|
Summary of the key clinical manifestations, onset, severity, treatment, prognosis and recurrence risks of the main types of osteopetrosis |
|||||||||
| Osteopetrosis subtype |
Autosomal recessive osteopetrosis (ARO) |
X-linked osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia and immunodeficiency (OLEDAID) |
Intermediate osteopetrosis (IRO) |
Autosomal dominant osteopetrosis (Albers-Schönberg disease) |
|||||
|
|
|||||||||
| Classic |
Neuropathic |
ARO with RTA |
|||||||
|
|
|||||||||
| Genetic basis |
TCIRG |
CLCN7, OSTM1 |
Carbonic anhydrase II |
IKBKG (NEMO) |
CLCN7, PLEKHM1 |
CLCN7 |
|||
|
|
|||||||||
| Skeletal manifestations |
Increased bone density, diffuse and focal sclerosis of varying severity Modelling defects at metaphyses Pathological fractures Osteomyelitis Dental abnormalities: tooth eruption defects and dental caries |
||||||||
|
|
|||||||||
| Other manifestations |
Pancytopaenia. Extramedullary haematopoiesis, hepatosplenomegaly. Cranial nerve compression (II, VII, VIII) Hydrocephalus Hypocalcaemia |
As for classic ARO, but primary neurodegeneration, including retinal atrophy |
Renal tubular acidosis. Developmental delay. Intracranial calcification. Cranial nerve compression. Bone marrow impairment rare. |
Anhidrotic ectodermal dysplasia. Lymphedema. Immunodeficiency resulting in overwhelming infection. |
Anaemia and extramedullary haematopoiesis Occasional optic nerve compression |
Moderate haematological failure Cranial nerve compression |
|||
|
|
|||||||||
| Onset |
Perinatal |
Perinatal |
Infancy |
Infancy |
Childhood |
Late childhood or adolescence |
|||
|
|
|||||||||
| Severity |
Severe |
Severe |
Moderate |
Severe |
Mild to moderate |
Mild to moderate, occasionally severe |
|||
|
|
|||||||||
| Treatment |
Supportive HSCT |
Supportive |
Supportive May benefit from HSCT |
Supportive |
Supportive |
Supportive |
|||
|
|
|||||||||
| Prognosis |
Poor Fatal in infancy |
Poor Fatal in infancy |
Variable |
Poor Fatal in early childhood |
Variable |
Normal life expectancy |
|||
|
|
|||||||||
| Recurrence risk |
Parents of proband: 25% risk of recurrence in future pregnancies |
If mother of proband carrier: 50% of male pregnancies affected |
Parents of proband: 25% risk of recurrence in future pregnancies |
50% in future pregnancies if one parent affected |
|||||
Stark and Savarirayan Orphanet Journal of Rare Diseases 2009 4:5 doi:10.1186/1750-1172-4-5 |
|||||||||