Marble Disease

What is Marble Disease?

Marble disease is also known as osteoporosis, Albers-Schoenberg disease. Occurs in persons of both sexes.

Marble disease is a disease in which an increased amount of compact substance is produced in most bones of the skeleton, combined with the development of dense bone tissue in the bone marrow canals. The disease was first described by the German surgeon Albers-Schönberg (N.E. Albers-Schonberg) in 1904. It is rare. Compared with other diseases with hyperostosis, it is described in most detail (more than 300 cases).

Causes of Marble Disease

Currently, three genes have been found, mutations in which lead to the development of autosomal recessive marble disease in humans. All these genes encode proteins necessary for the normal functioning of osteoclasts that can destroy bone tissue. Most cases of this form of the disease are caused by mutations in the TCIRG1 gene (T-cell immune regulator 1 gene) encoding an osteoclast-specific a3 isoform of one of the subunits of the transmembrane vacuolar ATP-dependent proton pump. It is in this gene that the c.807 + 5g – (IVS8 + 5g -) mutation is the cause of all all cases of marble disease.

Pathogenesis during Marble Disease

The increase in the amount of compact bone substance is associated with the ability of the mesenchyme to retain more than normal amount of salts. In zones of endosteal and enchondral ossification, an excess amount of sclerosed tissue develops.

Symptoms of Marble Disease

There are two forms of marble disease: manifested at an early age with pronounced symptoms and occurring without visible clinical manifestations and diagnosed only during X-ray examination.

The disease is characterized by partial or complete sclerosis of the cancellous bone, often in the entire skeleton. In the early stage of the disease, the bones are sclerotic only in the metaphyses of the tubular bones, in the peripheral areas of the flat bones; for the rest of these bones, the spongy structure is preserved. Uneven compaction of the skull bones is detected. The accessory cavities are usually sclerotic (to a greater degree – the main and frontal).
The defeat of the jaw bones is accompanied by a violation of the development and teething. The effect of the disease on the teeth is expressed in slowing development, late eruption and change in their structure. The teeth have underdeveloped roots, obliterated tooth cavities and channels. Characterized by high susceptibility of the teeth carious process.

Marble disease is usually manifested in childhood. Frequent family lesions. Symptoms that cause the patient to see a doctor are pain in the limbs, fatigue when walking. Perhaps the development of deformities and the occurrence of pathological fractures of limbs. On examination, the patient does not notice any abnormalities in physical development. X-ray examination reveals that all the bones of the skeleton (tubular, ribs, pelvic bones, base of the skull, vertebral bodies) have a sharply compacted structure. The epiphyseal ends of the bones are somewhat thickened and rounded, the metaphysis is mace-shaped thickened, the external shape and size of the bones are not changed. All bones are dense and completely opaque to X-rays, there is no bone marrow channel, no cortical bone. The bones of the skull base, pelvis, and vertebral bodies are especially sclerosed. In some cases, in the metaphysical parts of the long tubular bones, transverse luminosities are visible, which gives them a marble tint. Bones become less elastic, brittle. Pathological fractures are a common complication of marble disease. Fractures of the femur are more common. Due to the normal state of the periosteum, their healing takes place in the usual terms, but in some cases, consolidation is slowed down due to the disabling of the endosteus from the osteogenesis process, since tissues of the medullary canal are sclerotic. The latter circumstance in childhood is the cause of the development of secondary anemia of the hypochromic type.

The insufficiency of the hematopoietic function of the bone marrow leads to a compensatory increase in the size of the liver, spleen and lymph nodes. The number of leukocytes increases in the blood, and immature forms, normoblasts, appear.

The content of phosphorus and calcium in the blood and urine does not change. Changes as hypochromic anemia are possible. The consequence of changes in the structure of the skeleton are deformations of the facial and cerebral skull, spine, chest. Varus deformity may develop in the proximal femur, the breech-like distortions of the diaphysis of the femur. When a hyperostosis of the skeleton occurs in the first years of life, hydrocephalus develops as a result of osteosclerosis of the skull base; characterized by low growth, late onset of walking, weakening or loss of vision due to squeezing of the optic nerves in the bone canals, late appearance of islands of ossification of the epiphyses, delayed teething, which are often affected by caries.

Diagnosis of Marble Disease

Differential diagnosis of marble disease is carried out with other, more rare diseases, accompanied by hyperostosis, osteopoikilia, melorestosis, Kamurati-Engelmann’s disease. It should be borne in mind that increased sclerosis of individual bones is also observed in lymphogranulomatosis, rickets, osteomyelitis.

Marble Disease Treatment

The best results for the treatment of this disease were obtained in attempts to transplant bone marrow. However, currently there is no really effective therapy for it.

Treatment of marble disease is carried out mainly on an outpatient basis. It is aimed at strengthening the neuromuscular system. Assign remedial gymnastics, swimming, massage. A full nutrition rich in vitamins (fresh vegetables and fruits, cottage cheese, natural fruit and vegetable juices) is recommended. Children are periodically sent for sanatorium treatment. It is not possible to restore normal bone formation processes in clinical conditions, since pathogenetic therapy of marble disease has not yet been developed. With the development of anemia, a complex of pathogenetic measures aimed at its elimination is carried out.

Prevention of Marble Disease

For the prevention of the birth of sick children in families, it is possible to establish the carriers of the disease, as well as prenatal diagnosis of marble disease in the fetus for periods from 8 weeks of pregnancy.

For the prevention and treatment of pathological fractures, bone deformities, dynamic orthopedic observation is necessary. With a significant violation of the function perform corrective osteotomy.