A Case Report of Malignant Infantile Osteopetrosis Case Report

Home , Osteopetrosis, Pseudohypoparathyroidism

Iran J Pediatr Case Report Sep 2012; Vol 22 (No 3), Pp: 421-424

A Case Report of Malignant Infantile Osteopetrosis

Merve Usta1, MD; Seda Geylani Gulec2, MD; Serap Karaman3, MD; Ela Erdem*2, MD; Hicran Emral2, MD, and Nafiye Urgancı1, MD

1. Department of Pediatric Gastroenterology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey 2. Department of Pediatrics, Sisli Etfal Education and Research Hospital, Istanbul, Turkey 3. Department of Pediatric Hematology, Sisli Etfal Education and Research Hospital, Istanbul, Turkey Mar 16, 2011 Aug 15, 2011 Nov 12, 2012

Received: ; Final Revision: ; Accepted: Abstract Background:

Malignant infantile osteopetrosis (MIOP) presents early in life with extreme sclerosis of the skeleton and reduction of bone marrow spaces. Since there is a defect in the bone marrow, the disease can cause anemia, extramedullary hematopoiesis secondary to anemia leading to hepatosplenomegaly, cranial nerves compression and severe growth failure. This disorder is often lethal within the first decade of life becauseCase Presentation of secondary: infections. Stem cell transplantation (SCT) remains the only curative therapy. We report a two-month old male infant, diagnosed as MIOP while investigating the cause ofConclusion: hepatosplenomegaly. The patient was referred for stem cell transplantation. Malignant infantile osteopetrosis should be kept in mind as a rare cause of hepatosplenomegaly and the patient should be referred for stem cell transplantation before neurologic or visual impairment IraniandevelopJournals. of Pediatrics, Volume 22 (Number 3), September 2012, Pages: 421-424

Key Words:

Osteopetrosis; Infant; Hepatomegaly; Splenomegaly Introduction

auditory, and facial nerves. Increased bone density also obliterates the medullary cavity, leading to Malignant infantile osteopetrosis (MIOP) is an extramedullary hematopoiesis, hepatospleno- autosomal recessive disorder characterized by megaly, anemia, and thrombocytopenia. Growth reduced activity of osteoclasts, resulting in retardation[1] and recurrent infections are also generalized bone osteosclerosis. Abnormal common . The disease is fatal in infancy and is osteoclast activity paired with normal bone cured with hematopoietic stem cell transplantation, with a rate of success by 50% and formation by osteoblasts leads to the[1] development of densely sclerotic fragile bones . The disease unsatisfactory[3 ] rescue of growth and visual presents in the first few months of life with the deterioration . In this article, we report a two-month old boy, manifestations relating to underlying[2] defect in osteoclastic bone resorption . Overgrowth of who presented with hepatosplenomegaly and cranial nerve foramina results in nerve thrombocytopenia in newborn period and is compression, which frequently affects the optic, diagnosed as infantile malignant osteopetrosis * Corresponding Author; Address: Ihlamurkuyu mah. Agaoglu my town sitesi A6 blok Da:1-2, Ümraniye/İstanbul E-mail: [email protected]

. which is a rare cause of hepatosplenomegaly and Immunoglobulin (G, M, A) levels, lymphocyte thrombocytopenia subsets, urine and serum amino acid and urine organic acid analyses were also normal. Tandem mass spectrophotometry showed no abnormality. Abdominal ultrasonography detected a marked Case Presentation hepatosplenomegaly. Cranial ultrasonography showed ventriculomegaly of the lateral and third ventricles. A computed axial tomographic scan of A two month-old male infant was referred to the orbits demonstrated the narrowing of the optic department of pediatric gastroenterology of Sisli foramina bilaterally. Bone marrow aspiration Etfal Education and Research Hospital because of showed hypocellularity. Bone marrow culture was hepatosplenomegaly and thrombocytopenia. Past negative. Liver biopsy demonstrated extra- medical history of the patient revealed that he was medullary hematopoiesis, and ballooning of hospitalized in the first day of his life in the parancymal cells were significant. Skeletal survey neonatal unit because of poor feeding. Sepsis work revealed diffuse sclerosis of all bones. Visual up was done. He received ampicilin-gentamycin evoked potentialisation and brain-stem evoked therapy empirically. In the follow up hypocalcemia response examination were planned. and intracranial hemorrhage were observed. The Our initial diagnosis was congenitally acquired patient was referred to our clinic for further infection (TORCH) or a kind of storage disease investigation of hepatosplenomegaly and (like lipid storage or lysosomal diseases) but thrombocytopenia. physical examination and laboratory results He was born after an uncomplicated pregnancy confirmed the diagnosis of osteopetrosis. The and delivery in the 38th gestational week disease was presented in newborn period and two according to Ballard. Birth weight was 2600 gr. children of the family had died. The absence of any Apgar score was 7/9. Parental consanguinity was metabolic acidosis with an alkaline urine pH and significant in the past medical history. One son and the absence of any cerebral calcifications excluded one daughter of the family died in infancy period a diagnosis of carbonic anhydrase II deficiency with unknown etiologies. syndrome. Familial erytrophagocytic lympho- Systemic examination revealed hepatomegaly histiocytosis and familial histoplasmosis were also with the liver noted to be 4/3 cm, splenomegaly considered in the differential diagnosis. Peripheral with the spleen noted to be 3 cm. The patient had blood smear, bone marrow aspiration and culture a bulging anterior fontanel with 4×4 cm in size. findings and liver biopsy findings did not support His weight was 3.4 kg (<3rd percentile), his height the diseases. was 44 cm (<3rd percentile) and head The patient was referred for hematologic stem circumference of the patient was 38 cm (50-75 cell transplantation (SCT). He had two available percentile). He had pale appearance and HLA matched donors in his family who were fundoscopic examination showed optic atrophy patient’s older sisters. He was taken to the stem bilaterally. cell transplantation program, but unfortunately Laboratory examination yielded the following: blindness developed in the patient. He was still in hemoglobin 11.4 g/dl; white blood cell count 4400 follow-up 10 months after the diagnosis. 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 Discussion IU/L, acid phosphatase 16.4 U/L. Peripheral blood smear was significant for leukoerytroblastosis (Fig. 1). Arterial blood gas analysis was normal. Osteopetrosis is a family of bone diseases

Serology for toxoplasma, rubella, cytomegalovirus, characterized by[4] osteoclast failure and impaired herpes, and hepatitis virus was negative. bone resorption . It has three forms which are: Iran J Pediatr, Vol 22 (No 3); Sep 2012 423

Fig. 1:

Leukoerytroblastosis is significant in peripheral blood smear of the patient

autosomal recessive, autosomal dominant and X- was present in three of six cases. In our case optic linked inheritance. Autosomal Recessive atrophy was found bilaterally in the early days of Osteopetrosis (ARO) may have the most severe his life. course. Having an incidence of 1:250,000 in Radiologic findings showed increased bone general population, ARO is more frequent in density with defective metaphyseal remodeling. certain ethnic groups, including inhabitants of The “bone within-bone” [5] appearance is

Costa-Rica in whom the incidence[5] is much higher characteristic and diagnostic . Computerized than elsewhere (3.4:100,000) . tomography scan can be used for diagnosis and to

Infantile, or malignant, osteopetrosis is present determine the effect of the treatment. It [9 is] also at birth[5 ] or develops within the first months of used to assess auditory and optic canal . The infancy . Our patient had the signs and symptoms skeletal survey and CT scan of the patient was from the first day of his life. specific for radiologic findings of osteopetrosis. Abnormal bone formation and fibrous tissue Differential diagnoses include congenital replace the bone marrow space and finally disorders (e.g., pseudohypoparathyroidism, hematopoesis is decreased. Extramedullar pyknodysostosis, and hypoparathyroidism), hematopoesis occurs resulting in leukoerythro- chemical poisoning (e.g., lead, fluoride, and blastic anemia and thrombocytopenia. Liver and beryllium), malignancies (myeloproliferative[5] spleen enlarge progressively. Hemolysis resulting diseases and leukemia), and sickle cell disease . from hypersplenism[1,6] worsens the anemia and Based on clinical history and radiographic thrombocytopenia . Our case was referred for findings, our case was accepted as the infantile or hepatosplenomegaly and peripheral blood smear malignant type, with autosomal recessive was significant for leukoerytroblastosis and he inheritance. Familial histoplasmosis was excluded needed transfusions for anemia also for because bone marrow culture was negative and thrombocytopenia before liver biopsy. Liver peripheral blood smear and liver biopsy findings biopsy of the patient demonstrated signs of did not support the disease. extramedullary hematopoiesis. Stem cell transplantation (SCT) is the only Visual impairment results from bony curative therapy for patients with MIOP, and it encroachment on the optic[7] foramina. It is a should be performed as soon as the diagnosis is common initial symptom . Optic atrophy is also made because neurologic impairment occurs in present in a significant number [8 of] cases. In the early infancy and will become irreversible even series reported by Phadke et al , optic atrophy after successful SCT. Successful results have been 424 Malign Infantile Osteopetrosis; M Usta, et al

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