Metabolic Diseases & Syndromes Flashcards
1
Q
Paget’s Disease
A
-
Mutation of SQSTM1 gene
- SQSTM1 gene provides instructions for making protein p62, which helps in regulating formation of osteoclasts
- Abnormal resorption & deposition of bone
- Bone broken down and replaced much faster than normal
- New bone is weaker and less organized than normal bone
- Distortion and weakening
- Unknown cause
- Inflammatory, genetic, and endocrine factors may play a role
- Characterized by abnormal & dysfunctional resorption & deposition of bone = weakening and deformation of bone
- Bowing of legs
- Enlargement of jaws
- Involves multiple areas of the skeleton
- Results in enlargement of skull, jaws, facial bones and deformity of spine & long bones
- Increased pathologic fracture
-
Occurs in pts >40yo
- Always >40yo
- More common w/ increasing age
- Gradual onset & chronic course
- Old white guys classically
- Narrowing of skull foramina leads to cranial nerve dysfunction
- Enlargement of jaws and widening of alveolar ridges
- Dentures don’t fit
- Spaces between teeth
- When jaws are involved, skull is also involved
- Enlarged cranium and bony deformity = stooped posture and bowing of legs
- Osteoporosis circumscripta: Large circumscribed areas of RL seen in early stages of disease
2
Q
Pagets Disease: Rad
A
- Early stages show decreased bone density
- Later stages, patchy, poorly-defined RO areas (“cotton wool”)
- During osteoblastic phase, patchy areas of sclerotic bone are formed which tend to become confluent
- Happens everywhere and not focal
- Different from fibrous dysplasia, which can be monostotic, always expansion, always under 20yo
- In all 4 quadrants and no expansion; always over 40yo
- Increased thickness of diploe of skill
- Multiple teeth w/ hypercementosis
- Lincoln’s Sign or Blackbeard: Uptake condyle to condyle
3
Q
Pagets Disease: Tx
A
- Chronic, slowly progressive, seldom causes of death of pt
- Can cause bone pain, bone deformity, neurologic problems
- Calcitonin and bisphosphonates inhibit osteoclastic resorption
- Not usually fatal, but has complications
- Increased incidence of osteosarcoma
4
Q
Pagets Disease: Lab values
A
- ↑serum alkaline phosphatase
- Normal blood Ca2+
- Normal blood phosphorus
- ↑urine hydroxyproline levels
5
Q
Hyperparathyroidism
A
-
Primary: Parathyroid gland hyperplasia, adenoma, carcinoma → increased PTH production
- Cause is from the gland itself and the main reason is because of an adenoma on one of the 4 parathyroid glands
-
Secondary: Kidney disease → Hypocalcemia → increased PTH production
- Not a problem w/ the gland itself
- Results from compensatory increase in the output of PTH in response to hypocalcemia either from kidney disease or decreased Vitamin D absorption due to diet
- Hypercalcemia leads to:
- Bone & joint pain
- Renal calculi
- Peptic ulcers
- Cognitive impairment
- Painful bones, renal stones, abdominal groans, psychotic moans
6
Q
Hyparathyroidism: Rad
A
- Generalized decrease in bone density → osteoporotic “ground glass” or “salt and pepper” appearance due to loss of trabeculation & lamina dura
- Loss of trabeculation, lamina dura, cortical plates
- Occasionally, giant cell tumors of bone (“brown tumors”)
- NO expansion, no displacement of teeth, not focal → can’t be fibrous dysplasia
7
Q
Hyperparathyroidism: Lab Features
A
- Primary: Increased serum Ca2+ (>12.5mg%) and PTH
- Secondary: Decreased or normal serum Ca2+; increased PTH
8
Q
Hyperparathyroidism: Microscopic
A
- Increased bone turnover
- Giant cell lesions identical to CGCG
- Osteoclastic resorption in hyperparathyroidism
- New bone formation in hyperparathyroidism
9
Q
Hyperparathyroidism: Tx
A
- Primary: Excision of parathyroid gland(s)
- Secondary: Renal dialysis or renal transplant
10
Q
Osteogenesis Imperfecta
A
- Group of genetic disorders w/ impaired collagen maturation
- COL1A1 OR COL1A2 mutations
- Defective cross-linking of collagen
- Osteoblasts produce defective osteoid
- Bones are brittle or fragile
- Congenital onset is more severe: Multiple fractures in utero; often die at birth or shortly after
- Later onset is milder: Normal lifespan
- Hallmark: Bone fragility
- Skeletal features:
- Multiple fractures: Sometimes bony deformity
- Radiographic: Thin cortical plates, multiple fractures, excessive callus formation
- Large skull w/ prominent facial bones
- Kyphosis and/or scoliosis
- Hyperextensible joints
- Thin cortical plates
- Eyes: Blue sclera
- Ears: Hearing loss
- Ligament laxity - bowing/deformity of long bones
- Increased prevalence of Class III malocclusion due to MX hypoplasia w/ or w/o MN hyperplasia
- Opalescent teeth: Diffuse blue-brown discoloration; slight translucence
11
Q
Osteogenesis Imperfecta: Tx
A
- No tx or cure
- Px varies from death at birth to normal lifespan
- # of bony fractures decreases w/ age
12
Q
Osoteopetrosis
A
- Osteoclasts are unable to resorb bone
- Marked thickening of bone density bc osteoclasts don’t stop laying down bone
- Defect in bone remodeling
- Increased density of bone (skull, jaws) and osteomyelitis
- Generalized hyperdensity of MX and MN w/ multiple malformed and impacted teeth
13
Q
Ectodermal Hyperplasia
A
-
2 Major types
- Anhidrotic: Partial or complete absence of eccrine sweat glands, sebaceous glands, hair follicles
- Hidrotic
- Facial abnormalities
- Prominent frontal bone
- Midface hypoplasia and saddle nose
- Skin & appendages
- Fine, sparse hair
- Scanty eyelashes & eyebrows
- Decreased eccrine sweat glands → decreased sweating → heat intolerance and fever
- Dry skin
- Hypoplastic or aplastic nails
- Oral manifestations
- Hypodontia or anodontia of primary and permanent dentitions
- Hypoplasia of alveolar ridges
- Decreased vertical dimension
- Protuberant lips
- Cone-shaped teeth
- Unerupted teeth
- Xerostomia
14
Q
Ectodermal Dysplasia: Tx
A
- Cool envt
- Lube for dry skin
- Dental prostheses
- Bone grafting & implants
- Dentures
- Normal lifespan
15
Q
Cherubism
A
- Mutation of SH3BP2 gene
- Controls osteoclasts & osteoblasts
- Autosomal dominant, genetic disease
- Clinical features usually appear by 10yo
- Progressive, non-tender swelling of jaws
- MN almost always involved
- Swelling → Round “cherubic” face
- Stops growing at some point
- Eyes tilted up
- Progressive, nontender swelling of jaws
- MN almost always involved
- Radiographic features
- Bilateral RL features → expansion & sometimes perforation of cortices
- Multilocular RL areas
- Multiple unerupted teeth are displaced by lesions
- Premature exfoliation of primary teeth and unerupted permanent teeth
- Not true hypodontia bc teeth haven’t fully developed
- Bilateral, multilocular, expansile RL lesions
- Giant cells like hyperparathyroidism and CGCG
