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Glucose-6-phosphate (G6PD) deficiency is a common disease characterized by acute hemolysis induced by oxidative stress. More than 400 million subjects throughout the world carry the hereditary enzyme defect with the highest prevalences in Africa, Asia, and the Mediterranean region. In individuals affected by the erythrocytic enzymatic disorder, besides infectious diseases and diet, acute hemolytic crisis can be triggered by numerous drugs frequently used for the treatment of dermatoses. Taking into account the increasing number of immigrants from geographic regions with high prevalences of G6PD deficiency, dermatologists should be alert to the presence of disease.

Genetic defects of red cell membrane proteins constitute in Europe the most common cause of congenital hemolytic anemias. During the past decennium the defects and the pathogenetic mechanisms have been eludicated. Relatively simple hematologic tests allow for differentiation into groups with different severity of the disease. This allows prognostic assessment and careful risk-benefit evaluation for splenectomy.

Possible causes for a normocytic hyperregeneratory anemia are beside an incomplete treatment of iron deficiency, vitamin B12 deficiency or folic acid deficiency notably a hemolysis. After exclusion of other causes of hemolysis like immune hemolytic anemias, microangiopathic hemolytic anemias and hemoglobinopathies, an enzyme deficiency of erythrocytes should be considered. By far the most common form worldwide is the Glucose-6-phosphate deficiency. In the most frequent variants of this disease hemolysis occurs only during stress, imposed for example by infection, "oxidative" drugs or after ingestion of fava beans. The most serious clinical complication of the Glucose-6-phosphate deficiency is the rarely observed neonatal icterus. Some enzyme variants can cause chronic hemolysis which is described as chronic nonsperocytic hemolytic anemia. This form of chronic anemia can also be caused by other enzyme deficiencies, most frequently by the Pyruvate kinase deficiency. All other deficiencies of glycolytic enzymes are even rarer. It should be noted that in some of these very rare forms neurological rather than hematological symptoms predominate the clinical syndrome. If there is suspicion, on the basis of clinical symptoms and/or familial history, diagnosis of an enzyme deficiency can be achieved relatively easy by measurement of the enzyme activity. Accurate diagnosis might be helpful in therapeutic decisions (e.g. splenectomy in certain forms) and it is essential for genetic counseling, since certain deficiencies are transmitted as autosomal recessive disorders (e.g. pyruvate kinase deficiency), while the most common form, the glucose-6-phosphate dehydrogenase deficiency is linked to the X-chromosome.

This is the report of a female infant ten weeks of age, who was admitted to our hospital with hyperpyrexia, hemolytic anemia and disseminated intravascular coagulation. The further course of the disease was characterized by: continuing hemolysis resulting in severe normochromic, normocytic anemia, unrelenting disseminated intravascular coagulation, increasing hepato-splenomegaly with hyperbilirubinemia and ascites. No causative infectious organism could be identified. The infant died at the age of 14 weeks from respiratory insufficiency. Autopsy revealed massive hepato-splenomegaly, ascites and bilateral pneumonia. Histologic evaluation demonstrated lymphohistiocytic infiltrates of the periportal areas of the liver, the spleen and lymphnodes. Meninges were infiltered by macrophages with ingested erythrocytes. Differential diagnosis includes an infection with leptospira icterohemorrhagica (Weils disease) and erythrophagocytosis observed after various viral infections. Also histiocytosis X or malignant histiocytosis has to be taken into consideration. The most probable diagnosis in our patient is that of familiar hemophagocytic reticulosis although the familiarity in our patient was lacking. Intra vitam diagnosis can only be established by liver biopsy which could not be performed in our patient due to the severe coagulation disturbance.

Recently numerous defects of erythrocyte membrane proteins have been described in hereditary hemolytic anemias. An exact biochemical characterization of some different types of hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and the hemolytic anemias with increased cation permeability (hereditary stomatocytosis) is possible after analysis of membrane proteins with SDS-polyacrylamide gel electrophoresis, quantitative determination of spectrin, the relation of dimeric to tetrameric spectrin, and partial tryptic digestion of the spectrins. The known clinical heterogeneity of the mentioned disorders is now partially explained by the different biochemical defects of the erythrocyte membrane. In classical hereditary spherocytosis a close relationship between erythrocyte spectrin content and clinical severity has been found. The clinical manifestation in hereditary elliptocytosis and hereditary pyropoikilocytosis mainly depends on the functional disturbance of variant spectrins, especially their ability to form tetramers, i.e. their ability for self-association of the spectrin chains. In the hydrocytic form of stomatocytosis a deficiency of the integral protein band 7.2b has been documented. Besides the analysis of erythrocyte membrane proteins the classical methods used in the study of congenital hemolytic anemias cannot be missed. Signs of increased hemolysis, erythrocyte morphology, osmotic fragility, autohemolysis, heat and mechanical stability of the erythrocyte membrane, intracellular cation concentration and studies of other family members, are indispensable prerequisites for classification, prognosis, and indication of therapeutic efforts, especially splenectomy.

Glutathione reductase activity and phospholipid metabolism in red cell membranes were determined in a family with hereditary hemolytic anemia. A marked decrease of glutathione reductase activity and stability of reduced glutathione was found in combination with enhanced phospholipid-phosphate metabolism and decreased activity of the membrane-stabilizing enzyme lysolecithin-acyltransferase. In all cases splenectomy beneficially influenced the hemolytic process. Family studies revealed a dominant-autosomal genetic transmission.