RESUMEN
Hepatitis-associated aplastic anemia (HAAA) accounts for 4% of autoimmune hepatitis in children. An episode of seronegative autoimmune hepatitis is followed a few days or months later by aplastic anemia or full aplasia. This autoimmune disease could be due to a regulation defect in the immune response to a viral trigger, in a genetically predisposed individual. Other causes of hepatitis or aplastic anemia have to be ruled out. Steroids and azathioprine usually control the liver damage but do not prevent the development of aplastic anemia. Aplastic anemia is treated with either hematopoietic stem cell transplantation in patients with a sibling donor or anti-thymocyte globulins and cyclosporine. We propose guidelines to explore and treat this rare disease. We emphasize on the necessary close collaboration between hepatologists and hematologists.
Asunto(s)
Anemia Aplásica , Trasplante de Células Madre Hematopoyéticas , Hepatitis Autoinmune , Niño , Humanos , Anemia Aplásica/complicaciones , Anemia Aplásica/terapia , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/terapia , Ciclosporina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , HermanosRESUMEN
Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.
Asunto(s)
Huesos/patología , Colestasis/genética , Diarrea/genética , Pérdida Auditiva/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación con Pérdida de Función/genética , Adolescente , Animales , Preescolar , Diarrea/fisiopatología , Familia , Femenino , Fibroblastos/patología , Motilidad Gastrointestinal , Humanos , Recién Nacido , Linfocitos/patología , Masculino , Linaje , Fenotipo , Síndrome , Adulto Joven , Pez CebraRESUMEN
BACKGROUND: Familial hypercholesterolaemia is a well-known disorder, but clinical diagnoses tend to be delayed. Acute coronary syndrome may occur in childhood. CASE SUMMARY: Our patient, a young boy with homozygous familial hypercholesterolaemia, complained of persistent chest pain at rest and suffered a non-ST-elevation myocardial infarction (NSTEMI). The diagnosis of NSTEMI was made on the basis of his clinical features, dynamic electrocardiogram changes, troponin elevation, and cardiac computed tomography findings. The patient was managed surgically by intrathoracic artery (ITA) bypass graft. During post-operative follow-up, the young patient suffered from angina pectoris from unexpected and exceptional atheroma stenosis on the ITA. DISCUSSION: Familial hypercholesterolaemia needs to be identified quickly in young patients and lipid lowering therapies should be started without delay.