PART 1:
You are contacted by an attorney representing a client who has been
charged with child 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).
Golshani, K.R., Ludwig, M.R., Cohn, P.L., & Kruse, R. (2016). Osteogenesis Imperfecta.
Delaware Medical Journal, 88(6), 178-185.
http://proxy.chamberlain.edu:8080/login?
url=http://search.ebscohost.com/login.aspx?
direct=true&db=mdc&AN=27506061&site=eds-live&scope=site
McCance, K. L., Huether, S. E., Brashers, V. L., & Rote, N. S. (2013). Pathophysiology:
The biologic basis for disease in adults and children (7th ed.). St. Louis, MO:
Mosby.
PART:
Johnny is a 5-year-old Asian boy who is brought to a family practice
office with a “runny” nose that started about 1 week ago but has not
resolved. He has been blowing his nose quite frequently and “sores”
have developed around his nose. His mother states, “The sores started
as ‘big blisters’ that rupture; sometimes, a scab forms with a crust that
looks like “dried maple syrup” but continues to seep and drain.” She is
worried because the lesions are now also on his forearm. Johnny’s past
medical and family histories are normal. He has been febrile but is
otherwise asymptomatic. The physical examination was unremarkable
except for moderate, purulent rhinorrhea and 0.5- to 1-cm diameter
weeping lesions around the nose and mouth and on the radial surface of
the right forearm. There is no regional lymphadenopathy.
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