A Case of Atransferrinemia and 35 Cases of ypotransferrinemia as Detected by Radioassay of H Total Iron-binding Capacity of the Serum iroshiSaito, MD, Yoshiaki Kato, MD, Takashi Suzuki, MD, and Hajime Kato, MD Department of Radiology, and Department of Internal Medicine, Nagoya University School of Medicine, Nagoya Total iron-binding capacity (TIBC) of the serum was determined in 600 patients by the radioassay method devised by Saito. Fifty-four fig/dl of TIBC, which is as low as that of previouslyH reported cases of congenital atransferrinemia, was found in a patient with marked hypoproteinemia probably due to protein losing enteropathy as shown by a high plasma RISA disappearance rate of 41 percent per day. The patient was diagnosed as having secondary atransferrinemia on the bases of hematological findings, iron metabolism and other tests. Thirty-five of 600 patients whose serum TIBC levels were determined by radio- assay had low TIBC level below 200 [tg/dl. Twenty-one of the 35 (60%) had blood diseases, 13 (37%) had malignancies and 7 (20%) had diseases of digestive organs. TIBC was markedly increased in iron deficiency anemia, while it was normal or decreased in other diseases. IBC radioassay is a simple, highly accurate and efficient method of measuring transferrin. T Key Words: Transferrin, Serum iron, Unsaturated iron-binding capcity of serum (UIBC), Protein losing enteropathy (PLE), Hypoproteinemia, Plasma RISA clear- ance, Radioiron utilization, Storage iron deposition, Mechanism of iron absorption, In vitro saturation assay. Five cases of congenital atransferrinemia is nowcommercially available. Recently the have been reported so far. Besides, there authors performed determination of serum are 4 reports on secondary atransferrinemia TIBC on 600 patients using the TIBG kits and suspected atransferrinemia. and found 35 patients with TIBC levels To make diagnosis of atransferrinemia, below 200 ftg/dl, one of them had extremely immunoassay of transferrin (Tf) or measure- lowserum Tf level. ment of both serum iron (SI) and un- saturated iron-binding capacity (UIBC) is MATERIALS AND METHODS essential. Oneof the authors, Saito, devised TIBG and UIBC were measured by the method of TIBG radioassay10"125, and using Res-O-mat TIBC and UIBC kits es-O-mat TIBG kit based on the method produced by Dai-ichi Radioisotope Labora- tory, Ltd., Japan. The amount of Tf in R Received for publication March 2, 1977. Reprint requests to : Hiroshi Saito, Department mg/dl was obtained by dividing TIBC of Radiology, Nagoya University School of value in [tg/dl by 1.3. At the same timeTf Medicine, 65, Tsurumai-cho, Showa-ku, Na- was determined by using Behringwerke's goya, 466, Japan. Immunodiffusion Platten. 342 JapJ Med Vol 16, No 4 (Oct 1977) Atransferrinemia by TIBG-radioassay TIBG was determined on 600 different on legs. Laboratory data were listed in sera which had been sent to the Radio- Table 1. Marked hypoproteinemia with isotope Laboratory of Nagoya University hypalbuminemia, increased a2-globulin level, Hospital for the determination of UIBC. hypocalcemia, hyperlipemia and severe Plasmas or sera obtained from healthy stu- hypotransferrinemia were the outstanding dents of Nagoya University School of Medi- features. High T3RU and somewhat low cine were used as normal controls. thyroxin level were noted, indicating de- letion of thyroxin binding protein. Case Report p Course in the Hospital: Despite severe M.N., 24-year-old Japanese girl, was ad- hypoproteinemia, edema was successfully mitted to Nagoya University Hospital with treated with 40-80mg of furosemide daily, suspected protein losing enteropathy on but recurred soon after the drug was with- September 9, 1974. drawn. On September 30, she had a brief Family history was not contributory. episode of shock followed by marked tachy- Past history was unremarkable except for cardia and tachypnea lasting for several passing 2 to 3 loose stools daily since she days. In December, she developed leg was a pupil of an elementary school. edema,ascites, fever and cough of several In July of 1970, she developed edema on days' duration. upper and lower limbs, general fatigue and Plasma protein level remained low and fever of about 39°C of 4 days' duration. rarely rose above 4g/dl. Striking hyper- Proteinuria and decreased plasma protein catabloic hypoproteinemia, as shown by a level were also noted. The edema dis- rapid RISA disappearance (Figure 1), appeared after diuretic therapy. She was strongly suggested the existence of protein admitted to Kariya Toyota Hospital with losing enteropathy (PLE), for urinary pro- a diagnosis of nephrotic syndrome on July 20, 1970 and was discharged in May of1971, since physical and laboratory findings were 100% normalized. In July of 1973, edema and hypoproteinemia reccurred. She was treated Normal rate: less than 5%/day as inpatient at Anjo Kosei Hospital from August 22 to 27 inclusive. In May of 1974, she developed edema which increased steadily thereafter. In July, she was ad- mitted to Anjo Kosei Hospital with gene- Patient's rate: 41 %/day ralized edema, cough, pleural effusion, marked hypoproteinemia and elevated ESR. By kidney biopsy performed on July 31, a < pathologic diagnosis of membranous glo- CO merulonephritis was made, while urinary 3 protein was negative. Then she was moved to Nagoya University Hospital for further study. Physical findings at admission: The patient was rather small but normally de- veloped girl. Height was 148cm and body weight 44kg. BT 36°9/C. Pulse was 88 per minute and was regular. BP was 108/64 mmHg. Her conjunctiva appeared anemic 5 6 7 8 10 and striae cutis distensae were noted on Days abdominal wall. There was a mild edema Fig. 1. Plasma RISA disappearance curve. Jap J Med Vol 16, No 4 (Oct 1977) 343 Saito et al Table 1. Laboratory data. 1974 1975 Sept Oct Feb Apr Total protein (6.8-8.2)g/dl 3.6 3. 3.7 4.1 5.5 Albumin % 24.8 28. 22.5 25.3 38.7 <*-l globulin 6.7 5.0 5.4 6.1 6.5 <x-2 44.9 43.4 35.1 38.4 21.5 10.1 10.8 13.1 10.8 P- 23.3 13.5 26.2 17.1 22.5 GOT (15-36JU 64 48 29 26 24 GPT ( 9-31)U 32 33 18 18 18 Cholesterol (116-228)mg/dl 349 348 236 314 178 Alkaline phosphatase (3.2-10.5) 55.8 6.4 4.3 5.2 5.6 LDH (130-286) 370 130 160 120 0 Cholinesterase (0.76-1.30) PK 0.52 45 0.8: Bilirubin, total (0.17-0.98)mg/dl 0.3 0.2 0.3 0.3 direct (0 -0.2 ) 0.2 0.1 0.1 0.2 0.2 TTT (0-4)U 5 2 3 BUN (8.0-18.5)mg/dl 7.2 9.8 ll.5 ll.1 Na (135-144) mEq/1 137 133 136 132 K (3.2-4.9) 4.5 4.9 5.1 4.6 Cl ( 95-185) 109 105 103 100 Ca (4.2-4.9) 4.0 3.1 3.8 4.0 Amylase (40-135) Caraway unit 60 46 51 WBC fi /cmm ,000 ,300 10,000 ,900 RBC 10 /cmm 77 4.52 3 64 4.13 4.13 Hb g/dl 10.8 13.5 10.5 12.5 ll.2 r% Eematocrit 34 40. 31.0 35.4 34.2 Platelets 10^/cmm 2.9 2. 2.85 Reticulocytes % 0. ESR 1 hour mm 125 124 108 106 2 136 140 116 118 Triglyceride ( 43-168)mg/dl 1,558 ,542 1.780 446 /3-lipoprotein (380-800) 1,100 862 840 365 Phospholipid (155-270) 493 381 413 217 FFA (0.2-0.6)mEq/l 0.65 0.19 0.15 TIBC ( 356±39)jjg/dl 54 81 77 UIBC ( 251±49) 25 51 42 SI ( 105±25) 29 .7 30 35 Prothrombin time (control 12.0) 10.6 Thrombo test (70-130)%/ll.7sec over 100 26.7 seconds Fibrinogen (200-400)mg/dl 688 D-xylose excretion test (4 -8)g 6.0 Glucose tolerance test normal curve T, resin uptake (25-35)% 38.1 THyroxin ( 5-14)jug/dl 4.6 RISA half time (14 < )days 1.7 fractional catabolic rate 41 131-I-trio.lein absorption blood counting (13<)% 30.8 stool ( 2>) 1.3 Schilling test 24hr urine (8.0<)% 16.6 Fe absorption (with 4rag of carrier in the form of FeSO4 (Japanese female by whole body counting) 33%, when retics = 0.3% 28±8%) Desferal test (lOOOmg desferrioxamine i.m. injection) 1.2mg Fe/day (1<) Ferrokinetics PID Tl/2 = 27min (60-120) PIT = 0.49mg/kg/day (0.4-0.9) %RCU = 91% (85-100) RCV = 724ml PV = 1550ml BV = 2274ml Erythroid marrow distribution : Larger over the abdomen and chest than pelvic region at 5 and 24 hours Radioiron deposition in the liver by transverse linear scan : Increased at 5, 24 and 10 days Radioiron deposition in the spleen by transverse linear scan : Increased slighthy at 10 days Intestinal blood loss by stool counting : 0.2-l.lml/day (normal) (reabsorption is neglected) Mean red cell life span with 59-Fe = 51days tein was negative on repeated urinalysis. was often positive, blood loss in the gut However, UGI, BaE and X-ray examination determined with radioiron was 0.2 to 1.1 ml of the small intestine by means of duodenal per day, i.e., within normal range. RBC and intubation revealed no abnormalities in hemoglobin level were generally within gastrointestinal tract. Jejunal biopsy and normal limit. Ferrokinetics were performed absorption studies did not yield any posi- and the results are shown in Table 1, and tive results.