A Case Report of Malignant Infantile Osteopetrosis
A two month-old male infant was referred to the department of pediatric gastroenterology of Sisli Etfal Education and Research Hospital because of hepatosplenomegaly and thrombocytopenia. Past medical history of the patient revealed that he was hospitalized in the first day of his life in the neonatal unit because of poor feeding. Sepsis work up was done. He received ampicilin-gentamycin therapy empirically. In the follow up hypocalcemia and intracranial hemorrhage were observed. The patient was referred to our clinic for further investigation of hepatosplenomegaly and thrombocytopenia.\nHe was born after an uncomplicated pregnancy and delivery in the 38th gestational week according to Ballard. Birth weight was 2600 gr. Apgar score was 7/9. Parental consanguinity was significant in the past medical history. One son and one daughter of the family died in infancy period with unknown etiologies.\nSystemic examination revealed hepatomegaly with the liver noted to be 4/3 cm, splenomegaly with the spleen noted to be 3 cm. The patient had a bulging anterior fontanel with 4×4 cm in size. His weight was 3.4 kg (<3rd percentile), his height was 44 cm (<3rd percentile) and head circumference of the patient was 38 cm (50-75 percentile). He had pale appearance and fundoscopic examination showed optic atrophy bilaterally.\nLaboratory examination yielded the following: hemoglobin 11.4 g/dl; white blood cell count 4400 cells/mm3 and platelet count 24.000/mm3. Biochemical analysis was normal except for AST 118 U/L, LDH 1150 U/L, parathyroid hormone (PTH) 349 pg/mL, alkaline phosphatase (ALP) 847 IU/L, acid phosphatase 16.4 U/L. Peripheral blood smear was significant for leukoerytroblastosis (). Arterial blood gas analysis was normal. Serology for toxoplasma, rubella, cytomegalovirus, herpes, and hepatitis virus was negative. Immunoglobulin (G, M, A) levels, lymphocyte subsets, urine and serum amino acid and urine organic acid analyses were also normal. Tandem mass spectrophotometry showed no abnormality.\nAbdominal ultrasonography detected a marked hepatosplenomegaly. Cranial ultrasonography showed ventriculomegaly of the lateral and third ventricles. A computed axial tomographic scan of orbits demonstrated the narrowing of the optic foramina bilaterally. Bone marrow aspiration showed hypocellularity. Bone marrow culture was negative. Liver biopsy demonstrated extra-medullary hematopoiesis, and ballooning of parancymal cells were significant. Skeletal survey revealed diffuse sclerosis of all bones. Visual evoked potentialisation and brain-stem evoked response examination were planned.\nOur initial diagnosis was congenitally acquired infection (TORCH) or a kind of storage disease (like lipid storage or lysosomal diseases) but physical examination and laboratory results confirmed the diagnosis of osteopetrosis. The disease was presented in newborn period and two children of the family had died. The absence of any metabolic acidosis with an alkaline urine pH and the absence of any cerebral calcifications excluded a diagnosis of carbonic anhydrase II deficiency syndrome. Familial erytrophagocytic lympho-histiocytosis and familial histoplasmosis were also considered in the differential diagnosis. Peripheral blood smear, bone marrow aspiration and culture findings and liver biopsy findings did not support the diseases.\nThe patient was referred for hematologic stem cell transplantation (SCT). He had two available HLA matched donors in his family who were patient's older sisters. He was taken to the stem cell transplantation program, but unfortunately blindness developed in the patient. He was still in follow-up 10 months after the diagnosis.