William K. Schubert

Deficient Activity of Hepatic Acid Lipase in Cholesterol Ester Storage Disease

Absence of lysosomal acid lipase activity in the liver is described in cholesterol ester storage disease and Wolmans disease. This enzyme deficiency may result in the excess hepatic cholesterol ester found in both conditions. However, clinical, genetic, and histopathologic differences suggest that the two conditions are separate diseases not completely explained by deficient enzyme activity.

Antibody deficiency syndrome associated with beta-2 macroglobulinemia.

A patient with an uncommon variation of the antibody deficiency syndrome was studied by means of quantitation of serum immunoglobin response to injected antigens, determination of granulocyte kinetics, and skin homografting. The immunoglobin defect was defined as a persistent absence of beta-2A globulin, severe to moderate hypogammaglobulinemia, and extreme beta-2 macroglobulinemia (concentrations of 400 per cent of the normal mean). The response to injected antigens indicated that the patients mechanism for the synthesis of macroglobulin was intact and appeared to compensate partially for failure to synthesize nonmacroglobulin antibody. A skin homograft underwent a delayed rejection. Survival studies of granulocytes showed a decreased survival time for normal white cells infused into the patient. At the age of 27 months the patient died of alveolar proteinosis and Pneumocytis carinii pneumonia. The thymus was noted to be atrophied, and a peculiar deformed type of Hassalls corpuscle was found.

Benign recurrent intrahepatic cholestasis, with response to cholestyramine☆

Abstract A fourteen year old girl who had had recurrent episodes of cholestatic jaundice and itching since the age of nine years is described. Recurrent seasonal pruritus preceded the onset of jaundice by eight years. No evidence of extrahepatic biliary obstruction could be found despite two surgical explorations. A correlation between the patients serum bile acid levels and pruritus was strongly suggested. It was found that cholestyramine, when given in adequate dosage, decreased the patients abnormally increased serum bile acid concentration and relieved the pruritus. These changes were accompanied by a decrease in the serum alkaline phosphatase and total bilirubin; bromsulfalein retention was no longer abnormal and there was no histologic evidence of cholestasis. Following discontinuation of cholestyramine therapy for a period of thirty-four days there was a significant increase in only the serum alkaline phosphatase activity, although there was moderate pruritus in the latter part of this period; this was again observed during a second period of discontinuation of cholestyramine therapy.

Chronic lactic acidosis of infancy

A 6-month-old girl was followed until age 14 months because of recurrent acidosis and found to have chronically elevated serum and urinary concentrations of lactate, pyruvate, and alpha ketoglutarate. Abnormalities in the patient not described in previous patients with chronic lactic acidosis were anemia with spiculated erythrocytes, nuclear cataracts, and spongy degeneration of the brain. The biochemical findings suggest a deficiency of a factor necessary for the normal decarboxylation of pyruvate. Because of the biochemical similarities of chronic lactic acidosis to conditions of thiamine deficiency and altered thiamine metabolism, and because thamine concentrations in serum and red blood cells of other patients with chronic lactic acidosis have been normal, a defect in thiamine metabolism is postulated.

Amyloidosis in childhood

A case of secondary amyloidosis occurring in a girl who had progressive juvenile rheumatoid arthritis and had been treated intermittently with corticosteroids is presented. Seventy-six cases of amyloidosis occurring in individuals less than 18 years of age were selected from the literature for review. The underlying illnesses, historical data, physical findings, and laboratory data of these patients are discussed, as well as the relationship of corticosteroid therapy in juvenile rheumatoid arthritis to the development of amyloidosis.

Type VI glycogenosis: Biochemical demonstration of liver phosphorylase deficiency

Abstract A boy with hepatomegaly had increased glycogen and low activity of liver phosphorylase. Muscle tissue was normal. Conversion of rabbit muscle phosphorylase b to phosphorylase a by his liver homogenate indicated its normal capacity for phosphorylase activation. The patients hepatic homogenate failed to develop phosphorylase activity under conditions that in control homogenates revealed the presence of endogenous phosphorylase through its activation. The failure was not corrected by the addition of phosphorylase kinase to the patients homogenate. The results indicate liver phosphorylase deficiency or type VI glycogenosis.

Pernicious anemia in the second decade of life

Summary A 13-year-old Caucasian boy who had pernicousanemia with normal gastric acidity and a normal gastric biopsy is described. Although these findings are characteristic of the congenital form of pernicous anemia, it is unlikely that he was born with absence of intrinsic factor since he was 13 years of age at the time symptoms of a deficiency of vitamin B12 developed.

Lysosomal Diseases and Fibroblast Cultures: Biochemical and Electron Microscopic Observations

Most lysosomal diseases are fatal, often after a protracted downhill course that is painfully apparent to patient, parents and physician. This interim report relates our attempts to treat such patients; and to find ultrastructural and biochemical markers in fibroblast cultures for the study of pathophysiology and treatment of lysosomal disease.

Iron content of teeth in hemosiderosis.

TN THE COURSE of studies on the chemical basis of metal-mordant stains, determinations of the iron content of many tissue specimens have been performed. The results of analysis of teeth from a girl with hypoplastic anemia and transfusional hemosiderosis are reported. A 9-month-old white female was first admitted to the hospital because of anemia. Laboratory studies showed hemoglobin 4.3 Gm. per cent and a red blood count of 1.42 million. Bone marrow aspiration showed normal myeloid and lymphoid cells, but severe depression of the erythroid series. The diagnosis of hypoplastic (pure red cell) anemia was made. Over the next 7 years she received treatment at various times with vitamin B12, folic acid, other vitamins, liver extract, cobalt, ACTH, cortisone, and other medications, as well as blood transfusions at roughly 2-month intervals. Except for one transient response to cortisone, the red count, reticulocyte count, and bone marrow erythroid cell count were persistently reduced. During the total period preceding extraction of the teeth analyzed for iron, she received approximately 21,600 c.c. of blood (estimated 11 Gm. of iron). The course of eruption of her teeth was not detailed. Oin first admission only the upper and lower first incisors were present. Two years later her teeth were noted to be various and, at the age of 3 years 10 months, 6 deciduous teeth were extracted because of caries. Shortly after this, biopsies of skin and bone marrow showed mild hemosiderosis. Two years later, splenectomy and liver biopsy were performed; the liver showed marked, and the spleen moderate, hemosiderosis. When the patient was 7 years 8 months of age, extraction of the following teeth was performed because of caries: deciduous upper left first molar, second molar and canine, upper right first molar and canine and lower right cuspid; permanent upper right first molar and lower left first molar. Procedure: Two of the teeth (identity not recorded) were saved for iron determination. The procedure was performed by a modification of the method of Gubler, Lahey, Chase, Cartwright, and Wintrobe.1 The teeth were crushed, weighed, and digested in concentrated sulfuric and nitric acids (2/5 parts). Perchloric acid, nitric acid, and iron-free water were added, and the solution was heated until colorless. Centrifugation for 10 minutes at 2,000 r.p.m. was used to remove CaSO4 crystals, and thioglycolic acid and orthophenanthroline were added to aliquots of the supernatant fluid. The solution was made alkaline with sodium acetate, and the color intensity determined with a Beckman