Muscular dystrophy + Osteogenesis imperfecta Flashcards
Duchenne Muscluar dystrophy Ex and PPx:
- X-linked recessive disorder
- Mutation causing dystrophy of dystrophin (connects cytoskeleton of muscle fibre to surround extracellular matrix)
- Dystrophin deficiency - MYOFIBRIL NECROSIS with replacement by fibroadipose tissue.
- Typically in boys 1-6 yrs
- Life expectancy - late twenties - due to respiratory failure/cardiomyopathy
Presentation of DMD?
1) Waddling, clumsy gait
2) Classic Gower’s sign - using hands to climb up leg
3) Distal girdle muscles affected late
4) Selective wasting causes calf pseudo hypertrophy - (fibroadipose tissue makes muscles look large)
5) Progressive atrophy and weakness - wheelchair needed at 9-12
6) Respiratory involvement and infections
7) Cardiomyopathy and orthopaedic problems e.g. tendon contractors, scoliosis and osteoporosis
8) Learning difficulties in 1/3rd
Diagnosing DMD?
1) Raised CK (creatinine kinase) - measure in all boys not walking by 1.5 years
2) Muscle biopsy - abnormal fibres surrounded by fat and fibrous tissue
3) Genetic testing
Treating DMD?
1) Physiotherapy - maintain power and mobility and delay scoliosis
2) Prednisolone - slows decline in strength and function
3) Orthoses - help prolong walking
4) Overnight CPAP to prevent nocturnal hypoxia
Difference between Becker’s and Duchenne’s?
- Average onset of Becker’s is later (11 yrs).
- Mutation results in some functional dystrophin production - less severe than Duchenne’s
Presentation of Becker’s MD?
1) Similar to Duchenne’s but rate of progression slower.
2) Inability to walk in late 20s + wheelchair needed - later the in Duchenne’s
3) Life expectancy of late 40s - normal.
Diagnosis of Becker’s MD?
1) Raised CK
2) Muscle biopsy
3) Genetic testing
Treatment of Becker’s MD?
1) Physio and exercise to maintain muscular power and mobility.
2) Prednisolone - preserve strength and function.
What is Osteogenesis Imperfecta (Brittle bone syndrome) ?
Group of disorders of collagen metabolism causing bone fragility with bowing and frequent fractures.
NORMAL life expectancy
Classification of Osteogenesis Imperfecta?
I - mildest + most common (autosomal dominant)
II - lethal (autosomal dominant)
III - severe form - autosomal recessive
IV - moderate
Clinical presentation of Osteogenesis imperfecta?
1) Joint laxity and fragile, low-density bones with recurrent fracture
2) CHILDHOOD OSTEOPOROSIS (low bone mass, increase in fragility)
Most common (type I) - Childhood fractures, blue appearance to sclerae, some develop hearing loss. Type II - multiple fractures before birth, associated with stillbirth
Diagnosis of Osteogenesis imperfeca?
1) X-ray - many fractures, osteoporotic bones with thin cortex and bowing deformity of long bones
2) Immature unorganised bone with abnormal cortex
Treatment of Osteogenesis imperfecta?
1) Prevent injury
2) Physio, rehab and occupational therapy
3) Bisphosphonates to reduce fracture rate - Alendronic acid
4) Treat fractures - with splinting to prevent limb deformity
Vitamin D deficiency PPx:
- Deficient intake or defective metabolism of vitamin D resulting in low serum Ca2+.
- Low Ca2+ triggers release of PTH resulting in demineralisation of bone - resulting in Ca2+ release (normalisation of Ca2+)
- PTH also results in renal losses of phosphate and consequently low serum phosphate - reducing potential for bone calcification
Vitamin D deficiency presentation:
1) Bone deformity and classic picture of rickets
2) Can present without bone abnormalities, but with symptoms of hypocalcaemia (seizures, apnoea, stridor, NM irritability/tetany)
3) Presentation more common before 2 years of age and in adolescence - high demand for Ca2+ in rapidly growing bone - hypocalcaemia before rickets develops
