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Idiopathic Steatorrhea Presenting with Different Manifestations in Sisters C

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Idiopathic Steatorrhea Presenting with Different Manifestations in Sisters C FEBRUARY 1, 1964 * VOL. 90, NO. 5 Idiopathic Steatorrhea Presenting with Different Manifestations in Sisters C. R. RALLY, M.D., D. S. MUNROE, M.D. and A. BOGOCH, M.D., Vancouver, B.C. IDIOPATHIC steatorrhea (non-tropical sprue) is a complex metabolic disorder characterized by multiple defects of intestinal absorption. There ABSTRACT is considerable evidence to indicate the importance Although it is well known that the incidence of inheritance in the etiology of this disease. The of idiopathic steatorrhea is much higher in incidence of celiac disease and idiopathic steator- relatives of patients with this disease than rhea is much higher in near relatives than it is in it is in the general population, there has the general population.'-3 Ebbs4 commented on the been little comment on the variability of occurrence of celiac disease in twins and stated symptoms in familial cases. Two sisters with this disease are reported. One presented that all members of five sets of identical twins with a relatively acute history of diarrhea, were affected, whereas in six sets of non-identical weight loss, fatigue and peripheral edema twins only three sets showed disease in both twins. and was found to have a normal hemo- Thompson5 published a list of reported cases of globin, hypocalcemia and a markedly de- celiac disease with more than one member in a creased prothrombin activity. Her elder family and found a history of celiac disease in sister tended to constipation and had a 10- 13% of the siblings, 6% of their parents and 1% year history of refractory iron-deficiency of their grandparents. Similar conclusions were anemia. The diagnosis was confirmed in obtained in two other studies of the genetics of both by peroral jejunal biopsy. celiac disease.6' 7 In the most recent of these Carter, Sheldon and Walker' found the risk in the general population to be about 1 in 3000, whereas the incidence in parents and siblings was approxi- mately 1 in 40. Present evidence supports the con- cept that idiopathic steatorrhea is attributable to a specific inherited metabolic defect which results in a deficiency of certain intestinal mucosal proteo- lytic enzymes required for the hydrolysis of the glutamine-containing peptides of gliadin. Although the diagnosis is relatively simple if the disease presents with a classical history of diar- rhea, it is important to remember that intestinal symptoms may be minimal or absent, and that pa- tients may present with varied manifestations in- cluding hypocalcemic tetany, bone pain due to osteomalacia, megaloblastic or iron-deficiency anemia, or hemorrhage from prothrombin de- ficiency. There has been little comment in previous re- ports on the variability of the symptoms in familial From the Department of Medicine. Vancouver General Hos- pital and the University of British columbia. Vancouver. 346 RALLY AND OTHERS: IDIOPATHIC STEATORRH.EA TABLE I. Normal values Case 1 Case . Hemoglobin.14.5 g. = 100% 14.8 g. 9.3 g. Red blood cell morphology Occasional +1 macrocytes macrocytes +2 microcytes Moderate hypochromia R.B.C.4.2 - 5.4 million/c.mm. 4 million Hematocrit.42 i 5% 34% M.C.H.C.33 . 3% 27% Serum iron.80-180 pg. % 60 pg.% 54 pg.% Stool-occult blood.Negative Negative . Negative x 9 Serum albumin.4-6 g./100 ml. 2.4g. 4.7g. Serum globulin.1.5-3 g./100 ml. 1.9 g. 2.3 g. Prothrombin activity.100% 12% 100% Serum calcium.9-11 mg.% 7.4 mg.% 9.2 mg.% Serum phosphate.2-5 mg./100 ml. 5.5 mg.% 3mg.% Oral glucose tolerance, 100 g. glucose.Fasting 80-120 mg.% Fasting-86 mg.% Rise to a peak averaging 1/2 hour-82 mg.% 50% above fasting 1 hour-55 mg.% within 60 mm. 1½ hours-72 mg.% Fall to fasting level 2 hours-61 mg.% within two hours Blood sugar-i hour p.c.Average of 40 mg. 83 mg.% above fasting Xylose tolerance, 25 g. orally.Over 25% excreted in 6.8% 9.3% urine in five hours Fat balance study, 70g. fat each day for three days -% of ingested fat absorbed. 95% 76% 67% and no organs or masses were palpable. There was a uniform moderate increase in the diameter of the slight pitting edema of the legs, six ecchymoses up to small bowel with flocculation and segmentation. A one inch in diameter over the thighs, and one, three barium enema examination was negative. Jejunal biopsy inches in diameter, over the right mid-buttock. The showed well-marked changes characteristic of idiopathic remainder of the examination revealed no abnormal steatorrhea (Fig. 1). The laboratory findings are re- findings. Sigmoidoscopy to 25 cm. revealed no ab- corded in Table I. normalities except for slight hyperemia of the mucosa, and a biopsy of the sigmoid colon 20 cm. from CAsE 2.-Mrs. A.M., a 38-year-old sister of Case 1, the anus was normal. A barium meal study revealed was admitted to the Vancouver General Hospital in September 1962 for investigation of a refractory hypo- chromic anemia. This anemia had been severe for at least 10 years and previous investigation had failed to determine its cause. She had received multiple blood transfusions, with considerable temporary improvement in her symptomatology. The administration of folic acid and vitamin B12 had been ineffectual, and she stated that she was unable to take oral or parenteral iron because of nausea, vomiting, hives and pruritus. In 1954 she complained of upper abdominal pain and was re- ferred to a psychiatrist, who concluded that she had a severe psychoneurosis with a doubtful prognosis. In November 1960 her hemoglobin was 44% and a sternal marrow test was normal except for hypochromic red cells. Throughout 1961 the hemoglobin remained below 52%. The chief presenting complaints in September 1962 were weakness and fatigue. Her appetite was very good. Slight dysphagia and frequent heartburn had been present for many years but there was no abdominal pain or distress. Slight constipation was the rule. She Canad. Med. Ass. J. Feb. 1, 1964, vol. 90 RALLY AND OTHERS: IDIOPATHIC STEATORRHEA 347 took laxatives about twice a week and had about four following rigidly a gluten-free diet, and delay in bowel movements a week. The stools were usually recovery for periods of up to two years8 may test normal in colour although rarely were light. On one this faith and lead to doubt of the initial diagnosis occasion only, in March 1962, she had an acute, brief and to premature abandonment of a correct dietary episode of severe diarrhea. For several years, she had had irregular menstrual periods at three- to four-week regimen. Peroral jejunal biopsy is the definitive intervals; each lasted for three days, with a heavy procedure to establish the diagnosis. flow for only one day. There was no apparent blood The histological changes in the jejunum are loss from any other site. characteristic but not specffic for non-tropical sprue Her father had died of "kidney trouble" at age 65; and celiac disease. There may, however, be no her mother, at age 46 of unknown cause. Four brothers correlation between the severity of the anatomical are alive and well. Her sister's history is reported in lesion and the degree of malabsorption, as assessed Case 1. biochemically. Reduction in the epithelial surface She was a thin, pale, tense woman with questionable is the most dependable single histological criterion. clubbing of the fingers. The blood pressure was Changes in the villi vary from mild blunting and 110/70 mm. Hg. Physical examination revealed no widening to complete disappearance. The crypts other abnormalities. are elongated. The lamina propria is infiltrated to The results of laboratory studies are recorded in a varying degree with plasma cells, lymphocytes Table I. and eosinophils. The lining columnar epithelial cells are flattened, and their nudei fail to maintain a regular basal orientation and are irregular and abnormally dense. Mitoses are not confined to the crypts but may extend to the surface cells. As seen by electron microscopy, the microvili of the epithelial columnar absorbing cells are short, irregular, and less numerous than normal. In chil- dren, especially those with a brief history, complete histological recovery may take place. In some adults on a strict diet marked improvement in the proximal jejunum or reversal to normal may occur.9 Despite the numerous case reports of idiopathic steatorrhea in siblings, there has been little com- ment on the variability of expression of the disease in these siblings. Familial cases have usually been discovered because of the similarity of their symp- toms; for this reason the vast majority have diarrhea. Although the two sisters reported here resided in the same small town, their symptoms were so dissimilar that no connection was initially suspected. The manifestations of idiopathic steator- rhea include diarrhea, weight loss, weakness, glossitis, stomatitis, flatulence, crampy abdominal distress, anemia, hypoproteinemia, edema, club- bing, osteomalacia, tetany and hypotension. Mild constipation was the rule in the second patient and because of this steatorrhea had never previously been considered as a possible cause of the iron deficiency anemia. Sprue without diarrhea has been reported by many authors. This occurred in 11 of 163 patients reported by Badenoch,'2 in 12 of 124 patients at the Mayo Clinic,'3 and in 20 of 100 patients reported by Cooke, Peeney and Hawkins.3 Four of 94 patients of Bossak and co- workers1' had always had normal bowel move- ments and one complained of constipation. Although hypochromic anemia is common in celiac disease, the characteristic erythropoietic dis- turbance in adult non-tropical sprue is the develop- ment of macrocytosis. There may be macrocytosis without anemia in cases of mild disturbance, and macrocytic or megaloblastic anemia in more severe cases.
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