Leukoerythroblastosis, causes: space-occupying lesion in bone marrow including malignancy, fibrosis, storage disorders; infection, severe blood loss, etc.
Further workup:
Imaging study shows diffuse sclerotic bone changes.
Bone marrow aspirate shows no gaucher cells.
Further workup:
Imaging study shows diffuse sclerotic bone changes.
Bone marrow aspirate shows no gaucher cells.
Molecular test: IVS14-1G>A
mutation was detected in the TCIRG1 gene.
Diagnosis: Infantile malignant osteopetrosis
Rare autosomal recessive. congenital disorder of bone resorption characterized by generalized skeletal densification.
Incidence: 1/200 000 live births.
Pathogenesis: Failure of osteoclasts to reabsorb immature bone leading to narrow bone marrow cavity and bone marrow failure.
Presentation: Bone marrow failure, fractures and visual impairment, present in early infancy or in fetal life. Hepatosplenomegaly due to compensatory extramedullary hematopoiesis. cranial nerve (especially optic nerve) compression due to impaired bone remodeling.
HistoPathology: persistence of the primary spongiosa characterized by cores of calcified cartilage within bone. Abnormal presence of primary, woven bone prone to fracture.
Molecular genetics:
Over 50% of cases are due to mutations in the TCIRG1 gene, 10% are due to mutations in the CLCN7 gene. A small number with mutations in the OSTM1 gene.
Diagnosis: clinical and radiological features establish the diagnosis. A bone biopsy may be confirmatory.
Management: Families- genetic counselling, prenatal diagnosis- ultrasound, molecular diagnosis.
Patients may require blood transfusions, treatment for infections and management of their developmental and visual problems.
Bone marrow transplant can alleviate many problems of the disease, perform early with better prognosis.
Diagnosis: Infantile malignant osteopetrosis
Rare autosomal recessive. congenital disorder of bone resorption characterized by generalized skeletal densification.
Incidence: 1/200 000 live births.
Pathogenesis: Failure of osteoclasts to reabsorb immature bone leading to narrow bone marrow cavity and bone marrow failure.
Presentation: Bone marrow failure, fractures and visual impairment, present in early infancy or in fetal life. Hepatosplenomegaly due to compensatory extramedullary hematopoiesis. cranial nerve (especially optic nerve) compression due to impaired bone remodeling.
HistoPathology: persistence of the primary spongiosa characterized by cores of calcified cartilage within bone. Abnormal presence of primary, woven bone prone to fracture.
Molecular genetics:
Over 50% of cases are due to mutations in the TCIRG1 gene, 10% are due to mutations in the CLCN7 gene. A small number with mutations in the OSTM1 gene.
Diagnosis: clinical and radiological features establish the diagnosis. A bone biopsy may be confirmatory.
Management: Families- genetic counselling, prenatal diagnosis- ultrasound, molecular diagnosis.
Patients may require blood transfusions, treatment for infections and management of their developmental and visual problems.
Bone marrow transplant can alleviate many problems of the disease, perform early with better prognosis.