Аннотация
Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare
inborn disorder of L-lysine, L-hydroxylysine, and
L-tryptophan metabolism complicated by striatal damage
during acute encephalopathic crises. Three decades after
its description, the natural history and how to treat this
disorder are still incompletely understood. To study which
variables influenced the outcome, we conducted an
international cross-sectional study in 35 metabolic
centers. Our main outcome measures were onset and
neurologic sequelae of acute encephalopathic crises. A
total of 279 patients (160 male, 119 female) were included
who were diagnosed clinically after clinical presentation
(n = 218) or presymptomatically by neonatal screening (n =
23), high-risk screening (n = 24), or macrocephaly (n =
14). Most symptomatic patients (n = 185) had
encephalopathic crises, characteristically resulting in
bilateral striatal damage and dystonia, secondary
complications, and reduced life expectancy. First crises
usually occurred during infancy (95\% by age 2 y); the
oldest age at which a repeat crisis was reported was 70 mo.
In a few patients, neurologic disease developed without a
reported crisis. Differences in the diagnostic criteria and
therapeutic protocols for patients with GCDH deficiency
resulted in a huge variability in the outcome worldwide.
Recursive partitioning demonstrated that timely diagnosis
in neurologically asymptomatic patients followed by
treatment with L-carnitine and a lysine-restricted diet was
the best predictor of good outcome, whereas treatment
efficacy was low in patients diagnosed after the onset of
neurologic disease. Notably, the biochemical phenotype did
not predict the clinical phenotype. Our study proves GCDH
deficiency to be a treatable disorder and a good candidate
for neonatal screening.
Пользователи данного ресурса
Пожалуйста,
войдите в систему, чтобы принять участие в дискуссии (добавить собственные рецензию, или комментарий)