[2] Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment.
Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.
Amino acid changes in the catalytic domains or those in contact with substrate or cofactors were the main cause of these variations of D-BP deficiency.
[4] D-BP is expressed throughout the entire human body, with the highest mRNA levels in the liver and brain.
Type I patients showed only deletions, insertions, and nonsense mutations were identified, most leading to shortened polypeptides.
Most type II patients show missense mutations in D-BP hydratase unit as well as some in-frame deletions.
Type III"individuals commonly show missense mutations in the coding region of the dehydrogenase domain.
Other amino acid side chains alter the shape of this loop due to steric hindrance, and prevent proper NAD+ binding.
[4] The most common clinical observations of patients with D-bifunctional protein deficiency include hypotonia, facial and skull dysmorphism, neonatal seizures, and neuronal demyelination.