Medical Journal of Dr. D.Y. Patil Vidyapeeth

: 2013  |  Volume : 6  |  Issue : 2  |  Page : 184--187

Infantile malignant osteopetrosis: A case report of three siblings

Sahil Jain, Vineeta Pande, Geeta R Karambelkar, Sharad R Agarkhedkar 
 Department of Pediatrics, Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India

Correspondence Address:
Sahil Jain
Resident, Department of Paediatrics, Dr. D. Y. Patil Medical College, Pune - 411018


Infantile malignant osteopetrosis, a rare hereditary, generalized disorder of bone characterized by a significant increase in the density of the skeletal tissues is described in three siblings. The incidence, genetic etiology, clinical, laboratory, radiological features, management and prognosis have been discussed.

How to cite this article:
Jain S, Pande V, Karambelkar GR, Agarkhedkar SR. Infantile malignant osteopetrosis: A case report of three siblings.Med J DY Patil Univ 2013;6:184-187

How to cite this URL:
Jain S, Pande V, Karambelkar GR, Agarkhedkar SR. Infantile malignant osteopetrosis: A case report of three siblings. Med J DY Patil Univ [serial online] 2013 [cited 2021 Oct 16 ];6:184-187
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Osteopetrosis is a rare hereditary, generalized disorder of bone characterized by a significant increase in the density of the skeletal tissues usually manifesting in two basic forms: An autosomal dominant benign form (osteopetrosis tarda) and an autosomal recessive malignant form (osteopetrosis congenita). Here we present case of infantile familial malignant osteopetrosis in a 5-year-old child with similar illness in his two siblings with different presentation.

 Case Reports

Case 1

A 5-year-old male child presented with complaints of fever, cough and weakness for last 5 days to OPD. On enquiring parents told that he is also having disfigurement of face on right side and distension of abdomen for last 2 years. He had been transfused blood twice within last 4 years.

His milestones were delayed. There was history of recurrent respiratory infections. He was the second product of third degree consanguineous marriage. On general examination, the patient was thin built, short statured. Examination revealed that he was pale,had frontal bossing and grade II PEM. There was generalized lymphadenopathy. Early loss of deciduous teeth and caries of teeth were noted. He had abdominal distension with huge hepatosplenomegaly [Figure 1]b. On examination of respiratory system he had findings suggestive of bronchopneumonia. Nervous system examination revealed right-sided facial nerve paresis [Figure 1]a without evidence of any other neurological deficit. Fundus examination was normal. On investigations he had anemia with hemoglobin 5.6 gm%,TLC - 4200, PCV 20%, and platelet count 32000. Peripheral smear was suggestive of microcytic hypochromic cells with reduced platelets. X-rays showed the thick bones with increased bone density [Figure 1]c-e.{Figure 1}

Bone marrow examination revealed few osteoclasts and osteoblasts, occasional erythroid and myeloid cells with abnormal bone trabeculae with osteoid and cartilage.

Diagnosis of osteopetrosis was confirmed.

Case 2

A 2-year-old female child, sibling of the above case presented with complaints of progressive blindness and weakness. General examination revealed pallor and frontal bossing. There was no evidence of lymphadenopathy and edema. Examination of abdomen revealed hepatosplenomegaly [Figure 2]a. {Figure 2}Examination of respiratory, cardiovascular and nervous system was within normal limits. Fundus examination revealed bilateral optic atrophy. On investigations she had anemia with hemoglobin 6.4 gm%, TLC - 3800, PCV 23%, and platelet count of 46000. Peripheral smear suggestive of microcytic hypochromic cells with reduced platelets. X-rays showed the thick bones with increased bone density [Figure 2]b.

Case 3

Third sibling (eldest) died at the age of 3 years and had similar complaints such as progressive weakness, abdominal distension and progressive blindness and the history of recurrent respiratory tract infections. She was not investigated.


The infantile malignant form (autosomal recessive) has an incidence of 1 in 250,000 births, with a particularly high incidence reported in Costa Rica 3.4:100,000. [1],[2] Mutations in CLCN7 and TCIRG1 are responsile for this form. Mutations in the PLEKHM1 gene cause milder forms of autosomal recessive osteopetrosis. [3] Moreover 75% of the patients with infantile osteopetrosis die before the age of six, many of recurrent infections, especially pneumonia, or osteomyelitis complicated by septicemia.

It is characterized by widespread osteopetrosis, a characteristic heavy head with frontal bossing, hypertelorism, hepatosplenomegaly, psychomotor delay, failure to thrive, dental problems, osteomyelitis of mandible, [4] deafness and blindness. Other manifestations are anemia, [5] infections, sensory disorders and fractures.

Deafness and blindness are generally thought to represent effects of pressure on nerves. [6],[7] The anemia is caused by encroachment of bone on marrow, resulting in obliteration, and the hepatosplenomegaly is caused by compensatory extramedullary hematopoiesis. The condition results from defective resorption of immature bone.

Osteopetrosis tarda (autosomal dominant) usually presents during childhood or adolescence with fractures, mild anemia and less frequently cranial nerve dysfunction, dental abnormalities or osteomyelitis of mandible.

Carbon Anhydrase Type II (CAII) Deficiency [8] is caused by defect in gene responsible for producing CAII on chromosome 8 (at 8q22). Symptoms include increased bone density, a tendency to fracture easily and changes in body chemistry. Other symptoms may include intracranial calcifications, sensorineural hearing loss and developmental delays. The blood is slightly acidic and has a high chloride concentration (hyperchloremic acidosis). The blood acidity is caused by excessive leakage of bicarbonate from the kidney tubules.


Laboratory Findings

Serum calcium - It generally reflects oral intake; hypocalcemia can occur and cause rickets if it is severe.Parathyroid hormone (PTH) - It is often elevated (secondary hyperparathyroidism).Acid phosphatase - It is raised due to increased release from defective osteoclasts.Creatinine kinase isoform BB (CK-BB) - Its levels are raised due to increased release from defective osteoclasts.


Radiological features of osteopetrosis are usually diagnostic. Patients usually have generalized osteosclerosis. [9] Bones may be uniformly sclerotic, but alternating sclerotic and lucent bands may be noted in iliac wings and near the ends of long bones (Rugger-Jersey Sign). [1] The bones may be clublike or may have the appearance of a bone within bone (endobone). Radiographs may also show evidence of fractures or osteomyelitis.

Bone Marrow Biopsy

Bone biopsy is not essential for diagnosis, because radiographs usually are diagnostic. Histomorphometric studies of bone may be useful to predict the likelihood that BMT will succeed. Patients with crowded bone marrow are less likely than others to respond to a transplant.


Calcitriol [10] -It appears to help by stimulating dormant osteoclasts, thus stimulating bone resorption. Large doses of calcitriol, along with restricted calcium intake, sometimes improve osteopetrosis dramatically. However, calcitriol usually produces only modest clinical improvement, which is not sustained after therapy is discontinued.

Recombinant human interferon β-treatment with β-interferon has produced long-term benefits. It improves white blood cell function, greatly decreasing the incidence of new infections. With treatment, trabecular bone volume substantially decreases and bone marrow volume increases. This results in increases in hemoglobin, platelet counts, and survival rates. [11]

Bone marrow transplantation-Bone marrow transplantation markedly improves some cases of infantile osteopetrosis. [12],[13] It can cure bone marrow failure and metabolic abnormalities in patients whose disease arises from an intrinsic defect of the osteoclast lineage.

It is the only curative treatment for this disease. However, it may be limited to a subset of patients whose defects are extrinsic to the osteoclast lineage and whose condition is unlikely to respond.

Surgical Treatment

In pediatric osteopetrosis, surgical treatment is sometimes necessary because of fractures. The constellation of problems associated with this condition and the prevailing opinions regarding their management have been reviewed. [14]


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