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Autosomal Recessive Osteopetrosis Type 1

Last updated May 1, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Autosomal Recessive Osteopetrosis Type 1, or Infantile Malignant Osteopetrosis, is a rare congenital disorder of bone resorption characterized by generalized skeletal densification.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Autosomal Recessive Malignant Osteopetrosis 
  • Autosomal Recessive Marble Bones
  • Infantile Malignant Osteopetrosis Type 1

What is Autosomal Recessive Osteopetrosis Type 1? (Definition/Background Information)

  • Osteopetrosis refers to a group of rare, inherited skeletal disorders characterized by increased bone density and abnormal bone growth

(Source: Osteopetrosis, Autosomal Recessive, 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

  • Autosomal Recessive Osteopetrosis Type 1, or Infantile Malignant Osteopetrosis, is a rare congenital disorder of bone resorption characterized by generalized skeletal densification
  • The disease is heterogeneous. Over 50% of cases are due to mutations in the TCIRG1 gene and another 10% are due to mutations in the CLCN7 gene. A small number of patients have been described with mutations in the OSTM1 gene. Transmission is autosomal recessive
  • Bone marrow failure, fractures and visual impairment are the classical features of the disease, which begins in early infancy or in fetal life. It results from the failure of osteoclasts to resorb immature bone
  • Patients may require blood transfusions, treatment for infections and management of their developmental and visual problems. Bone marrow transplant can alleviate many features of the disease, but needs to be performed early to minimize optic nerve encroachment
  • The prognosis of Autosomal Recessive Osteopetrosis Type 1 is variable, but improves if bone marrow transplant is performed early

(Source: Autosomal Recessive Malignant Osteopetrosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Autosomal Recessive Osteopetrosis Type 1? (Age and Sex Distribution)

  • Autosomal Recessive Osteopetrosis Type 1 is a rare congenital disorder. The presentation of symptoms may occur at birth
  • The estimated frequency of occurrence of this disorder is about 1 in 200,000 live births
  • Both males and females may be affected
  • Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Autosomal Recessive Osteopetrosis Type 1? (Predisposing Factors)

  • A positive family history may be an important risk factor, since Autosomal Recessive Osteopetrosis Type 1 can be inherited
  • A child born to consanguineous parents bears an increased risk of developing this bone disorder 

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Autosomal Recessive Osteopetrosis Type 1? (Etiology)

Autosomal Recessive Osteopetrosis Type 1 may be caused by mutations in at least 3 different genes.

  • Mutations in the TCIRG1 gene cause more than half of all the cases
  • Additionally, mutations in CLCN7 (constitutes 10% of all cases) and OSTM1 genes may also cause the disorder
  • Autosomal Recessive Osteopetrosis Type 1 is inherited in an autosomal recessive manner

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Autosomal Recessive Osteopetrosis Type 1?

The signs and symptoms of Autosomal Recessive Osteopetrosis Type 1 may include:

  • Anemia
  • Carious teeth
  • Coxa vara
  • Elevated alkaline phosphatase
  • Facial palsy
  • Facial paralysis
  • Flared metaphysis
  • Frontal bossing
  • Hearing impairment
  • Hepatomegaly
  • Macrocephaly
  • Ophthalmoparesis
  • Osteomyelitis
  • Osteopetrosis
  • Pancytopenia
  • Pathologic fracture
  • Sandwich appearance of vertebral bodies
  • Splenomegaly
  • Tetany

(Source: Autosomal Recessive Osteopetrosis 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Autosomal Recessive Osteopetrosis Type 1 Diagnosed?

Autosomal Recessive Osteopetrosis Type 1 is diagnosed on the basis of the following information:

  • Complete physical examination
  • Thorough medical history evaluation
  • Assessment of signs and symptoms
  • Laboratory tests
  • Imaging studies
  • Biopsy studies, if necessary
  • Molecular genetic testing of fetal cells early in pregnancy (11-13 weeks of gestation)
  • Prenatal ultrasound to check for fetal abnormalities (typically in the last trimester)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Autosomal Recessive Osteopetrosis Type 1?

The potential complications of Autosomal Recessive Osteopetrosis Type 1 may include:

  • Severe anemia, which may lead to extreme fatigue and fainting spells
  • Vision impairment; permanent loss of vision
  • Problems with movement due to brittle bones susceptible to fractures
  • Compromised central nervous system
  • Failure to thrive

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Autosomal Recessive Osteopetrosis Type 1 Treated?

The treatment for Autosomal Recessive Osteopetrosis Type 1 may include the following:

  • Blood transfusions
  • Treatment for infections 
  • Management of developmental and visual problems
  • Bone marrow transplant can alleviate many features of the disease but needs to be performed early to minimize optic nerve encroachment

(Source: Autosomal Recessive Malignant Osteopetrosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Autosomal Recessive Osteopetrosis Type 1 be Prevented?

Autosomal Recessive Osteopetrosis Type 1 may not be preventable, since it is a genetic disorder.

  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
  • Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Autosomal Recessive Osteopetrosis Type 1? (Outcomes/Resolutions)

  • The prognosis of Autosomal Recessive Osteopetrosis Type 1 is dependent upon the severity of the signs and symptoms and associated complications, if any
  • Individuals with mild conditions have better prognosis than those with severe symptoms and complications
  • Early diagnosis and adequate treatment of the condition along-with a bone marrow transplant is known to help improve outcomes

(Source: Autosomal Recessive Malignant Osteopetrosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Autosomal Recessive Osteopetrosis Type 1:

Autosomal Recessive Osteopetrosis Type 1 is also known by the following additional names:

  • Autosomal Recessive Osteopetrosis 1
  • Infantile Malignant Osteopetrosis
  • OPTB1

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 1, 2018
Last updated: May 1, 2018