Albers schonberg disease (osteopetrosis ) in a young adult – a rare case report.

INTRODUCTION

Osteopetrosis is a disorder that includes impaired osteoclasts function or absent osteoclasts. It is also known as osteopetrosis tarda or marble bone disease. The cells that resorb bone was first described in 1904 by Heinrich Albers – Schonberg. The name was given by Karshner in 1926.^1,2 Hence it is called as Albers – Schonberg’s disease. It is a group of rare hereditary skeletal disorders characterized by a marked increase in bony density due to defect in remodeling caused by the failure of normal osteoclast function.³ In healthy bone, a steady state is achieved in which the production of bone by cells called osteoblasts is balanced by bony resorption by osteoclasts. The dysfunctional osteoclasts that are observed in osteopetrosis result in bony overgrowth, leading to bones that are abnormally dense and brittle. The estimated prevalence is one in 1, 00, 000 – 5, 00, 000.³

Several forms of osteopetrosis exist, generally it is sub divided into autosomal dominant adult form (benign) is associated with few or no symptoms ^3-5, whereas autosomal recessive infantile form (malignant) if untreated, is typically fatal during infancy or early childhood.^3,4,6 A rarer autosomal recessive (intermediate) form presents during childhood with some signs and symptoms of malignant osteopetrosis.⁷ The most commonest is benign form osteopetrosis usually develops later in life and is less severe. Approximately, half of the patients are asymptomatic and the diagnosis is made incidentally or is based on family history. Many patients have bone pain and are fragile, might fracture easily. Other manifestations include visual impairment and psychomotor retardation. Physical findings are related to bony defects and include short stature, frontal bossing, a large head, and hepatosplenomegaly.⁸

The most severe form of marble bone disease is termed as infantile (malignant) osteopetrosis present at birth or develops in early childhood, adolescence, or young adult life. The disease is severe and debilitating. Patients have symptoms of neurologic and hematological derangements, optic atrophy, severe anemia, blindness, deafness, and multiple fractures of the long bones with resulting deformity, hepatosplenomegaly, facial palsy, hydrocephalus, possible mental retardation and osteomyelitis.8 Increased bone density of cortical bone and club – shaped appearance of the long bones may be discovered incidentally on x- rays. ^9,10 This form is also called malignant osteopetrosis, not because of a relationship to cancer but because of the severity of the disease.^6,11

This disorder is inherited in an autosomal recessive pattern, which signifies that both parents are unaffected carriers. When these parents have children, the chance that a particular child will have the disease is one in four.^6,11

Infants with marble bone disease have early loss of vision and also have hearing losses. Because osteoclasts are absent or dysfunctional, the bone marrow cavity in which blood cells are produced does not form normally. A severe form of marble bone disease with manifestations in the new born and a progressive course leading to death at an early age is called osteopetrosis with precocious manifestations.⁶

Most forms of osteopetrosis are transmitted as autosomal traits. The gene for adult Osteopetrosis has been mapped to chromosome 1p2.1.1.² The pathogenesis of all true forms of Osteopetrosis involves diminished osteoclast mediated skeleton resorption. The number of osteoclasts is often increased but they fail to function normally, bone is not resorbed.³ This defective osteoclastic bone resorption, along with continued bone formation and endochondral ossification, leads to cortical bone thickening and cancellous bone sclerosis.

Clinical Features: Initial signs of Infantile Osteopetrosis include normocytic anemia with hepatosplenomegaly and increased susceptibility to infections due to granulocytopenia. In the absence of treatment patient may die during their first decade of life from hemorrhage, pneumonia, severe anemia or sepsis may result from osteomyelitis. Few patients may develop hydrocephalus and sleep apnea. Facial deformity, fracture of the jaw during tooth extraction may also occur without undue force. Teeth are of defective quality, enamel hypoplasia, microscopic dentinal defects and arrested root development, retardation of tooth eruption due to the sclerosis of bone all having been reported.3,1³ In case of Intermediate Osteopetrosis affected patients are short stature and are often asymptomatic at birth, but frequently exhibit fractures by the end of their first decade of life.⁴ Marrow failure and hepatosplenomegaly are rare.5 Some present with cranial nerve deficits, macrocephaly, mild or moderately severe anemia and ankylosed teeth.⁴

In adult form of Osteopetrosis, manifestations are seen later in life and are less severe. The axial skeleton usually shows significant sclerosis, long bones have minimal or no defects. Bone pain frequent in symptomatic patients. Radiographs show an increased radiopacity of medullary bone.³

There are two major adult types exist.³ In one type, cranial nerve compression commonly seen but fractures are rare: whereas, in another type nerve compression is uncommon and fractures are frequent. Osteomyelitis is the complication can occur after tooth extraction, if the mandible is involved.

Treatment and Prognosis: Adult osteopetrosis associated with long term survival as this form of the disease is mild. However, the prognosis for infantile Osteopetrosis without therapy is usually poor, with most of those affected dying in their first decade of life.³ Treatment strategies include correcting anemia, and thrombocytopenia, and treating infections. Bone marrow transplantation and splenectomy may be useful in some patients.³ Optimal transplants require donor marrow from a sibling. Other therapies include Corticosteroids to increase red blood cells and platelets.^3,4 Complications of osteopetrosis can be reversed or prevented in early life by bone marrow transplantation.¹⁴ Clinical studies have shown that regular administration of interferon-gamma1b often in combination with calcitriol has been shown significantly slow the progression of the disease and reduce infection rates.¹⁵

Case Report

A 14 year old male patient visited Department of Pedodontics and preventive dentistry, with a chief complaint of bleeding from the gingiva in relation to lower left back region since one week.

On clinical examination the following observations were made. Dolichocephalic head, exophthalmos, frontal bossing (Figure–1), hypertelerism, depressed nasal bridge, hypoplastic maxilla, mandibular prognathism and the patient was partially mentally disabled. The physical status of the patient was poor (Figure–2). The oral findings showed swollen gingiva in relation to 24, 74, mobility in relation to 74, deep palatal vault, spacing between teeth and multiple impacted teeth.

Past medical reports revealed that, patient had repeated bleeding from the nose, chest infections on and off, diminision of vision, fever, cough, depressed nasal bridge, micrognathia, short fingers, flat fleet, pigeon chest deformity, distended abdomen, (Figure–3) enlarged spleen, shifted trachea towards left. Active movements of the boy were restricted because of diminision of vision as reported by family members.

Blood investigation reports showed following readings. Hemoglobin - 4.3gm; Packed cell volume - 20%; Reticulocyte count – 4.0%; White blood cells - 7600 cells / cu.mm; Polymorphs - 27%; Lymphocytes – 52%; Monocytes – 01%; Eosinophils – 20%; Coagulation time - 04 min; Bleeding time - 03 min.

Patient was diagnosed as suffering from Microcytic hypochromic anemia with eosinophilia. Radiological findings showed generalized increase in bone density (chalky white). Skull vault showed dense bone with narrowing of skull base. Enlarged cardia and skull (Figure – 4, 5, 6).

DISCUSSION

The benign form appears later in life and is less severe. The severe form is invariably fatal in early life and seen in infancy or develops in early childhood.^3,4,6 The osteopetrosis results from a generalized accumulation of bone mass that is secondary to a defect in bone resorption. This defect prevents the normal development of marrow cavities, the normal tubulation of long bones, and the enlargement of osseous foramina 16. In our case evaluation boy was suffering from infantile (malignant) osteopetrosis, there was no evidence of osteopetrosis in family members examined. Symptoms started after first year of life. Patient had repeated bleeding from the nose, diminision of vision, chest infection on and off, severe anemia, hepatosplenomegaly and elongated head. The radiographs showed generalized increase in bone density of the (Chalky white), skull and cardiac enlargement (Figure–6, 7). Loria-Cortes et.al and Nussey reported cases of osteopetrosis due to consanguineous marriages 6. Tips and lynch found frequent affection of siblings on their study while parents were unaffected.¹⁷ Enell and Pehrson have also analyzed the pedigree chart of 3 cases of osteopetrosis born of consanguineous marriages.¹⁸ The role of consanguinity in osteopetrosis still remains hypothetical. Although parents may be consanguineous, this malignant osteopetrosis is sporadic and seldom familial, nor are milder variants found in the same family. The severity of the disease status in children in terms of hematological problems, fragility of bones in terms of incidence of fracture and chance of the next issue being similarly affected needs to be evaluated.

With available information from the family sources that the boy is no more now and passed away at the of 17 years, he was from a low socio economic group family. He had two elder brothers and none of them was suffering from any of the disorders.

CONCLUSION

Osteopetrosis is a rare congenital disorder. Special attention should be given to patients with this disorder due to fragile bone status resulting from defects in osteoclast function and impaired wound healing. Preventive measures must be continuously and vigorously maintained. Early diagnosis and treatments like controlling infections and bone marrow transplantations should be carried out in these children to prevent further serious complications. Every effort should be made to avoid extractions in this high risk group of patients.