NR 507 Week 6 TD and Quiz
NR 507 Week 6 TD and Quiz
PART 1:
You are contacted by an attorney representing a client who has been
charged with child
... [Show More] abuse and whom faces loss of her child and 15 years
in prison. The record indicated that the child was 4 years old and
presented to the ER room with a broken arm and a broken leg. There
also appeared to be multiple previous fractures. Now, you examine the
child and find blue sclera, a sunken chest wall, severe scoliosis, and you
observe a triangular face and prominent forehead. You confirm that
there have been multiple previous fractures by evaluating the previous
X-rays. This is a genetic disorder.
What is the most likely genetic disease that this presents and why?
What is the molecular basis of this disease?
Before, calling the police what should the initial clinician have
done?
The presenting genetic disease is most likely osteogenesis imperfecta (OI), also
known as brittle bone disease. OI consists of a diverse group of symptoms related to
genetic mutations found in type 1 collagen biosynthesis (Golshani, Ludwig, Cohn, &
Kruse, 2016). The Sillence classification system delineates OI based on the severity of
the disease. Types II and III are the most severe, are characterized by autosomal recessive
inheritance, can cause severe deformity in the neonate, stillbirth, and these patients have a
short life expectancy (McCance, Huether, Brashers, & Rote, 2013). Types I and IV are
considered less severe forms, are characterized by inherited autosomal dominant trait,
and the onset varies in age from childhood to adulthood (McCance et al., 2013). The
main characteristics of OI include low bone mass and elevated bone fragility that leads to
fractures and deformities (Golshani et al., 2016). The classic manifestations associated
with OI are osteoporosis like and include an increased incidence of fractures, triangular
facies, possible bony deformations, poor dentition, possible blue sclera, and possible
vascular weaknesses (McCance et al., 2013).
To fully understand the disease process, it is important to know what happens at
the molecular level in regards to the biosynthesis of type 1 collagen. First, procollagen is
created via rough endoplasmic reticulum as triple helix that form two collagen chains,
a1(I) and a2(I), which are encoded by the COLIA1 and COILA2 genes (Golshani et al.,
2016). Both chains have C and N terminal peptides (Golshani et al., 2016). These chains
also have domains with repetitive amino acid sequence that contain glycine by every
third amino acid, which permits the triple helix arrangement (Golshani et al., 2016). Once
post-translational modifications and folding occurs, the procollagen molecule is carried to
the extracellular matrix, cleavage of the terminal propeptides takes place, and the
collagen molecule forms (Golshani et al., 2016). When the collagen molecule forms, it
forms fibrils via covalent bonding inside and in the middle of triple helix molecules
(Golshani et al., 2016). Additionally, the fibrils formed will accumulate and produce type
1 collagen fibers (Golshani et al., 2016).
Upon examination, medical professionals may find evidence of bone fractures in
various stages of healing, including fractures of the skull, metaphysis bones, and ribs,
leading to the suspicion of child abuse (Golshani et al., 2016). While OI is rare, it should
still be included in ones differential diagnosis (Golshani et al., 2016). Evaluation and
treatment of OI is established by the presence of clinical manifestations, therefore it is
very important clinicians are able to recognize them (McCance et al., 2013). In all types
of the disease process, serum alkaline phosphate levels will be elevated (McCance et al.,
2013). Another way to evaluate OI is by culturing skin fibroblast collagen via
electrophoresis; 95 percent of people tested who have OI show a decreased amount of
collagen (McCance et al., 2013). The initial clinician should have questioned the child’s
symptoms; diagnosis of OI is distinct when some key elements exist including blue
sclera, scoliosis, wormian bones, and a family history (Golshani et al., 2016). Without
these features, diagnosis can be difficult (Golshani et al., 2016). [Show Less]