[Congenital hemolytic anemias due to erythrocyte membrane and enzyme defects]. / Kongenitale hämolytische Anämien durch Membran- und Enzymdefekte der Erythrozyten.

Erythrocyte membrane and enzyme defects are the most common cause of congenital hemolytic anemias in the Central European population. Diagnostics include erythrocyte morphology, special biochemical tests such as osmotic fragility (AGLT) and EMA. For enzymopenic hemolytic anemias, cost-effective biochemical analysis remains the gold standard, supplemented by molecular genetic diagnostics when appropriate. Therapeutically, near complete splenectomy reduces hemolysis significantly for spherocytosis. The residual spleen at least provides a considerable phagocytic function and better response to immunisation and by inference possibly better protection against severe post-splenectomy infection. For pyruvate kinase deficiency, which is not so rare, a new molecular therapy (Mitapivat) is currently being introduced. In G6PD deficiency, there are very few drugs that cause hemolytic crisis. Sudden onset of hemoglobinuria is an early important hallmark of severe hemolytic crisis in G6PD deficiency and these patients should be hospitalized. Aplastic crises in the setting of parvovirus B19 infection occur in all congenital hemolytic anemias. Transfusion is not preventable in most cases. Iron-excreting treatment is required in the rare patients in need of chronic transfusion.

Inherited or acquired modifiers of iron status may dramatically affect the phenotype in dehydrated hereditary stomatocytosis.

Severe iron overload is frequent in dehydrated hereditary stomatocytosis (DHSt) despite well-compensated hemolysis and no or little transfusion requirement. We investigated 4 patients with proven DHSt, in whom the degree of hemolysis was closely related to iron status. Genetic modifiers increasing iron stores (HFE:pCys282Tyr, HAMP:c-153C>T mutations) were accompanied with high liver iron concentrations and increased hemolysis, whereas therapeutic phlebotomies alleviated the hemolytic phenotype. There were no manifestations of hemolysis in one patient with low iron stores. Hemolysis reappeared when iron supplementation was given. The search for genetic or acquired modifiers of iron status and the modulation of iron stores may help in the management of these patients.

Causes of hemolysis in neonates with extreme hyperbilirubinemia.

OBJECTIVE: We instituted a quality improvement process to enhance our capacity to diagnose genetic hemolytic conditions in neonates with extreme hyperbilirubinemia. STUDY DESIGN: During a 1-year period, whenever the total serum bilirubin (TSB) was >25 mg dl(-1) a special evaluation was performed. If we deemed an erythrocyte membrane defect likely, based on red blood cell morphology, EMA-flow cytometry was performed. Otherwise 'next-generation' sequencing was performed using a panel of genes involved in neonatal hyperbilirubinemia. RESULT: Ten neonates had a TSB ⩾ 25 mg dl(-1). Two others were evaluated as part of this process at the request of their attending neonatologists, because each had a TSB >14 mg dl(-1) in the first hours after birth and required phototherapy for ⩾ 1 week. Explanations for the jaundice were found in all 12 neonates. Five had hereditary spherocytosis, three of which also had ABO hemolytic disease. Two had pyruvate kinase deficiency. One had severe G6PD deficiency. The other four had ABO hemolytic disease. CONCLUSION: On the basis of the present small case series, we suggest that among neonates with extreme hyperbilirubinemia, it can be productive to pursue a genetic basis for hemolytic disease.

Sobrecarga de ferro em adolescente com xerocitose: a importância da ressonância nuclear magnética / Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging

Relatar um caso de sobrecarga de ferro secundária à xerocitose, uma doença rara, em uma adolescente, diagnosticada por meio de ressonância magnética em T2*. Relatamos o caso de uma paciente sintomática com xerocitose, nível de ferritina de 350ng/mL e sobrecarga de ferro cardíaca significativa. Ela foi diagnosticada por ressonância magnética em T2* e recebeu terapia de quelação. Análise por ectacitometria confirmou o diagnóstico de xerocitose hereditária. Na sequência, a ressonância magnética em T2* demonstrou resolução completa da sobrecarga de ferro em vários órgãos e novo ecocardiograma revelou resolução completa das alterações cardíacas anteriores. A paciente permanece em terapia de quelação. Xerocitose é uma desordem genética autossômica dominante rara, caracterizada por estomatocitose desidratada. O paciente pode apresentar fadiga intensa e sobrecarga de ferro. Sugerimos o uso regular de ressonância magnética em T2* para o diagnóstico e controle da resposta à quelação de ferro em xerocitose e acreditamos que o exame pode ser útil também em outras anemias hemolíticas que necessitam de transfusões.

To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging.

To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

Hidrops fetal no inmune asociado a talasemia familiar: transfusión intravascular / Non-immune fetal hidrops associated to familiar thalasemia: intravascular transfussion

Se presenta un caso de hidrops fetal no inmune provocado por una anemia hemolítica severa secundaria a una talasemia familiar pesquisada a las 28 semanas y que revierte luego de transfusión intravascular, TIV, practicada en nuestro servicio. Se analiza el diagnóstico, manejo prenatal y posterior evolución

Detection of pyrimidine 5'-nucleotidase deficiency using 1H- or 31P-nuclear magnetic resonance.

We describe here a further Japanese family with pyrimidine 5'-nucleotidase (P5'N) deficiency diagnosed using a nuclear magnetic resonance (NMR) spectrum, in Kumamoto prefecture where two families having the disease have been reported before. The specific spectra in 1H-NMR of P5'N deficient erythrocytes were due to three methyl protons of CDP-choline at 3.22 ppm and to H-2, H-8 and ribose-1' of pyrimidine nucleotide phosphate(s) in the lower fields (at 5.82 and 8.00 ppm). The other specificities in 31P-NMR spectra were due to CDP-choline, CDP-ethanolamine and UDP-glucose. Those spectra were not detected in other types of hemolytic anemia.

Infantile pyknocytosis: a cause of intrauterine haemolysis in 2 siblings.

Infantile pyknocytosis, a rare cause of intrauterine haemolysis and potential perinatal death, is described and the relevant literature reviewed. Treatment consists of preterm delivery with exchange transfusion as necessary to control the haemolytic process and hyperbilirubinaemia.