Aplasia medular congénita de serie roja: Anemia de DiamondBlackfan. A propósito de un caso / Marrow aplasia congenital red series: Diamond BlackfanAnemia. About a case

La Aplasia Medular pura de Células Rojas es un trastorno que se caracteriza por anemia con ausencia casi completa de precursores de células rojas en la médula ósea, con contaje de leucocitos y plaquetas normales. La anemia de Diamond-Blackfan es un síndrome de insuficiencia de la médula ósea caracterizada por anemia, reticulocitopenia y disminución de precursores eritroides en la médula ósea. Se presenta el caso de un lactante menor masculino de 2 meses de edad, sin antecedentes familiares ni perinatales de importancia, cuya madre evidencia palidez cutáneo mucosa progresiva asociado a hiporexia; acude a centro de salud donde realizan paraclínicos que reportan hemoglobina en 1,7g/dL. Se realiza frotis de sangre periférica donde se muestra serie eritroide francamente afectada con contaje granulocítico y megacariocítico normales; se realiza biopsia y aspirado de médula ósea concluyéndose aplasia medular de serie roja y en vista de otros hallazgos clínicos, se plantea posible anemia de Diamond-lackfan. Se indica tratamiento con glucocorticoides, sin embargo por respuesta insuficiente, se inicia eritropoyetina aumentando dosis de forma progresiva, a pesar de la administración de la misma, amerita transfusiones sanguíneas de forma regular; se realizan estudios de compatibilidad con familiares de primer grado resultando positivos, actualmente es candidato a trasplante alogénico de médula ósea. Se concluye que a pesar de corresponder a un síndrome poco frecuente, debe sospecharse ante la presencia de anemia severa, sin pérdida sanguínea aguda y descarte previo de otras etiologías, además se plantea que el inicio oportuno del tratamiento es fundamental para la supervivencia de estos pacientes(AU)

Pure red cell aplasia medullary is a disorder characterized by anemia with almost complete absence of red cell precursors in the bone marrow, with leukocyte count and platelets. e Diamond-Blackfan anemia is a failure syndrome characterized by bone marrow anemia, reticulocytopenia and decreased erythroid precursors in the bone marrow. the case of an infant under 2 months of age presented no family or perinatal history major, whose mother progressive skin pallor evidence mucosa associated with hyporexia; go to health center where they perform paraclinical reporting hemoglobin 1.7 g /dL. peripheral blood smear where erythroid frankly affected with normal megakaryocytic granulocytic count shown is made; It biopsied and bone marrow aspirate concluding marrow red cell aplasia; possible anemia Diamond-Blackfan in light of other clinical findings arises. It stays with glucocorticoid treatment, however insufficient response, begins erythropoietin dose progressively increasing, despite it, warrants blood transfusions on a regular basis; compatibility studies performed with firstdegree resulting positive, currently a candidate for allogeneic bone marrow transplantation. It is concluded that despite being a rare syndrome should be suspected in severe anemia where there is acute blood loss, ruling out other etiologies; also timely initiation of treatment is critical to the survival of these patients(AU)

Short Stature in Patients with Diamond-Blackfan Anemia: A Cross-Sectional Study.

OBJECTIVE: To systematically describe the short stature of patients with Diamond-Blackfan anemia and to explore factors affecting the height development of patients with Diamond-Blackfan anemia. STUDY DESIGN: This cross-sectional study was conducted at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and the height, weight, and clinical data of 129 patients with Diamond-Blackfan anemia were collected from June 2020 to September 2020. RESULTS: The median height-age-z score (HAZ) of children affected by Diamond-Blackfan anemia was -1.54 (-6.36-1.96). Short stature was found in 37.98% of the patients. Specific Diamond-Blackfan anemia growth curves were developed for weight, height, and body mass index, separately for male and female patients. Multivariable logistic regression models showed that female sex (aOR 4.92; 95% CI 1.29-18.71; P = .0195), underweight (aOR 10.41, 95% CI 1.41-76.98, P = .0217), cardiovascular malformations (aOR 216.65; 95% CI 3.29-14279.79; P = .0118), and RPL11(aOR 29.14; 95% CI 1.18-719.10; P = .0392) or RPS26 (aOR 53.49; 95% CI 1.40-2044.30; P = .0323) mutations were independent risk factors for short stature. In the subgroup of patients who were steroid-dependent, patients with a duration of steroid therapy over 2 years (OR 2.95; 95% CI 1.00-8.66; P = .0494) or maintenance dose of prednisone >0.1 mg/kg per day (OR 3.30; 95% CI 1.02-10.72; P = .0470) had a higher incidence of short stature. CONCLUSIONS: Patients with Diamond-Blackfan anemia had a high prevalence of short stature. The risk of short stature increased with age and was associated with sex, underweight, congenital malformations, and RPL11 or RPS26 mutations. The duration of steroid therapy and maintenance dose of steroid was significantly associated with the incidence of short stature in steroid-dependent patients with Diamond-Blackfan anemia.

[Deferasirox and Complex Proximal Tubulopathy. Presentation of two clinical cases]. / Deferasirox y Tubulopatía Proximal Compleja. Presentación de dos casos clínicos.

INTRODUCTION: Treatment with iron chelators is essential for patients with iron overload secondary to repeated trans fusions. Deferasirox is the first once-daily oral active iron chelator. As a result, therapeutic adherence has improved, reducing the complications of iron overload, especially heart failure. However, it is not exempt from possible side effects, such as kidney involvement, which is more frequent in children. OBJECTIVE: To report 2 patients with Diamond-Blackfan anemia (DBA) who developed impaired renal function secondary to the administration of Deferasirox. CLINICAL CASES: Case 1. A 15-year-old adolescent diagnosed with DBA undergoing treatment with periodic transfusions and Deferasirox. During an acute gastroenteritis, she developed acute renal failure along with complex proximal tubu- lopathy. Case 2. A 5-year-old boy diagnosed with DBA receiving periodic transfusions and treatment with Deferasirox. He presented polyuria with laboratory abnormalities compatible with acute renal failure and proximal tubular dysfunction. In both cases, they were adequately hydrated and Deferasi rox was temporarily suspended, improving renal function. CONCLUSION: Based on these cases, close monitoring of renal and tubular function, as well as ferritin levels, is recommended in patients recei ving Deferasirox. In the presence of intercurrent processes, adequate hydration should be performed, and an early dose reduction or drug administration interruption should be considered in cases of kidney involvement.

Pearson syndrome in a child transplanted for Diamond-Blackfan anemia. / Síndrome de Pearson en un niño trasplantado debido a anemia de Diamond-Blackfan.

Pearson syndrome (PS), shares a number of overlapping features with Diamond-Blackfan anemia (DBA), including early onset of severe anemia, making differential diagnosis important. Differential diagnosis of DBA and PS is critical, since those with DBA may respond to treatment with steroids, may undergo remission, or may benefit from hematopoietic stem cell transplantation (HSCT). However, patients with PS have a different prognosis, with a very high risk of developing acidosis, metabolic problems, and pancreatic dysfunction, and a shorter life expectancy than those with DBA. Here we present a patient who underwent HSCT for DBA but was subsequently diagnosed with PS after developing some complications.

El síndrome de Pearson (SP) comparte varias características con la anemia de Diamond-Blackfan (ADB), incluida la anemia grave de inicio temprano, por lo que es importante hacer un diagnóstico diferencial. El diagnóstico diferencial de la ADB y el SP es fundamental, ya que los pacientes con ADB podrían responder al tratamiento con corticoesteroides, presentar remisión o beneficiarse del trasplante de células madre hematopoyéticas (TCMH). Sin embargo, los pacientes con SP tienen un pronóstico diferente, con un riesgo muy elevado de acidosis, problemas metabólicos y disfunción pancreática, y una expectativa de vida menor en comparación con aquellos con ADB. En este artículo, presentamos el caso de un paciente sometido a TCMH para la ADB, pero que luego fue diagnosticado con SP tras desarrollar algunas complicaciones.

Síndrome de Pearson en un niño trasplantado debido a anemia de Diamond-Blackfan / Pearson syndrome in a child transplanted for Diamond-Blackfan anemia

El síndrome de Pearson (SP) comparte varias características con la anemia de Diamond-Blackfan (ADB), incluida la anemia grave de inicio temprano, por lo que es importante hacer un diagnóstico diferencial. El diagnóstico diferencial de la ADB y el SP es fundamental, ya que los pacientes con ADB podrían res-ponder al tratamiento con corticoesteroides, presentar remisión o beneficiarse del trasplante de células madre hematopoyéti-cas (TCMH). Sin embargo, los pacientes con SP tienen un pronós-tico diferente, con un riesgo muy elevado de acidosis, problemas metabólicos y disfunción pancreática, y una expectativa de vida menor en comparación con aquellos con ADB. En este artículo, presentamos el caso de un paciente sometido a TCMH para la ADB, pero que luego fue diagnosticado con SP tras desarrollar algunas complicaciones.

Pearson syndrome (PS), shares a number of overlapping features with Diamond-Blackfan anemia (DBA), including early onset of severe anemia, making differential diagnosis important. Differential diagnosis of DBA and PS is critical, since those with DBA may respond to treatment with steroids, may undergo remission, or may benefit from hematopoietic stem cell transplantation (HSCT). However, patients with PS have a different prognosis, with a very high risk of developing acidosis, metabolic problems, and pancreatic dysfunction, and a shorter life expectancy than those with DBA. Here we present a patient who underwent HSCT for DBA but was subsequently diagnosed with PS after developing some complications

Massive iron overload and acute-on-chronic liver failure in a patient with Diamond-Blackfan anaemia: a case report.

BACKGROUND: Genetic anaemias lead us to reflect on the classic 'trolley dilemma', when there are two choices but neither one is satisfactory. Either we do not treat anaemia and the patient suffers from chronic tiredness and fatigue, or we do treat it through blood transfusions, leading to iron overload, which is a quite harmful consequence. CASE PRESENTATION: We present the case of a 34-year-old woman with Diamond-Blackfan anaemia (DBA). Bone marrow stem cell transplantation had not been accessible during her childhood, so she had been submitted to monthly blood transfusions throughout her life, leading to a hepatitis C virus infection (which was treated, achieving a sustained virological response when she was 18 years old), and secondary haemochromatosis. Despite chelation therapy, diffuse iron deposition was occurring in multiple organs, markedly in the heart and liver. Her serum ferritin was higher than 21,000 ng/mL and transferrin saturation reached 102%. When she faced heart decompensation, this congestive condition led to an acute liver injury overlapping pre-existing hepatic fibrosis. She progressed to haemodynamic and hepatic failure, with clinical features of acute-on-chronic liver failure (ACLF). Despite therapeutic optimisation, she died of respiratory insufficiency. An autopsy was performed and revealed the macroscopic and microscopic findings of a massive iron deposition in the liver, heart, lungs, spleen, bone marrow, thyroid and adrenal glands. We found marked advance of liver fibrosis (chronic damage), as well as necrosis of hepatocytes in zone 3 of the Rappaport acinus (acute damage), supporting the hypothesis of ACLF. The main feature responsible for acute liver decompensation seemed to be heart insufficiency. CONCLUSION: This is the first case reporting the sequence: DBA, multiple blood transfusions, secondary haemochromatosis, advanced liver fibrosis, heart failure, ACLF and death. A multidisciplinary team is essential to care for DBA patients, since there is a significant emotional burden related to the disease, which might impair an effective chelation therapy and lead to severe consequences due to iron deposition.

Hematopoietic cell transplantation for Diamond Blackfan anemia: A report from the Pediatric Group of the Brazilian Bone Marrow Transplantation Society.

OBJECTIVES: The aim of this study was to analyze the outcomes of children with Diamond-Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT). METHODS: We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty-five received their first HCT from an HLA-matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD). RESULTS: After a median follow-up of 4 years, estimate 5-year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty-eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD). CONCLUSION: Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher-income countries and international registries.

Importancia del manejo interdisciplinario de pacientes con Fisuras Labiopalatinas y Anemia de Blackfan Diamond. Reporte de caso: seguimiento a 2 años / Importância da abordagem interdisciplinar de paciente com Fissura Labiopalatina e Anemia de Blackfan Diamond: acompanhamento de dois anos / Importance interdisciplinary management of Diamond-Blackfan anemia and Cleft lip and palate sequel: Accompaniment of two years

Las fisuras labiopalatinas (FLP) son las malformaciones craneofaciales congénitas más comunes. La anemia de Diamond-Blackfan o anemia aneritroblástica es una hipoplasia congénita selectiva de la serie roja, asociada a alteraciones cardiacas, renales, malformaciones en manos, hipertelorismo y retraso en el crecimiento. La presentación de las FLP y pacientes con Anemia de Diamond-Blackfan es del 10.3%. Objetivo: Presentar un reporte de caso de un paciente de 12 años con anemia de Diamond-Blackfan y secuela de FLP de la Clínica Interdisciplinaria de LPH de la Pontificia Universidad Javeriana (Bogotá-Colombia) donde el abordaje interdisciplinario, el casomanejo del comportamiento y el apoyo psicológico brindado a la familia fueron fundamentales para lograr la adherencia, clarificar el diagnóstico y obtener los resultados terapéuticos esperados. Resultados: se logró la adherencia al tratamiento y el éxito de éste en apoyo con otras especialidades, permitiendo un seguimiento de 2 años. Conclusiones: El manejo multidisciplinario e interdisciplinario con especialidades odontológicas, médicas, y de la salud en general para el manejo de pacientes con FLP y síndromes asociados, resulta importante para el éxito en el tratamiento.

As fissura labiopalatina são as malformações craniofaciais congênitas mais comuns. A anemia do Diamante-Blackfan ou anemia aneritroblástica seletiva é uma hipoplasia congênita da série vermelha, associada com o coração, rim, malformações mãos, hipertelorismo e distúrbios retardo de crescimento. A apresentação de Fissura labiopalatina e pacientes com anemia do Diamante-Blackfan é de 10,3% dos casos. Objetivo: Apresentar um caso clínico de um paciente de 12 anos com anemia do Diamante-Blackfan e Fissura labiopalatina sequela do Interdisciplinar Clinic LPH da Pontificia Universidad Javeriana (Bogotá Colômbia), onde a abordagem interdisciplinar, gestão de comportamento e apoio psicológico prestado aos família foram fundamentais para alcançar a adesão a esclarecer o diagnóstico e obter os resultados terapêuticos esperados. Resultado: a adesão ao tratamento e seu sucesso no apoio de outras especialidades de saúde alcançados. Conclusões: O tratamento multidisciplinar e interdisciplinar com especialidades odontológicas, médicas e de saúde em geral para o tratamento de pacientes com FLP e síndromes associadas, é importante para o sucesso do tratamento

Cleft lip and palate (CLP) are the most common congenital craniofacial malformations. The Diamond-Blackfan anemia or congenital erythroblastic anemia is a selective red cell hypoplasia associated with heart, kidney, malformed hands, hypertelorism and stunted alterations. The presentation of Cleft lip and palate in patients with Diamond-Blackfan anemia is 10.3% of cases. Aim: To present a case report of a patient of 12 years with Diamond-Blackfan anemia and Cleft lip and palate sequel from the Interdisciplinary Clinic LPH of the Pontificia Universidad Javeriana (Bogota Colombia) where the interdisciplinary approach, behavior management and psychological support provided to the family were instrumental in achieving the expected therapeutic results. Results: Adherence to treatment and its success in supporting other health specialties during two years is slown. Conclusions: The multidisciplinary and interdisciplinary management with dental specialties, medical, and health in general for the management of patients with FLP and associated syndromes, it is important for successful treatment

Anemia de Diamond Blackfan: un diagnóstico de exclusión / Anemia of Diamond Blackfan: an exclusión diagnosis

La anemia de Diamond Blackfan es un trastorno genético y clínico raro, caracterizado por aplasia eritrocitaria, que clásicamente se manifiesta durante el primer año de vida, típicamente a los 2-3 meses de edad. El 25% de los afectados presentan anemia severa en la infancia, normo o macrocitosis, reticulocitopenia y disminución selectiva de células precursoras eritroides en medula ósea. Es causada por mutaciones que afectan genes que codifican para proteínas ribosomales, inicialmente fue identificado RPS19, que codifica la proteína S19 y las mutaciones a otros genes que codifican proteínas ribosomales. Se presenta el caso de una paciente de cuatro meses de edad quien debutó con anemia severa, quien no mejoró con la suplencia de hierro, vitamina B12, y ácido fólico y además fueron descartadas sistemáticamente causas frecuentes de anemia. El diagnóstico de anemia de Diamond Blackfan en nuestro medio es un diagnóstico de exclusión, dada la dificultad para acceso a pruebas de confirmación genética. Se establece el diagnóstico y se da manejo con glucocorticoides con buena respuesta clínica y paraclínica

The Diamond Blackfan anemia is a rare genetic and clinical disorder. It is characterized by red cell aplasia, which typically occurs during the first year of life, typically during the second to the third month of age. 25% of the patients had severe anemia during their childhood, normo or macrocytosis, reticulocyte and selective decrease in the number of erythroid precursor cells in bone marrow. It is caused by mutations affect genes encoding ribosomal proteins, RPS19 initially was identified, which encodes S19 protein and mutations in other genes encoding ribosomal proteins. We present a case of a four-month-old who debuted with severe anemia in whom the substitution were iron supplements, vitamin B12 and folic acid, showed no improvement and who also were systematically discarded as common causes of anemia. The diagnosis of Diamond Blackfan anemia in our country is a diagnosis of exclusion, given the difficulty of access to genetic confirmation tests. In this article the diagnosis is established and gives management with glucocorticoid with good clinical and paraclinical response

The Stomatological Complications of Diamond-Blackfan Anemia: A Case Report.

Diamond-Blackfan Anemia (DBA) is a rare heterogeneous genetic disease characterized by severe anemia, reduction or absence of erythroid progenitors, and pro-apoptoptic hematopoiesis, which culminates in bone marrow failure. The disease generally manifests in infancy, as craniofacial, cardiac, genitourinary, and upper limb congenital anomalies. Therapy with corticoids is the treatment of choice, while blood transfusion is adopted during diagnosis and as a chronic approach if the patient does not respond to corticoids. This case report describes DBA in a patient that presented with lesions on the oral mucosa caused by secondary neutropenia. The stomatologist plays an important role in a transdisciplinary team and must remain attentive to the general health conditions of patients, since some oral lesions may be associated with systemic events.

Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón / Allogenic hematopoietic stem cell transplantation with unrelated cord blood: Report of three cases from the Chilean cord blood bank

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank]. / Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón.

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Diamond-blackfan anemia and growth status: the French registry.

OBJECTIVES: To study the frequency and risk factors of growth retardation (GR) in patients with Diamond-Blackfan anemia. STUDY DESIGN: A cross-sectional survey including the 95 patients followed by hematologists affiliated with the French Society of Pediatric Hematology and Immunology for whom growth data were available; 43 patients were transfusion dependent, 32 were steroid dependent, and 20 patients were off treatment. GR was defined as height below 2 SD. RESULTS: Growth retardation was observed in 29.5% (28) patients. The proportion of GR increased significantly with age (16% <10, 32% among 10 to 16, 47.6% among 17 to 25, 41.7% among >16 years) and was higher in on-treatment than in off-treatment patients (35% among transfusion-dependent, 37% among steroid-dependent vs 5% among off-treatment). GR was significantly linked to associated malformations (OR, 2.3 [1.1 to 8.0]; P = .02) and intrauterine growth retardation (OR, 6.0 [1.1 to 11.6]; P = .021). GR remained independently associated with age, malformations, and treatment in a logistic regression. CONCLUSIONS: Our study showed that the risk of GR increases with age and is associated with treatment dependence. This result addresses the question of the respective part, in the pathogenesis of GR, of the disease severity, illustrated by treatment dependence on the one hand and of the deleterious effects of long-term treatments on the other hand.