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osteopetrosis (Albers-Schonberg disease)
Bones are overly dense & defective.
Epidemiology:
3 major types
1) malignant infantile form
a) disease is apparent from birth
b) incidence is 1 in 1000,000-500,000 births
2) intermediate form
a) less severe than the malignant infantile form
b) occurs in children < 10 years of age
3) adultform:
a) adults 20-40 years (mild form)
b) prevalence: 1 in 20,000
Pathology:
1) osteoclasts deficient in number or function, resulting in defective resorption of immature bone
2) all bones are affected
3) bones are overly dense
4) the skeleton is extremely heavy
5) bones, although dense, are also weak
6) overgrowth of bone may damage nerves & blood vessels, especially within the cranial vault
7) leukopenia & dysfunctional leukocytes
8) aplastic anemia (due to marrow failure)
Genetics:
1) malignant infantile form: autosomal recessive inheritance
- associated with defects in ATP6V0A3/TCIRG1 gene
- associated with defects in OSTM1 gene
- associated with defects in TNFSF11 (type 2)
- associated with defects in CLCN7 gene (type 4)
- associated with defects in TNFRSF11A gene (type 7)
2) intermediate form: autosomal recessive, autosomal dominant or sporadic
3) adult form: autosomal dominant
- type 1 associated with defects in LRP5
- type 2 associated with defects in CLCN7 (most common form)
4) large number of genetic abnormalities associated with osteopetrosis
Clinical manifestations:
1) malignant infantile form
- anemia
- frequent infections
- no tooth eruption or inadequate tooth eruption from the gums
- increased intracranial pressure
- macrocephaly
- failure to thrive
- delays in psychomotor development
- blindness, deafness, other brain disorders
- 30% 10 year survival
2) intermediate & adult forms
- fractures
- frequent infections
- blindness, deafness, strokes
3) autosomal dominant type 1 (OPTA1)
- generalized osteosclerosis most pronounced in the cranial vault
- patients are often asymptomatic, but some suffer from pain & hearing loss.
- appears to be the only type of osteopetrosis not associated with an increased fracture rate
4) autosomal dominant type 2
- sclerosis, predominantly involving the spine, the pelvis & the skull base
Laboratory:
- serum calcium low, value of 5.7 mg/dL (case report)
- alkaline phosphatase in serum & serum phosphate normal in same case report
- bone biopsy
- hypogammaglobulinemia (type 7)
Radiology:
1) dense bones are found on X-rays (image) [1]
2) brain MRI, CT (image) [1]
Complications:
- adult form
- fractures
- cranial nerve compression
- blindness, deafness, facial nerve paralysis
Management:
1) multidisciplinary team including
a) hematology
b) endocrinology
c) orthopedic surgery
2) pharmaceutical agent
a) Actimmune (interferon gamma-1b)
- only therapy specifically approved for osteopetrosis
- both adult & pediatric patients may benefit
b) bone marrow transplantation can be curative
c) high-dose calcitriol
d) prednisone may improve anemia
3) nutrition 4 physical therapy
5) occupational therapy
Prognosis:
1) infantile form: 30% 10 year survival
2) intermediate form: generally normal life expectancy
3) adult form: generally normal life expectancy
General
bone disease; osteopathia
developmental disorder
Database Correlations
OMIM correlations
References
- Yaga U, Panta P.
Images in Clinical Medicine: Osteopetrosis
N Engl J Med 2017; 376:e34. April 20, 2017
PMID: 28423297
http://www.nejm.org/doi/full/10.1056/NEJMicm1609871
- Information for Patients about Osteopetrosis
http://www.osteo.org/newfile.asp?doc=p117i&doctitle=Osteopetrosis&doctype=HTML+Fact+Sheet