanisms underlying devastating disorder hampers effective management.