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Summary A new syndrome of congenital hypoplastic anemia and triphalangeal thumbs has been found in two brothers, at least one of whom also has a congenital heart defect. It is not possible from the present data to discriminate between X-linked and autosomal recessive modes of inheritance. This condition is clearly distinguishable from Fanconi's fancytopenia, the radial aplasia-thrombocytopenia, and the Holt-Oram syndromes by physical and hematologic criteria.

Summary A case of congenital hypoplastic anemia is presented. The outstandingfeatures were a severe diminution in the erythropoietic and granulocytic bone marrow elements with a less marked decrease in thrombocytes. There were no evidences of blood regeneration or of destruction. Life was maintained only by repeated transfusions, and none of the blood-producing substances were of any value. The infant seemed able to adjust himself perfectly to low hemoglobin and red cell levels. In spite of rather low platelet counts there was no hemorrhagic tendency. At the age of 21 months the count suddenly began to rise and at this writing is practically normal. No etiologic factor was discovered. An interesting sidelight is the remarkable resistance to infection and recuperative power of this infant, even during periods of profound anemia.

Hereditary ectodermal dysplasia presents a syndrome of incomplete development of the epidermis and its appendages and is associated with sweating disturbances, anomalous growth of the nails and teeth, and hypotrichosis. The clinical picture may vary considerably, depending on the degree of development of each of these signs. It has been pointed out that the disease involves not only skin and structures derived from ectoderm, but also organs of mesodermal and endodermal origin.*We have recently studied a case of ectodermal dysplasia which was associated with severe refractory anemia of long duration. As this case affords interesting observations on the problem of hereditary ectodermal dysplasia, as well as primary refractory anemia, a detailed description of the case will be presented. Report of a Case The patient was hospitalized on Dec. 26, 1953, because of abdominal pain, weakness, and fatigability. From his youth he had

F OLLOWING close upon Landsteiner and Wiener ' s I discovery of the Rh factor, Levine and his associates 2 developed the idea of maternal isoimmunization i n the pathogenesis of erythrob]astosis fetalis, demonstrating the relationship between Rh incompatibili ty and erythroblastosis fetalis. In over 90 per cent of the cases the fa ther and child were Rh positive and the mother, Rh negative. Clinically, erythroblastosis fetalis is considered as a single disease with three chief recognized forms, called fetal hydrops, icterus gravis, and congenital anemia. Erythroblastosis fetalis is generally considered as being synonymous with Rh incompatibili ty and associated with Rh-negative mothers in over 90 per cent of the eases. However, not ~11 cases of erythroblastosis fetalis are caused by the Rh antigen-antibody reaction. On a theoretical basis, incompatibilities can occur f rom any blood antigen which is present in the father, t ransmit ted to the offspring, and absent in the mother. The Rh subgroups, the H r factor, and ABO group incompatibilities are possible etiological agents. The M, N, and P factors are apparent ly not antigenic. Tovey a gives four reasons why the fetus enjoys protection from the mother 's agglutinins in heterospeeific pregnancies

In 1967, Wendt and Heimpel 1 described a new form of macrocytic anemia in a pair of dizygotic twins. The anemia, detected in early childhood, was associated with ineffective erythropoiesis and with characteristic erythroblast morphologic features. These included multiple nuclear anomalies, megaloblastoid change, and internuclear chromatin bridges. The disease was named congenital dyserythropoietic anemia (CDA). The same authors 2 subsequently classified the disorder as CDA type I to distinguish it from a morphologically different form of congenital anemia due to ineffective erythropoiesis (CDA type II), reported independently by Crookston et al, 3 and from a third type of hereditary dyserythropoietic anemia, which had been described earlier by Wolff and von Hofe as "familial erythroid multinuclearity" 4 and by Bergstrom and Jacobsson as "hereditary benign erythroreticulosis" 5 (CDA type III). CDA type II is being observed with increasing frequency, 6-9 but only nine patients with CDA type I have been reported

A 12 year old Caucasian girl with congenital anemia and episodic jaundice was studied. Hemolysis was not present as evidenced by a normal Cr51 red cell survival time. Congenital dyserythropoietic anemia type II (Heimpel) was diagnosed after finding a positive acidified serum test of the circulating red cells and marked erythroid hyperplasia with erythroblastic multinuclearity in a bone marrow aspirate. A bone marrow specimen was labeled with H3T in vitro and autoradiographs prepared. Electron microscopy was also done on the same specimen. The percent of uninucleated normoblasts labeling with H3T indicated normal DNA synthesis. However, only 2% of the binucleated and none of the multinucleated polychromatophilic normoblasts labeled with H3T, indicating decreased DNA synthesis in these forms. By electron microscopy, excessive membrane structures forming invaginations or cisternae and encompassing the circumference of the cell in varying degrees were seen in the majority of the normoblasts. The nuclear membrane appeared normal. Despite the abnormality, nuclear extrusion was noted in these cells. Small cisternae were also found at the periphery of the cell in about 1–2% of the mature erythrocytes. These findings are suggestive that the cells with more severe structural abnormalities and/or decreased DNA synthesis are destroyed intramedullary and the circulating red cells are derived from a less abnormal portion of precursors.

The normal new-born infant has a high erythrocyte count with a correspondingly high content of hemoglobin. In the past ten years, there has appeared in the pediatric literature a small group of case reports of so-called primary anemia of the new-born. No satisfactory explanation of the pathogenesis has been offered. Such cases have been reported by Ecklin, 1 Donnally, 2 Susstrunk, 3 Sanford 4 (three cases), Sidbury, 5 Canino, 6 Bonar, 7 Ehrmann, 8 Happ, 9 Gelston and Sappington, 10 and Greenthal. 11 In addition, Grulee12 mentioned having seen three or four cases; Foote 13 had five cases, and McClelland 14 had one case. In a recent monograph, Blackfan, Baty and Diamond 15 briefly described a case and stated that they have the records of four cases as yet unpublished. In all, the occurrence of a total of twenty-eight cases has been reported in the literature. We are in accord with

The subject of anemia of the new-born has recently taken on a new interest. Finkelstein 1 (in 1911) and Lichtenstein 2 (1917) first drew attention to the possible occurrence of anemia in the new-born. Ecklin 3 (1919), however, was the first to report "a case of severe anemia in the new-born." Following this, cases have appeared under the titles of idiopathic, primary, essential and congenital anemia. Pritchard and Smith 4 (1931), in a careful survey of the literature, tabulated fifteen cases and mentioned fourteen additional cases observed though not described by Grulee, Foote, McClelland and Blackfan et al. Abt 5 (1932) analyzed the reported cases and presented a case of his own which also showed a mononuclear erythrophagocytosis in the circulating blood. Diamond, Blackfan and Baty 6 (1932) added six cases and concluded that universal edema of the fetus, icterus gravis neonatorum and anemia of the new-born are closely related

In recent years there has come to be recognized a group of cases of severe primary anemia of the new-born. Attention was first drawn to this disease in 1919 by Ecklin,1who described a case of severe primary anemia in a 12 day old infant who recovered seven months later. By 1931 Abt2was able to collect reports of fifteen cases, which he completely reviewed, and Blackfan and his associates3have reviewed a few cases reported since. So far as we are able to determine, thirty-nine cases have been described in the literature. The condition has been designated as "anemia of the new-born" or "congenital anemia."4The cases of this type of anemia have been separated from a large group of cases of anemia to conform with Ecklin's original description. The signs and symptoms have been thoroughly reviewed by Abt,2Blackfan,5Pasachoff and Wilson

In 1912, Rautmann 1 first applied the term Erythroblastose to a condition in a hydropic fetus in which there was evidence of excess hemopoiesis in the liver, spleen and kidney. Since that time the term has been used to designate a group of conditions including fetal hydrops, fatal jaundice of the newborn and congenital anemia. Since the discovery of the Rh factor by Landsteiner and Wiener 2 and the application of the knowledge gained through this discovery to the problem of erythroblastosis by Levine and his associates, 3 the term has been employed to designate the condition arising through incompatibility of blood factors between mother and fetus. Confusion now exists in the literature as to what constitutes erythroblastosis. There are those who state that hemolysis is the distinguishing feature of the condition; others state that the essential criterion is the presence in the fetus, at or near term, of extramedullary

Within the past few years a triad of apparently closely associated disorders affecting the hematopoietic system of the fetus and the new-born infant has received considerable recognition in the pediatric literature. This group consists of universal edema of the fetus, familial icterus gravis neonatorum and congenital anemia of the new-born. Attention was early called to the relationship existing between universal edema of the fetus and icterus gravis neonatorum by the frequent familial incidence and the similarity of the pathologic pictures. However, congenital anemia of the new-born is a rather newly defined clinical entity, and its association with universal edema of the fetus and icterus gravis neonatorum has therefore only recently been appreciated. Universal edema of the fetus 1 (congenital fetal hydrops) is a relatively rare condition that has been known for several centuries. The most striking feature of the disease is generalized edema. The liver and spleen are greatly enlarged.