Clinical and imaging features of malignant infantile osteopetrosis

Abstract

Tfifha M, Gaha M, Gamaoun W, Chemli J, Mabrouk S, Hassayoun S, Zouari N, Jemni H, Abroug S. Clinical and imaging features of malignant infantile osteopetrosis. Turk J Pediatr 2017; 59: 452-457. Human osteopetrosis is a rare genetic disorder caused by osteoclast failure. It encompasses a group of highly heterogeneous forms, ranged widely in severity. Patients with autosomal recessive osteopetrosis are the most severely affected osteopetrotic patients. Here we describe Tunisian children with severe phenotype. They are native from the same geographic region, born to consanguineous parents. Clinical features were cranio-facial dysmorphy, macrocephaly, hepatosplenomegaly, severe anemia and thrombocytopenia with precocious onset of neuronopathic complications, blindness and deafness. Retinal atrophy, reported in a minority of forms is highlighted. Skeletal radiographs revealed generalized increase in bone density and abnormal metaphyseal remodeling, and superimposed rickets resulting from the defect in osteoclasts to provide a normal Ca/P balance. We report an exceptional association with congenital hypothyroidism. Multi-organ failure due to sepsis is one the most severe complications observed. The issue was fatal without hematopoietic stem cell transplantation.

Multiple oral sinus tract and trismus leading to a surprising diagnosis of osteopetrosis: Case report

“…The mainstay of diagnosis largely depends on the radiographic appearance of the skeleton and the clinical progress of the disease . 14,15 In this case report, CT of the chest and pelvis was performed, which revealed the absence of marrow spaces and hepatosplenomegaly. Bone scintigraphy also revealed a lack of bone marrow distribution, exclusion of possible fracture sites, and identified abnormal sites of increased metabolic activity 12 .…”

“…12 Other common features include nystagmus, tooth eruption defects, severe dental caries, frontal bossing, exophthalmus, nasal congestion, neurological abnormalities, skeletal fractures, and osteomyelitis. 14 Osteomyelitis of the jaws is a recognized complication of osteopetrosis that occurs almost exclusively in the mandible instead of the maxilla, demonstrating a thin cortical bone and rich collateral blood supply. 8 It is generally developed as a result of tooth extraction or pulp necrosis.…”

Haploidentical haematopoietic stem cell transplantation for malignant infantile osteopetrosis and intermediate osteopetrosis: a retrospective analysis of a single centre

“…The balance between osteoclasts and osteoblasts is very important for maintaining bone homeostasis. When osteoclasts are dysfunctional, a series of clinical manifestations may arise, such as short stature, fractures, osteomyelitis, hypocalcaemia, convulsions, and neurological lesions [13]. Defective osteoclast activity can Fig.…”

“…In the present study, the clinical symptoms were significantly improved and no aggravation of nervous system involvement was observed after transplantation. Therefore, we postulate that these patients should still undergo HSCT if the disease occurs early with typical clinical manifestations [13,26]. Furthermore, if patients have RANKL gene mutations, HSCT is not recommended because abnormalities in the gene may impede osteoclast maturation [27].…”

Haploidentical Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis and Intermediate Osteopetrosis:A Retrospective Analysis of a Single-Center

“…When osteoclasts were dysfunction, a series of clinical manifestations may arise, such as short stature, fractures, osteomyelitis, hypocalcemia, convulsions, neurological lesions and so on. When the increased bone invades the bone marrow space, bone marrow failure will appear and progress gradually 12 . Defective osteoclast activity can be caused by mutations in genes affecting osteoclast development (such as RANK, RANKL), and function (such as TCIRG1, SNX10, CLCN7, OSTM1).…”