Osteopetrosis autosómica dominante benigna: Reporte de caso / Autosomal dominant osteopetrosis: Case report

La osteopetrosis es una enfermedad infrecuente, se caracteriza por el incremento de la densidad ósea observada en las radiografías, resultado de anormalidades en la diferen- ciación y función de los osteoclastos que les incapacita para la resorción ósea y cartilaginosa, formándose huesos más densos, pero más frágiles. Objetivo: describir la Osteopetrosis Auto- sómica Dominante mostrando nuestra experiencia el método de tratamiento. Con un amplio conocimiento de esta patología, los hallazgos radiográficos característicos y los manejos tera- péuticos adecuados podremos lograr un diagnóstico precoz certero y una mejor sobrevida de los pacientes. Reporte de caso: Paciente femenina de 13 años, con historia de fracturas espontáneas a repetición en los antebrazos principalmente, la madre niega antecedentes de trauma; asimismo refiere observar retraso en el crecimiento de la paciente, por lo cual acude al hospital regional de occidente, Quetzaltenango, Guatemala, para evaluación. Se le realizan radiografías en proyección anteroposterior (AP) y lateral de cráneo, de extremidades superio- res e inferiores y de columna dorsal evidenciando en las radiografías de cráneo aumento de la densidad ósea y aumento de grosor de la misma, en la columna dorsal se observó aumento de la esclerosis a nivel de las placas terminales superiores e inferiores de los cuerpos vertebrales, dando la típica apariencia de "vertebra en sándwich", signo patognomónico de esta enferme- dad. La paciente recibió tratamiento con prednisolona, vitamina D y calcio en dosis de acuerdo a las medidas antropométricas de la paciente y control médico por año para evaluar estado clínico...(AU)

Osteopetrosis infantil maligna / Malignant Infantile osteopetrosis

INTRODUCCIÓN: Osteopetrosis Infantil Maligna (OIM) es un grave e inusual desorden genético debi do a una actividad osteoclástica anormal. OBJETIVO: Reportar lactante en quien se documentó una Osteopetrosis Infantil Maligna, revisando aspectos diagnósticos y terapéuticos más relevantes. CASO CLÍNICO: Reportamos un lactante de 10 meses de sexo masculino en quien se confirmó OIM tras presentar plaquetopenia y visceromegalias. En su historial destacó ser primer hijo de padres no consanguíneos, y entre sus hallazgos presentó hepatoesplenomegalia, plaquetopenia y anemia graves, compromiso sensorial visual y auditivo e infecciones a repetición. El diagnóstico fue confirmado mediante estudio genético, el cual identificó 2 mutaciones heterocigotas en el gen TCIRG1. Se rea lizó trasplante de precursores hematopoyéticos, sin haber presentado recuperación hematológica, falleciendo por enfermedad veno oclusiva. DISCUSIÓN: La OIM es una enfermedad inusual, grave y de inicio temprano, siendo necesario un elevado índice de sospecha ante hepatoesplenomegalia y falla medular. El diagnóstico temprano y el trasplante de precursores hematopoyéticos son las únicas intervenciones potencialmente curativas de esta entidad letal.

INTRODUCCIÓN: Malignant Infantile Osteopetrosis (MIOP) is a rare and severe genetic disorder due to abnormal osteoclast activity. OBJECTIVE: To report an infant who presented Malignant Infantile Osteopetrosis, reviewing the most relevant diagnostic and therapeutic aspects. CLINICAL CASE: A ten- month-old male infant with diagnosis of MIOP confirmed after presenting thrombocytopenia and visceromegaly. He was the first child of non-consanguineous parents, and among the findings, he presented severe hepatosplenomegaly, thrombocytopenia, and anemia; visual and hearing impairment, and repeated infections. The diagnosis was confirmed by genetic study, which identified two heterozygous mutations in the TCIRG1 gene. Hematopoietic stem cells were transplanted without hematological recovery. The patient died due to occlusive venous disease. DISCUSSION: MIOP is a rare, severe, and early-onset disease, with a high rate of suspicion necessary in the presence of hepatosplenomegaly and bone marrow failure. Early diagnosis and hematopoietic stem cells transplanta tion are the only potentially therapeutic interventions of this lethal entity.

Autosomal recessive osteopetrosis type I: description of pathogenic variant of TCIRG1 gene / Osteopetrosis infantil maligna: descripción de una nueva mutación patogénica de TCIRG1

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.

Autosomal-dominant osteopetrosis: An incidental finding.

Osteopetrosis is a descriptive term that refers to a group of rare, heritable disorders of the skeleton. Osteopetrotic conditions vary greatly in their presentation and severity, from just as an incidental finding on radiographs to causing life-threatening complications such as bone marrow suppression. It is caused by failure of osteoclast development and function. Osteopetrosis can be inherited as autosomal-recessive, autosomal-dominant or as X-linked traits, with the most severe forms being the autosomal-recessive ones. The severity of the disease is mild to moderate in the autosomal-dominant forms, with normal life expectancy. Diagnosis is largely based on clinical and radiographic evaluation. The present paper reports a case of autosomal-dominant osteopetrosis complicated by osteomyelitis with a short review of the condition.

Assessment of bone density in patients before and after kidney transplantation

Accentuation of bone loss is one of the most important skeletal complications after transplantation. Early diagnosis and treatment of osteopenia and osteoporosis reduce risk of fractures and prevent the aggravation of it by using corticosteroid after kidney transplantation. A total of 50 patients that received graft during the research time, 31 of them completed it. They were screened for decreased bone mineral density at baseline, 6 and 12 months after transplantation with dual-energy x-ray absorptiometry [DEX A] of lumbar spine and hip. A total of 31 patients [17 [55.8%] female and 14 [45.2%] male] with end stage renal disease entered the study. The mean age of patients in both genders were 39.67 +/- 14.5 years [range: 20-67years]. Replacement therapy in 24 patients [77.4%] was hemodialysis and in 7 patients [22.6%] was peritoneal dialysis. Before transplantation, the mean of T-score in femoral neck and lumbar vertebra were -0.88 +/- 1.19 and-0.37 +/- 1.12 respectively, osteopenia was found in 41.9% and 29% of each region. On 6 months after transplantation, the mean of T-score in femoral neck and lumbar vertebra -1.42 +/- 0.95 and -1.41 +/- 1.36 respectively. Incidence of osteopenia in each region was 83.9% and 64.5% in turn. We tried to examine them in the first year after transplantation, the mean of T-score in femoral neck was-1.13 +/- 1.11 and in lumbar vertebra was -1.29 +/- 1.33. After 6 months, bone mass reduction was significant [p<0.05], but there was not any significant difference between 6 and 12 months following transplantation [p>0.05]. Bone loss was highest in the first 6 months after transplantation. Then, treatment was necessary during this period of time

Carbonic anhydrase II deficiency: A novel mutation.

Carbonic anhydrase II (CA II) deficiency is an extremely rare autosomal recessive disorder, characterised by a triad of osteopetrosis, renal tubular acidosis and cerebral calcifications. A 12-year-old boy with classical features of CA II deficiency is reported who was found to be homozygous for the mutation in CA II gene and parents were heterozygous for the same mutation .To the best of our knowledge this is the first case report of mutation proven CA II deficiency from India.

Dental radiographic findings of malignant osteopetrosis: report of four cases

Osteopetrosis is a rare skeletal disorder that results from a defect in the differentiation and function of osteoclasts. The lack of normally functioning osteoclasts results in abnormal formation of the primary skeleton and a generalized increase in the bone mass. This disorder is inherited as an autosomal recessive [osteopetrosis congenita] and an autosomal dominant trait [osteopetrosis tarda]. In this article, we report four cases of malignant osteopetrosis and describe the clinical and dental radiographic findings associated with this rare disease

Osteopetrosis and osteonecrosis in snake Boa constrictor / Osteopetrose e osteocondrose em serpente Boa constrictor

Uma jibóia (Boa constrictor), de onze anos de cativeiro, apresentou à seis meses um histórico de aumento de volume ao longo da coluna vertebral e perda progressiva dos movimentos e de apetite. Exames radiológicos revelaram aumento da opacidade, áreas de excrescências ósseas e inúmeras fraturas ao longo da coluna. Devido o prognóstico desfavorável, a serpente foi eutanasiada. À necropsia, aumento de volume com estenose do canal vertebral e compressão da medula espinhal foram observados, juntamente com fraturas completas de corpos vertebrais. O diagnóstico de osteopetrose e osteonecrose foi firmado à histologia.

Osteopetrose maligna: transplante de medula óssea / Malignant osteopetrosis: bone marrow transplantation

A osteopetrose é uma osteopatia hereditária caracterizada pela deficiência na reabsorção óssea que ocorre por disfunção dos osteoclastos. Com o acúmulo de material osteóide que oblitera o canal medular, ocorre hematopoiese extramedular (hepato-esplenomegalia), obliteração dos forames dos nervos cranianos (cegueira, surdez, paralisias faciais), macrocefalia, protusão da fronte, hipertelorismo, exoftalmo, aumento da pressão intracraniana, retardo na erupção dentária, atraso no crescimento, atraso no desenvolvimento neuropsicomotor, e a morte ocorre precocemente nos primeiros anos de vida. A única alternativa terapêutica curativa é o transplante de medula óssea (TMO) de doador HLA idêntico, pois restabelece a hematopoiese e a função monócito-macrófago, com melhora das lesões ósseas e anormalidades hematopoiéticas, embora não reverta as alterações sensoriais já instaladas. Os autores relatam casos de duas crianças portadoras de osteopetrose maligna submetidas ao transplante de medula óssea com sucesso. A primeira encontra-se no dia +1260 do TMO, com melhora evidente da radiologia esquelética, sem progressão das deficiências neurológicas que apresentava, e com biópsia óssea sem sinais de osteopetrose. O segundo paciente encontra-se no dia + 700, com sinais de reabsorção óssea e sem progressão dos danos neurológicos. Os autores chamam a atenção para a necessidade de diagnóstico precoce da osteopetrose e o rápido encaminhamento para o transplante de medula óssea antes da instalação de seqüelas neurológicas definitivas.

Osteopetrosis is an inherited disorder characterized by the inability to reabsorb and remodel bone due to osteoclast dysfunction. The encroachment by bone and mineralized cartilage of the medullary cavities leads to extramedullary hematopoiesis (hepatosplenomegaly) and cranial-nerve foramina leads to blindness, auditory nerve damage, and occulomotor and facial nerve palsies. Defective bone re-absorption also leads to macrocephaly, frontal bossing, hypertelorism, exophthalmos, increased intracranial pressure, retarded tooth eruption, retarded linear growth and psychomotor delay. Death occurs within the first years of life. The only curative therapy is allogeneic bone marrow transplantation with a HLA-identical donor, which restores hematopoiesis, monocyte-macrophage function and bone recovery, but there is no sensorial deficit restoration once present. The authors report two cases of allogeneic bone marrow transplant for infantile malignant osteopetrosis. The first child, on day 1260 after bone marrow transplantation (BMT), showed radiologic bone recovery and no progression of neurological deficits with a bone biopsy showing no signs of osteopetrosis. The second child showed signs of bone re-absorption and no progression of neurological deficits on day 700. The authors emphasize the importance of early diagnosis of osteopetrosis and the necessity of bone marrow transplantation before neurological deficits have begun.

Osteopetrosis / Osteopetrosis

Se describe el caso de un paciente de 37 años de edad con diagnóstico de osteopetrosis del adulto. Clínicamente se presentó con gran decaimiento, cansancio fácil, palidez cutaneomucosa y ausencia de visceromegalia. Los exámenes de laboratorio revelaron anemia moderada, linfocitosis relativa, eritrosedimentación acelerada, valores químicos sanguíneos dentro de límites normales, así como también los de calcio y fósforo; punciones sin material medular y dureza pétrea del hueso, todo lo cual, apoyado en resultados de otras pruebas, justificó que se iniciase tratamiento con prednisona y ácido fólico, cuya ejecución garantizó el logro de una mejoría clínica y hemática.

The case of a 37 year-old patient is described with diagnosis of adult's osteopetrosis. Clinically he presented with a great weakness, easy fatigue, mucocutaneous pallor and visceromegaly absence. The laboratory tests revealed moderate anemia, relative lymphocytosis, accelerated erythrosedimentation, blood and chemical values within the normal limits, as well as those of calcium and phosphorus; punctions without medullary material and stone hardness of the bone; all these, supported by the results of other tests, justified that treatment with prednisone and folic acid could be applied. The treatment guaranteed the achievement of a clinical and hematic improvement.

[Frequency of osteoporosis and osteopenia in Post-Menopausal Military family's women]

Osteoporosis is a major and growing public health problem in bone sexes but particularly in Post-Menopausal women.The aim of this study is evaluation of T Score and BMD mean in vertebra and femoral neck for estimation of Frequency of osteopenia and osteoprosis in post-menopausal women of military families, which had not other secondary osteoporosis risk factors. In a cross sectional study we studied 200 post menopausal women that were not menopause more than 5 years and had not secondary cause of osteoporosis. Lumbar vertebra and femoral neck bone density measured by DEXA [Norland ZR-63, for Atkinson, WI, USA] system. Mean age of patients was 57.2 +/- 4/2 and T Score mean in lumbar spines and femoral neck was-1.09 +/- 1.11 and -1.69 +/- 1.05 respectively. Frequency of osteoporosis was 25.5% and 7% and osteopenia was seen in 51% and 47.5% respectively. Over all, osteoporosis Frequency was 26% and osteopenia Frequency was 52.5% respectively. This study showed post menopausal osteoporosis is most common in military families same another research and according to high prevalence of postmenopausal osteoporosis that induces mortality and morbidity and high treatment cost and long term health cares, the human community needs to comprehensive studies about prevention, causes, prevention and treatment of osteoporosis

Post operative diagnosis of osteopetrosis.

Osteopetrosis is a rare hereditary disease that was first described by a German Albert Schonberg in 1904. At least five types of osteopetrosis have been described. Among them osteopetrosis congenita (autosomal recessive) and osteopetrosis tarda (autosomal dominant) are most common. Here we are reporting a case of osteopetrosis tarda, who is a female of fifty years of age presented with fracture femur. Preoperatively there was no suspicion of osteopetrosis.She was only suspected while introducing an IM Nail during her fracture reduction. Diagnosis of osteopetrosis was confirmed post operatively by histopathology of medullary cavity of her femur.

Amaurose bilateral por osteopetrose congênita: relato de caso e revisäo da literatura / Bilateral amaurosis due to congenital osteopetrosis: case report and literature review

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.

Osteopetrose: relato de caso / Osteopetrosis: case report

A osteopetrose é raro distúrbio do metabolismo ósseo, de caráter hereditário, que pode apresentar muitas manifestaçöes clínicas e achados radiológicos característicos. Entre as alteracöes clínicas mais frequentes encontram-se fraturas patológicas, dores ósseas e neuropatia cranianas. Apresentamos, a seguir, o relato do caso de uma paciente com diagnóstico de osteopetrose em sua forma dominante

Osteopetrose / Osteopetrosis

A osteopetrose é um raro distúrbio do metabolismo ósseo, de caráter hereditário, que pode apresentar várias manifestaçöes clínicas e achados radiológicos característicos. Dentre os distúrbios clínicos mais frequentes se encontram fraturas patológicas, dores ósseas e neuropatias cranianas. Apresentamos a seguir o relato de uma paciente com diagnóstico de osteopetrose em sua forma dominante.