Martha Kreimer-Birnbaum

Hereditary microcytic anaemia in the mouse; studies in iron distribution and metabolism

Summary. Iron distribution and metabolism have been studied in hereditary iiiicrocytic anaemia of tlie mouse (gene symbol mk), an autosonial recessive trait cliaractcrizcd by hypoclironiia and microcytosis. Evidence of iron deficiency was hutid in the forin of depleted body stores, hyposidcraemia, an increased total iron biiiding capacity of tlic plasma and a high free erythrocyte‐protoporyhyrin level. I lowcvcr, the failure to find citlicr rapid clearance and high utilization of tracer doses of 59Fe or a complete response to pareliteral iron treatment indicated that simple iron deficiency was not the cause of tlie anaemia. It is suggested that generalized impairmcn t in tlie cellular uptake of iron involvingthe transfer of iron from the intestinal lumen to tlic mucosa and from tlie plasma to the erythroblast may provide a unitary explaiiation of licreditary microcytic anaemia.

Pyrrole pigments in normal and congenitally anaemic mice (+/+, W/Wv, ha/ha, nb/nb, mk/mk, f/f and sla/Y)

Abstract 1. Values for faecal urobilinogen (UBG), serum bilirubin, and free erythrocyte protoporphyrin (FEP) are reported for normal and anaemic mice with six different hereditary anaemias. 2. Greatly increased faecal UBG and elevated serum bilirubin were found in mice with severe haemolytic anaemia (nb/nbandha/ha). 3. Mice with microcytosis (mk/mk) and sex-linked anaemia (sla/Y), both showed increased FEP and only moderate increase of faecal UBG. 4. Values for W/Wv mice fell within the normal ranges. 5. FEP levels in normal 15-day foetal red cells were extremely high. Levels for 15-day flexed anaemic foetuses (f/f) were lower, but markedly aboved adult level.

Interrelationship of Pyrrole and Globin Metabolism in β‐Thalassaemia *

Detailed metabolic studies in a case of β‐thalassaemia intermedia following 14C‐2‐glycine administration demonstrate some of the interrelationships of pyrrole pigments and haemoglobins, and some secondary effects of a β‐thalassaemia mutation.

Uroporphyrinogen synthase in human blood: Developmental studies

Abstract Uroporphyrinogen synthase (URO-S), the enzyme that catalyzes the conversion of porphobilinogen to uroporphyrinogen I, has been measured in whole blood lysates by a fluorometric microassay. Cord and fetal bloods have 3 and 6 times the specific activity, respectively, of adult control subjects. The three groups seem to present a similar genetic heterogenity with ratios of highest to lowest URO-S specific activity close to 2. These results establish normal ranges for URO-S activity in human blood, which may be useful for the early detection of carriers of a gene for acute intermittent porphyria.

Heme and Globin Synthesis Control: Observations in vivo in Beta Thalassemia

After administration of glycine-2-14C to a patient with thalassemia, the specific activities of heme and globin of F hemoglobin were consistently higher than those of hemoglobin A. After reaching a maximum, the ratio of the specific activity of heme to that of globin remained constant within each hemoglobin. Explanations considered include dilution by preformed subunits, differential turnover of hemoglobins, and possibly more than one heme-synthesizing pool.

Afro-Americans and acute intermittent porphyria (AIP)

Abstract AIP in blacks has been reported in sporadic cases from the African and North American continents, but no detailed family evaluations are available. We report here clinical, biochemical and genetic studies on two Afro-American families, each spanning three generations.

Acute porphyrias: Differential diagnosis and family studies

Abstract 1. 1. Studies on the differential diagnosis of the acute porphyrias are presented. 2. 2. Five families carrying Acute Intermittent Porphyria (AIP) are summarized. 3. 3. Early detection of asymptomatic carriers of AIP has been achieved with the uroporphyrinogen-I-synthase (URO-S) assay. 4. 4. A family with Variegate Porphyria (VP) is presented. 5. 5. A family with Coproporphyria (CP) is described. 6. 6. In the two tatter families, asymptomatic carriers have been detected by analysis of fecal porphyrins.

Haemoglobin metabolism in mice with a hereditary iron deficiency anaemia (sla/Y)

1. 1. Haemoglobin was labelled in vivo in normal mice and in mice with iron deficiency anaemia due to the X-linked gene mutation, sla. 2. 2. Two main red cell populations are found in normal mice, one subject to accelerated destruction and the second with a longer finite life span. 3. 3. In iron deficient sla / Y mice, haem and globin labelling indicate random haemolysis and shortened red cell survival. 4. 4. Specific activity curves of faecal urobilinogen show complex “early” labelling patterns. They confirm mean red cell survival in both normal and anaemic mice. and indicate increased ineffective erythropoiesis in the sla/Y animals with iron deficiency.