Albers-Schnberg disease


Albers-Schnberg disease (Autosomal dominant osteopetrosis type II)

Description, Causes and Risk Factors:

Albers-Schnberg disease is a rare hereditary condition. It has been known by various names since its first clinical description in the medical literature in 1904. It is essentially a disease of childhood manifesting itself during the first year of life but in some ceases the symptoms may not be apparent until adolescence or adult life. The exact type of inheritance in autosomal dominant osteopetrosis type II disease is uncertain. Males and females are equally affected. It may be sporadic and in only about half the cases can a familial history be demonstrated.

Albers-Schnberg disease

This disease is congenital in origin and starts in utero. The affected children may be born with hydrocephalus and often show symptoms suggestive of compression' of the cranial nerves especially of the optic and the acoustic. They are markedly anemic and seldom survive inspire of repeated transfusions of blood.

The etiology remains obscure. There is no evidence that endocrine disturbances, dietary deficiency, toxaemia or faulty calcium and phosphorus metabolism have an etiological role. It is a true developmental disease which is manifested by the persistence of a primitive type of bone and seems to be due to an abnormal property of the parental germplasm.

By linkage analysis, the presence, on chromosome 1p21, of a gene causing Albers-Schnberg disease was previously suggested. However, analysis of further families with autosomal dominant osteopetrosis type II indicated genetic heterogeneity within Albers-Schnberg disease, with the chromosome 1p21 locus being only a minor locus. Researchers now performed a genome-wide linkage scan of a French extended family with autosomal dominant osteopetrosis type II, which allows them to localize an Albers-Schnberg disease gene on chromosome 16p13.3.

Analysis of microsatellite markers in five further families with autosomal dominant osteopetrosis type II could not exclude this chromosomal region. A summed maximum LOD (logarithm of odds) score of 12.70 was generated with marker D16S3027, at a recombination fraction theta of 0. On the basis of the key recombinants in the families, a candidate region of 8.4 cM could be delineated, flanked by marker D16S521, on distal side, and marker D16S423, on the proximal side. Surprisingly, one of the families analyzed is the Danish family previously suggested to have linkage to chromosome 1p21. Linkage to chromosome 16p13.3 clearly cannot be excluded in this family, since a maximum LOD score of 4.21 at theta=0 is generated with marker D16S3027. Because at present no other family with Albers-Schnberg disease has proved to have linkage to chromosome 1p21, we consider the most likely localization of the disease-causing gene in this family to be to chromosome 16p13.3. This thus reopens the possibility that autosomal dominant osteopetrosis type II is genetically homogeneous because of a single gene on chromosome 16p13.3.

A contrast must also be made between autosomal dominant osteopetrosis (ADO) and autosomal recessive osteopetrosis (ARO). Although the latter may occur secondary to homozygous or compound heterozygous mutations in the ClCN7 gene, the majority of ARO cases result from mutations in TCIRG1 encoding the a3 subunit of the vacuolar proton pump.

The adult form of autosomal dominant osteopetrosis type II affects approximately 1,250 people in the US. The most severe form, malignant infantile osteopetrosis, is very rare, affecting only 8 to 40 children born in the US each year. It is difficult to estimate how often the different forms of osteopetrosis occur worldwide.

The severe infantile forms are associated with diminished life expectancy, with most untreated children dying in the first decade as a complication of bone marrow suppression. Life expectancy in the adult onset forms is normal.

Symptoms:

Albers-Schnberg disease is characterized by widespread osteosclerosis and the radiographic finding of endobones (“bone within a bone” appearance) best manifested by the classic “rugger-jersey” identified in the vertebral bodies of affected individuals.

Cranial nerve involvement responsible for hearing loss, bilateral optic atrophy, and/or facial palsy was also found in patients. This large series sheds new light on several aspects of ADO II, most notably the possibility of severe clinical complications.

Individuals with autosomal dominant osteopetrosis type II may also have markedly elevated serum levels of tartrate-resistant acid phosphatase and the BB isoenzyme of creatine kinase. Tartrate-resistant acid phosphatase levels may also correlate to and be useful for predicting the clinical severity of disease.

Diagnosis:

The mainstay of diagnosis is clinical and largely depends on the radiographic appearance of the skeleton. X-rays of Albers-Schnberg disease patients may have an unusual density with a chalky white appearance. Bone density tests and bone biopsies can confirm the diagnosis while other tests such at CAT scans or MRI can be performed to evaluate any potential complications.

Genetic testing is available either clinically or on a research basis for many of the genes implicated in osteopetrotic conditions. Genetic testing can be used to confirm the diagnosis and differentiate between different subtypes of osteopetrosis, providing additional information regarding prognosis, likely response to treatment and recurrence risks.

Treatment:

Treatment is largely symptomatic and often involves meticulous fracture management and close postoperative care. At present, no effective medical treatment for autosomal dominant osteopetrosis type II. Treatment is largely supportive and is aimed at providing multidisciplinary surveillance and symptomatic management of complications.

    Fractures and arthritis are common and require treatment by an experienced orthopedic surgeon due to the brittleness of the bone, and the relatively frequent occurrence of secondary complications such as delayed union or non-union of fractures and osteomyelitis.

  • Hypocalcemic seizures are treated with calcium and vitamin D supplementation, and bone marrow failure with red blood cell and platelet transfusions.

  • Regular ophthalmologic surveillance including visual evoked potentials (VEPs) is important in detecting optic nerve atrophy.

  • Surgical decompression of the optic nerve has been performed to prevent vision loss.

  • Dental problems such as delayed tooth eruption, ankylosis, abscesses, cysts and fistulas are common. Therefore, routine dental surveillance and maintenance of oral hygiene form an integral part of management and play an important role in preventing more severe complications such as osteomyelitis of the mandible.

  • Bone marrow transplant may also be useful in treatment. Bone marrow transplant has many risks, but if it is successful it saves the life of a child who would otherwise die from complications of the disorder.

NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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