RESUMEN
ABSTRACT: Pyruvate kinase (PK) is a key enzyme in glycolysis, the sole source of adenosine triphosphate, which is essential for all energy-dependent activities of red blood cells. Activating PK shows great potential for treating a broad range of hemolytic anemias beyond PK deficiency, because they also enhance activity of wild-type PK. Motivated by observations of sickle-cell complications in sickle-trait individuals with concomitant PK deficiency, activating endogenous PK offers a novel and promising approach for treating patients with sickle-cell disease.
Asunto(s)
Anemia Hemolítica Congénita no Esferocítica , Anemia de Células Falciformes , Piruvato Quinasa/deficiencia , Errores Innatos del Metabolismo del Piruvato , Humanos , Anemia Hemolítica Congénita no Esferocítica/tratamiento farmacológico , Anemia Hemolítica Congénita no Esferocítica/etiología , Eritrocitos , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/complicacionesRESUMEN
We describe a 21-month-old male with relapsed clear cell sarcoma of the kidney receiving enteral nutrition who experienced recurrent, ketotic hypoglycemia. During relapse therapy, he had recurrent hypoglycemia episodes, in the setting of hematochezia and diarrhea. Evaluation revealed low carnitine levels. He received supplementation with oral levocarnitine throughout the remainder of treatment, resulting in normalization of serum carnitine levels and no further hypoglycemia. We believe adverse effects of the chemotherapy on his single kidney and gastrointestinal insult resulted in hypoglycemia and carnitine deficiency. Our case highlights that carnitine deficiency should be considered when acute onset hypoglycemia without obvious cause occurs.
Asunto(s)
Cardiomiopatías , Hiperamonemia , Hipoglucemia , Desnutrición , Carnitina/deficiencia , Carnitina/uso terapéutico , Niño , Humanos , Hiperamonemia/complicaciones , Hipoglucemia/inducido químicamente , Hipoglucemia/tratamiento farmacológico , Lactante , Masculino , Desnutrición/complicaciones , Enfermedades MuscularesRESUMEN
BACKGROUND: Medical affirmation, including gender-affirming hormones, is an essential component in the treatment of many transgender and gender-diverse youth. The risk of venous thromboembolism (VTE) during testosterone therapy for gender-affirming care is not fully elucidated. OBSERVATION: The case describes a 17-year-old transgender male treated with testosterone therapy who presented with an occlusive deep vein thrombosis of right axillary and subclavian veins. Testosterone level was 920 ng/dL at the time of the deep vein thrombosis, and he had no risk factors for VTE. A complete hypercoagulable workup was negative. CONCLUSIONS: The possibility of testosterone therapy as a risk factor for VTE may suggest the need to include this information during informed consent discussions. Long-term anticoagulation may be considered for those restarting testosterone therapy.
Asunto(s)
Personas Transgénero , Transexualidad , Tromboembolia Venosa , Trombosis de la Vena , Adolescente , Humanos , Masculino , Testosterona/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Trombosis de la Vena/tratamiento farmacológicoRESUMEN
Skewed drug metabolism of 6-mercaptopurine (6-MP) can jeopardize antileukemic effects and result in toxicities during the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Allopurinol can alter 6-MP metabolism to maximize therapeutic effects while reducing toxicities. Over 75% of our patients with acute lymphoblastic leukemia or lymphoblastic lymphoma experienced a 6-MP-related toxicity. Review of metabolite date a showed 6-methylmercaptopurine nucleotide levels were >10,000 in 55% of the cohort, suggesting 6-MP shunting. Allopurinol was initiated in 12 of 23 shunters with resolution of toxicities. We propose an algorithm to incorporate allopurinol into chemotherapy regimens for patients with inappropriate 6-MP metabolism.
Asunto(s)
Algoritmos , Alopurinol/farmacología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Linfoma no Hodgkin/tratamiento farmacológico , Mercaptopurina/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Antimetabolitos , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/metabolismo , Niño , Preescolar , Quimioterapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/patología , Masculino , Mercaptopurina/efectos adversos , Mercaptopurina/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
The development of inhibitors toward factor VIII (FVIII) is a common and serious complication of hemophilia A (HA) therapy. Patients with hemophilia who develop inhibitors often undergo time- and resource-intensive immune tolerance induction (ITI) protocols. We report a 15-month-old male with severe HA and a high-titer inhibitor that occurred while receiving prophylactic treatment with recombinant FVIII (rFVIII), in whom significant inhibitor titer reduction was achieved with thrice weekly infusions of a new, prolonged half-life rFVIII-Fc fusion protein product (trade name Eloctate). Further studies are warranted to explore the potential of Eloctate in ITI protocols.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/inmunología , Desensibilización Inmunológica , Factor VIII , Hemofilia A/tratamiento farmacológico , Tolerancia Inmunológica/efectos de los fármacos , Receptores Fc , Factor VIII/administración & dosificación , Factor VIII/antagonistas & inhibidores , Factor VIII/genética , Factor VIII/inmunología , Hemofilia A/inmunología , Humanos , Lactante , Masculino , Receptores Fc/administración & dosificación , Receptores Fc/genética , Receptores Fc/inmunología , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunologíaRESUMEN
6-Mercaptopurine (6-MP) is the mainstay of treatment for acute lymphoblastic leukemia and lymphoblastic lymphoma. It is metabolized into the pharmacologically active, 6-thioguanine nucleotide (6-TGN), and 6-methyl mercaptopurine nucleotides (6-MMPN), which is associated with hepatotoxicity that jeopardizes antileukemic therapy. Allopurinol alters the metabolism of 6-MP to increase 6-TGN levels and decreases 6-methyl mercaptopurine nucleotides levels. We report 2 cases in which combination therapy of allopurinol with 6-MP was used successfully to avoid hepatotoxicity while delivering adequate 6-TGN levels. We suggest that this combination therapy can be used safely to change the metabolite production in patients who develop excessive hepatotoxicity.