ABSTRACT
OBJECTIVES: Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected. CASE PRESENTATION: Mutation analysis revealed one unreported pathogenic variant in the TCN2 gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment. CONCLUSIONS: This is the first report of Argentinean patients with TC deficiency that detected a new variant in TCN2. NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Anemia, Macrocytic , Vitamin B 12 Deficiency , Infant, Newborn , Humans , Vitamin B 12/therapeutic use , Transcobalamins/genetics , Retrospective Studies , Vitamin B 12 Deficiency/diagnosis , Vitamin B 12 Deficiency/drug therapy , Vitamin B 12 Deficiency/genetics , Amino Acid Metabolism, Inborn Errors/drug therapy , Early DiagnosisABSTRACT
Las hemoglobinopatías son trastornos genéticos que afectan a la molécula de hemoglobina (Hb). Las mutaciones en las cadenas a o b que alteran el tetrámero de Hb pueden modificar la capacidad de la molécula para unirse al oxígeno. Las hemoglobinopatías con baja afinidad al oxígeno pueden presentarse con cianosis y una lectura alterada de la oximetría de pulso, lo que lleva a pruebas innecesarias y, a veces, invasivas para descartar afecciones cardiovasculares y respiratorias. En el siguiente reporte de caso, presentamos a una paciente pediátrica, asintomática, que se presentó a la consulta por detección de desaturación en oximetría de pulso. Las pruebas de laboratorio iniciales mostraron una anemia normocítica, normocrómica. Las muestras de gas venoso demostraron una p50 elevada. Después de extensas herramientas de diagnóstico, se diagnosticó una variante de Hb con baja afinidad al oxígeno, Hb Denver.
Hemoglobinopathies are genetic disorders that affect the hemoglobin (Hb) molecule. Mutations in the alpha or beta chains altering the Hb tetramer may modify the molecule's oxygen-binding capacity. Hemoglobinopathies with low oxygen affinity may occur with cyanosis and an altered pulse oximetry reading, leading to unnecessary and sometimes invasive tests to rule out cardiovascular and respiratory conditions. In the case report described here, we present an asymptomatic pediatric patient who consulted for desaturated pulse oximetry. Her initial laboratory tests showed normocytic, normochromic anemia. Venous blood gas samples showed an elevated p50. After using extensive diagnostic tools, a variant of Hb with low oxygen affinity was diagnosed: Hb Denver.
Subject(s)
Humans , Female , Child , Hemoglobins, Abnormal/analysis , Hemoglobins, Abnormal/genetics , Hemoglobins, Abnormal/chemistry , Hemoglobinopathies/diagnosis , Hemoglobinopathies/genetics , Anemia , Oxygen , OximetryABSTRACT
Hemoglobinopathies are genetic disorders that affect the hemoglobin (Hb) molecule. Mutations in the alpha or beta chains altering the Hb tetramer may modify the molecule's oxygen-binding capacity. Hemoglobinopathies with low oxygen affinity may occur with cyanosis and an altered pulse oximetry reading, leading to unnecessary and sometimes invasive tests to rule out cardiovascular and respiratory conditions. In the case report described here, we present an asymptomatic pediatric patient who consulted for desaturated pulse oximetry. Her initial laboratory tests showed normocytic, normochromic anemia. Venous blood gas samples showed an elevated p50. After using extensive diagnostic tools, a variant of Hb with low oxygen affinity was diagnosed: Hb Denver.
Las hemoglobinopatías son trastornos genéticos que afectan a la molécula de hemoglobina (Hb). Las mutaciones en las cadenas a o b que alteran el tetrámero de Hb pueden modificar la capacidad de la molécula para unirse al oxígeno. Las hemoglobinopatías con baja afinidad al oxígeno pueden presentarse con cianosis y una lectura alterada de la oximetría de pulso, lo que lleva a pruebas innecesarias y, a veces, invasivas para descartar afecciones cardiovasculares y respiratorias. En el siguiente reporte de caso, presentamos a una paciente pediátrica, asintomática, que se presentó a la consulta por detección de desaturación en oximetría de pulso. Las pruebas de laboratorio iniciales mostraron una anemia normocítica, normocrómica. Las muestras de gas venoso demostraron una p50 elevada. Después de extensas herramientas de diagnóstico, se diagnosticó una variante de Hb con baja afinidad al oxígeno, Hb Denver.
Subject(s)
Anemia , Hemoglobinopathies , Hemoglobins, Abnormal , Humans , Child , Female , Hemoglobins, Abnormal/genetics , Hemoglobins, Abnormal/analysis , Hemoglobins, Abnormal/chemistry , Oximetry , Hemoglobinopathies/diagnosis , Hemoglobinopathies/genetics , OxygenABSTRACT
Targeted therapies with MAPK inhibitors have proven to modulate the clinical manifestations of patients with Langerhans cell histiocytosis (LCH). We explored the presence of BRAFV600E mutation in our cohort of patients with LCH and cholestasis, sclerosing cholangitis, or liver fibrosis that presented resistance to chemotherapy. The BRAFV600E mutation was detected either in the diagnosis (skin and bone) or liver biopsy in our cohort of 13 patients. Thus, we observed a high incidence of BRAFV600E mutation in 100% either in diagnostic biopsy (skin and bone) or liver biopsy in patients with progressive liver disease, sequela, or liver transplant requirement.
Subject(s)
Cholangitis, Sclerosing , Cholestasis , Histiocytosis, Langerhans-Cell , Proto-Oncogene Proteins B-raf/genetics , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/epidemiology , Cholangitis, Sclerosing/genetics , Cholestasis/complications , Cholestasis/genetics , Histiocytosis, Langerhans-Cell/epidemiology , Histiocytosis, Langerhans-Cell/etiology , Histiocytosis, Langerhans-Cell/genetics , Humans , Liver Cirrhosis , Mutation , PrevalenceABSTRACT
La hidatidosis es una zoonosis producida por el parásito Echinococcus granulosus. En el ciclo zoonótico del parásito, el hombre es un huésped intermediario y sufre la enfermedad tras la ingesta de alimentos y agua contaminados por la materia fecal de animales infectados. En Argentina, la enfermedad constituye un problema importante de salud pública. Suele manifestarse con compromiso hepático y pulmonar. La afectación de otros órganos, que incluyen el corazón, es infrecuente.
Hydatidosis is a parasitic infection caused by the Echinococcus granulosus larvae, transmitted by the ingestion of infected food, characterized by the formation of cysts in vital organs. In Argentina, the disease is spread throughout the territory, constituting an important public health issue. The disease usually affects the liver and lungs. The affection of other organs is rare, and even more uncommon the affection of the heart. We present the case of a disseminated hydatidosis in a pediatric patient, whose initial clinical manifestation was an acute arterial embolism of the right limb caused by the rupture of a hydatidic cardiac cyst.
Subject(s)
Humans , Male , Adolescent , Echinococcosis/diagnosis , Embolism/etiology , Heart Diseases/diagnosis , Acute Disease , Echinococcosis/complications , Embolism/parasitology , Heart Diseases/complications , Heart Diseases/parasitologyABSTRACT
Hydatidosis is a parasitic infection caused by the Echinococcus granulosus larvae, transmitted by the ingestion of infected food, characterized by the formation of cysts in vital organs. In Argentina, the disease is spread throughout the territory, constituting an important public health issue. The disease usually affects the liver and lungs. The affection of other organs is rare, and even more uncommon the affection of the heart. We present the case of a disseminated hydatidosis in a pediatric patient, whose initial clinical manifestation was an acute arterial embolism of the right limb caused by the rupture of a hydatidic cardiac cyst.
La hidatidosis es una zoonosis producida por el parásito Echinococcus granulosus. En el ciclo zoonótico del parásito, el hombre es un huésped intermediario y sufre la enfermedad tras la ingesta de alimentos y agua contaminados por la materia fecal de animales infectados. En Argentina, la enfermedad constituye un problema importante de salud pública. Suele manifestarse con compromiso hepático y pulmonar. La afectación de otros órganos, que incluyen el corazón, es infrecuente. Se presenta un caso de embolia arterial aguda como manifestación clínica inicial de una hidatidosis diseminada en un paciente pediátrico, a partir de la ruptura de un quiste hidatídico cardíaco.
