From: 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) | ||
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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 |