Dyskeratosis congenita: natural history of the disease through the study of a cohort of patients diagnosed in childhood.

Background: Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time. Material and methods: Multicenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020). Results: Fourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3-18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2-24 years]. Six patients died, the median age was 13 years [range, 6-24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6-32 years]. None of them have developed myeloblastic syndrome or cancer. Conclusions: DC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential.

“Doctora, me ha salido un huevo en la cabeza”. A propósito de dos casos / “Doctor, I have a bump on my head. Two cases”

El granuloma eosinófilo es un tipo de histiocitosis de células de Langerhans que afecta exclusivamente al hueso. Puede ser uni o multifocal, siendo la forma unifocal la más habitual. El cráneo es el hueso más afectado en niños, y es más frecuente en niños que en niñas, entre los 5 y 10 años. La radiografía convencional es el método diagnóstico más usado visualizando imágenes osteolíticas características de esta patología, aunque se precisa de una confirmación histológica para realizar el diagnóstico definitivo. Se describen dos casos de granuloma eosinófilo (AU)

Eosinophilic granuloma is a Langerhans cell histiocytosis of the bone. Presentacion of eosinophilic granuloma with a single (monostotic) bone lesion is more common than multiple (polyostotic) bone lesions. The most commonly involved bone is the skull in children. In childhood presentations, prevalence is greater in males and it is most common in children 5 to 10 years of age. Conventional radiograpshs have served as the primary imaginng method used to identify LCH lesions. Histologic confirmation is necessary for the diagnosis. (AU)

Capillary electrophoresis and mutational images of hemoglobin sendagi [Β42 (CD1) PHE → VAL; HBB: C.127T→G].

We report two cases of hemoglobin Sendagi in a Romanian family residing in Spain: a four-year-old boy and his mother, who had been previously diagnosed with another type of congenital hemolytic anemia and had undergone splenectomy in her country during childhood. The unstable hemoglobin variant, hemoglobin Sendagi, is characterized by decreased oxygen affinity caused by replacement of one of the critical amino acid residues, phenylalanine beta 42 (CD1) of the beta-chain, with valine in the heme pocket, resulting in methemoglobin formation. As a result of migratory movements in Europe, new disease-causing hemoglobin variants are emerging in our country. Here, capillary electrophoresis enabled the identification of the variant and a molecular study was used to establish an accurate diagnosis.

Neuropatías y moda en la adolescencia: presentación de 2 casos clínicos / Neuropathy and style in adolescence: Presentation of two cases

Introducción: Las neuropatías localizadas adquiridas, no posquirúrgicas ni postraumáticas (excluida la afectación de pares craneales), son raras en la infancia. Se presentan 2 casos clínicos de adolescentes con neuropatía periférica secundaria a fenómenos compresivos en relación con hábitos estéticos. Casos clínicos: El caso 1 corresponde a una niña de 13 años con neuropatía del ciático poplíteo externo; presenta una pérdida ponderal en un breve periodo de tiempo y practica ejercicio físico intenso a diario. El caso 2 corresponde a una niña de 14 años con meralgia parestésica del nervio femorocutáneo; habitualmente viste pantalones elásticos ajustados. Conclusiones: Ambos casos presentan neuropatías periféricas debido a fenómenos compresivos, favorecidos por la pérdida de peso, el ejercicio físico y el uso de ropa ajustada; ponen de manifiesto los peligros de algunos hábitos estéticos y relacionados con la moda y pueden ocultar otras patologías subyacentes, como trastornos de la conducta alimentaria. El tratamiento conservador es efectivo en la mayoría de los casos, pero en casos refractarios puede desarrollarse una discapacidad, por lo que es importante su identificación precoz (AU)

Introduction: Acquire neuropathies with different post-surgical or post-traumatic etiology (excluding cranial nerves affection) are uncommon in children. Two cases of peripherical neuropathy in teenagers caused by compressive phenomenon as a consequence of aesthetic habits are presented. Clinical cases: Case 1: a 13 year old patient with external popliteal sciatic neuropathy. An important weight loss in few months is referred associated with intense physical activity. Case 2: a 14 year old patient with meralgia paresthetica. She usually wears 'skinny jeans'. Conclusions: Both cases present peripheral neuropathies in teenagers, due to compressive phenomenons, increased by diet, weight loss and tight-fitting clothes. These cases remind us the dangerous effect of aesthetic habits and fashion which can hide important diseases like alimentary disorders. Conservative treatment is effective in most cases, but an early diagnosis is needed because of the important disability they can cause in some refractory cases (AU)

Immunotherapy with liposome-bound TRAIL overcomes partial protection to soluble TRAIL-induced apoptosis offered by down-regulation of Bim in leukemic cells

Purpose. Human Apo2-Ligand/TRAIL secreted by natural killer cells and cytotoxic T lymphocytes plays an important role immunosurveillance controlling tumor growth and metastasis. Moreover, the fact that Apo2L/TRAIL is capable of inducing cell death in tumor cells but not in normal cells makes this death ligand a promising anti-tumor agent. Previous data from our group demonstrated that Apo2L/TRAIL was physiologically released as transmembrane protein inserted in lipid vesicles, called exosomes. Recently, we demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) resembling the natural exosomes, greatly improved Apo2L/TRAIL activity and were able to induce apoptosis in hematological malignancies. In this study, we have deepened in the underlying mechanism of action of LUV-TRAIL in hematologic cells. Methods/patients. Cytotoxic ability of LUV-TRAIL was assessed on Jurkat cells either over-expressing the anti-apoptotic protein Mcl1 or down-regulating the pro-apoptotic protein Bim previously generated in our laboratory. We also tested LUV-TRAIL cytotoxic ability against primary human leukemic cells from T-cell ALL patient. Results. Silencing Bim but not Mcl-1 over-expression partially protects Jurkat cells from apoptosis induced by sTRAIL. LUV-TRAIL induced caspase-8 and caspase-3 activation and killed Jurkat-Mcl1 and Jurkat-shBim more efficiently than sTRAIL independently of the mitochondrial pathway. On the other hand, LUV-TRAIL were clearly more cytotoxic against primary leukemic cells from a T-cell ALL patient than sTRAIL. Conclusion. Tethering Apo2L/TRAIL to the surface of lipid nanoparticles greatly increases its bioactivity and could be of potential use in anti-tumor therapeutics (AU)

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Immunotherapy with liposome-bound TRAIL overcomes partial protection to soluble TRAIL-induced apoptosis offered by down-regulation of Bim in leukemic cells.

PURPOSE: Human Apo2-Ligand/TRAIL secreted by natural killer cells and cytotoxic T lymphocytes plays an important role immunosurveillance controlling tumor growth and metastasis. Moreover, the fact that Apo2L/TRAIL is capable of inducing cell death in tumor cells but not in normal cells makes this death ligand a promising anti-tumor agent. Previous data from our group demonstrated that Apo2L/TRAIL was physiologically released as transmembrane protein inserted in lipid vesicles, called exosomes. Recently, we demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) resembling the natural exosomes, greatly improved Apo2L/TRAIL activity and were able to induce apoptosis in hematological malignancies. In this study, we have deepened in the underlying mechanism of action of LUV-TRAIL in hematologic cells. METHODS/PATIENTS: Cytotoxic ability of LUV-TRAIL was assessed on Jurkat cells either over-expressing the anti-apoptotic protein Mcl1 or down-regulating the pro-apoptotic protein Bim previously generated in our laboratory. We also tested LUV-TRAIL cytotoxic ability against primary human leukemic cells from T-cell ALL patient. RESULTS: Silencing Bim but not Mcl-1 over-expression partially protects Jurkat cells from apoptosis induced by sTRAIL. LUV-TRAIL induced caspase-8 and caspase-3 activation and killed Jurkat-Mcl1 and Jurkat-shBim more efficiently than sTRAIL independently of the mitochondrial pathway. On the other hand, LUV-TRAIL were clearly more cytotoxic against primary leukemic cells from a T-cell ALL patient than sTRAIL. CONCLUSION: Tethering Apo2L/TRAIL to the surface of lipid nanoparticles greatly increases its bioactivity and could be of potential use in anti-tumor therapeutics.

Disfunción autonómica paroxística desde el periodo neonatal y meduloblastoma / Paroxysmal autonomic dysfunction of neonatal onset and medulloblastoma

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