RESUMO
Background: Autosomal malignant osteopetrosis is a rare condition arising from dysfunction of bone-resorbing osteoclasts, in which diagnosis requires a high suspicion index. Treatment of choice is allogeneic stem cell transplantation. Best outcomes occur if the procedure is carried out before damage to cranial nerves ensues; nonetheless, patients improve their clinical condition. Case report: An 8-month-old infant was referred for hematology consultation for cytopenias, hepatomegaly, and growth failure. Autosomal malignant osteopetrosis was diagnosed on the basis of physical findings, alteration in calcium and phosphorus metabolism, and hyperdensity of bone. DNA was obtained from the patient and parents; compound heterozygosity of the TCIRG1 gene with a previously non-described deletion (c.1809_1818del) was identified. Conclusions: A new pathogenic mutation of TCIRG1 was identified in a Mexican osteopetrotic patient. Hematopoietic stem cell transplantation was offered as the best available treatment but declined by the parents. An early recognition and wider access to this procedure should be implemented.
Introducción: La osteopetrosis infantil maligna es una condición rara cuyo origen es la deficiente reabsorción ósea por parte de los osteoclastos. Su diagnóstico requiere un alto índice de sospecha. El tratamiento de elección es el trasplante alogénico de células hematopoyéticas. Los mejores desenlaces ocurren si el procedimiento se lleva a cabo antes de que ocurra daño a los nervios craneales. Caso clínico: Paciente masculino de 8 meses de edad fue referido a la consulta de hematología por citopenias, hepatomegalia y falla para crecer. Se diagnosticó osteopetrosis infantil maligna basándose en los hallazgos de la exploración física, la alteración del metabolismo del calcio y el fósforo y la hiperdensidad del hueso. Se obtuvo ADN del paciente y ambos padres; se demostró un heterocigosidad compuesta del gen TCIRG1 con una deleción (c.1809_1818del) no descrita previamente. Conclusiones: Una nueva mutación patogénica de TCIRG1 se identificó en un paciente mexicano con osteopetrosis. Se ofreció trasplante de células progenitoras hematopoyéticas como el mejor tratamiento disponible, pero fue rechazado por los padres. Se necesita un reconocimiento temprano y la implementación del acceso generalizado a este procedimiento.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Osteopetrose/congênito , ATPases Vacuolares Próton-Translocadoras/genética , Humanos , Lactente , Masculino , México , Mutação , Osteopetrose/diagnóstico , Osteopetrose/genética , Osteopetrose/terapia , Deleção de Sequência , Recusa do Paciente ao TratamentoRESUMO
Abstract Background: Autosomal malignant osteopetrosis is a rare condition arising from dysfunction of bone-resorbing osteoclasts, in which diagnosis requires a high suspicion index. Treatment of choice is allogeneic stem cell transplantation. Best outcomes occur if the procedure is carried out before damage to cranial nerves ensues; nonetheless, patients improve their clinical condition. Case report: An 8-month-old infant was referred for hematology consultation for cytopenias, hepatomegaly, and growth failure. Autosomal malignant osteopetrosis was diagnosed on the basis of physical findings, alteration in calcium and phosphorus metabolism, and hyperdensity of bone. DNA was obtained from the patient and parents; compound heterozygosity of the TCIRG1 gene with a previously non-described deletion (c.1809_1818del) was identified. Conclusions: A new pathogenic mutation of TCIRG1 was identified in a Mexican osteopetrotic patient. Hematopoietic stem cell transplantation was offered as the best available treatment but declined by the parents. An early recognition and wider access to this procedure should be implemented.
Resumen Introducción: La osteopetrosis infantil maligna es una condición rara cuyo origen es la deficiente reabsorción ósea por parte de los osteoclastos. Su diagnóstico requiere un alto índice de sospecha. El tratamiento de elección es el trasplante alogénico de células hematopoyéticas. Los mejores desenlaces ocurren si el procedimiento se lleva a cabo antes de que ocurra daño a los nervios craneales. Caso clínico: Paciente masculino de 8 meses de edad fue referido a la consulta de hematología por citopenias, hepatomegalia y falla para crecer. Se diagnosticó osteopetrosis infantil maligna basándose en los hallazgos de la exploración física, la alteración del metabolismo del calcio y el fósforo y la hiperdensidad del hueso. Se obtuvo ADN del paciente y ambos padres; se demostró un heterocigosidad compuesta del gen TCIRG1 con una deleción (c.1809_1818del) no descrita previamente. Conclusiones: Una nueva mutación patogénica de TCIRG1 se identificó en un paciente mexicano con osteopetrosis. Se ofreció trasplante de células progenitoras hematopoyéticas como el mejor tratamiento disponible, pero fue rechazado por los padres. Se necesita un reconocimiento temprano y la implementación del acceso generalizado a este procedimiento.
Assuntos
Humanos , Lactente , Masculino , Osteopetrose/congênito , Transplante de Células-Tronco Hematopoéticas , ATPases Vacuolares Próton-Translocadoras/genética , Osteopetrose/diagnóstico , Osteopetrose/genética , Osteopetrose/terapia , Recusa do Paciente ao Tratamento , Deleção de Sequência , México , MutaçãoRESUMO
OBJECTIVE: Malignant osteopetrosis (MO) is a rare hereditary disease that affects young children. Its physiopathology is explained by a basic defect in osteoclast precursor cells, with a radiographic image of diffuse sclerosis and increased bone density. The bone contains an increased number of structurally abnormal osteoclasts. Infections commonly occur because the neutrophils exhibit reduced chemotactic response and decreased ability of bacterial phagocytosis. PATIENT: A white female patient aged 9 months, of mixed descent, was diagnosed at birth as having MO after bone marrow biopsy. Dental examination revealed the presence of four teeth, all of which had enamel hypoplasia and no carious lesions. After bone marrow transplantation (BMT), an erythematous lesion appeared on the alveolar ridge on day 2, with signs of tooth exfoliation. On day 7, there was gingival bleeding, edema, and erythema at the region of the maxillary incisors with grade 3 mobility, without changes in food intake. RESULTS: Concerning the oral cavity, the patient maintained grade 1 tooth mobility without tooth exfoliation or other oral alterations. CONCLUSION: Accurate diagnosis and careful therapeutic planning are important to avoid the secondary complications of the disease.
Assuntos
Osteopetrose/congênito , Osteopetrose/terapia , Transplante de Medula Óssea , Terapia Combinada , Consanguinidade , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Osteopetrose/diagnóstico por imagem , RadiografiaRESUMO
A osteopetrose congênita é uma rara desordem genética autossômica recessiva caracterizada por osso esclerótico associado a anormalidades hematológicas e neurológicas. Os autores fazem revisäo da literatura e relatam um caso de uma criança do sexo feminino com 2 anos e 5 meses de vida apresentando amaurose bilateral por osteopetrose congênita.
Assuntos
Humanos , Feminino , Pré-Escolar , Cegueira/etiologia , Osteopetrose/congênito , Osteopetrose/complicações , Osteopetrose/diagnósticoRESUMO
This study reports on the developmental status of 23 children, ranging in age from 2 weeks to 11 years, with the severe form of autosomal recessive osteopetrosis. Results revealed widely scattered cognitive, adaptive, and language scores and delayed gross motor skills.