Table 2 Summary of the key clinical manifestations, onset, severity, treatment, prognosis and recurrence risks of the main types of osteopetrosis
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) | ||
|---|---|---|---|---|---|---|
| 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 | ||