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The Journal
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steps in the urea cycle is provided by the very low plasma citrulline levels observed in the face of overwhelming hyperammonem ia. It is important to be aware of the potential development of severe aberrations of metabolism involving pathways other than the one in which a primary enzyme defect lies. Severe hyperammonemia and hyperlysinernia may occur in patients with methylmalonyl-CoA mutase deficiency. This combination should now be considered in the context of the occurrence of hyperlysinemia and organic acidemia reported in urea cycle disorders, and the occurrence of hyperammonemia in disturbances of lysine metabolism,"" nonketotic hyperglycinemia, and in primary organic acidemias.« n. 11 A careful biochemical differential diagnosis may facilitate appropriate patient and family management. ADDENDUM
Since the preparation of this manuscript, an additional case of severe hyperarnmonemia occurring in an infant with methylmalonyl-Co.A mutase deficiency has been reported.': The authors thank Dr. M. J. Mahoney, New Haven, Conn., for performing the fibroblast methylmalonyl-CoA mutase assays. REFERENCES
J. Shih VE, and Efron ML: The urea cycle disorders, in Stanbury JB, Wyngaarden JB, and Fredrickson DS, editors: The metabolic basis of inherited disease, ed 3, New York, 1972, McGraw-Hill Book Company, p 370. 2. Gompertz, D, Bac DCK, Storrs CN, and Peters JJ: Localization of enzyme defect in propionicacidemia, Lancet 1:1140, 1970. 3. KeatingJP, Feigin RD, Tenenbaum SM, and Hillman RE: Hyperglycinemia with ketosis due to a defect in isoleucine metabolism: A preliminary report, Pediatrics 50:890, 1972.
4. Morrow G, Barness LA, Auerback YH, DiGeorge AM, Ando T, and Nyhan WL: Observations on the coexistence of methylmalonic acidemia and glycinemia, .T PrmlATR 74:680, 1969. 5. Boisse J, Perelman R, Rudler .IC, Charpentier C, and Pousset JP: L'Acidemie methylrnaloniquc. Une cause nouvelle d'acidocetose grave, Ann Pcdiatr 18:53, 1971. 6. Landes RD, Avery GB, Walker FA, and Hsia YE: Propionyl-CoA carboxylase deficiency (proplonicacidemia): another cause of hyperammonemia, Pediatr Res 6:394, 1962. 7. ColumboJP, Yassella P, Humbel R. and Buergi W: Lysine intolerance with periodic ammonia intoxication, Am .T Dis Child 113: 138. 1967. 8. Ghadimi H, Kottmeier P, Achs R, Prabbu R, and Jaffe B: Hereditary hyperlysinemia and lysine-induced crises, Proceedings Society Pediatric Research 35th Annual Meeting, Philadelphia, 1965, p 33 (ahstr). 9. Kekomuki M, Vlsakorpi .IK, Pcrhccntupn .I, and Saxon L: Familial protein intolerance with dctlcieut transport of basic amino acids, Acta Paediutr Scund 56:617, 1967. 10. Brown .TH. Fabre LF .II', Farrell GL, and Adams ED: Hyperlysinuria with hypcrummonemin, Am .I Dis Child 124:127,1972. II. Kung, ES, Snodgrass 1'.1, and Gerald P: MethylmalonylCoAracemasedefect: another cause or mcthylmulonicaciduria, Pediulr Res 6:875, 1972. 12. Halperin ML, Schiller eM, and Fritz IB: The inhibition by methylmalonlc acid of malate transport by the dicarboxylate carrier in rat liver mctochondriu, .I Clin Invest 50:2276, 1971. 13. Patel MS, Owen DE, and Raefsky C: EIl'ect of mcthylrnulonatc on ketone body mctubclism in developing bruin, Life Sci 19:41, 1976. 14. Cheerna-Dhadli S. Leznolf Cc. and Halperin M L: Effect of 2-methylcitrate on citrate metabolism: implications for the management of patients with propionic aciduria and methyl malonic aciduria, Pediutr Res 9:905. 1975. 15. Packman S. Mahoney M.I. Tanaka K. and Hsiu YE: Severe hyperammonemia in a newborn infant with methylrnalo nyl-Coa mutase deficiency. J PEDIATR 92:769. 1978.
Pseudodiverticulitis Of the appendix with neonatal Hirschsprung disease Maurice N. Srouji, M.D.,* Jane Chatten, M.D., and Cynthia David, M.D., Philadelphia, Pa.
is an infrequent complication of neonatal Hirschsprung disease, attributed to distal func-
BOWEL PERFO RA TION
From the Departments ofSurgery, Pathology. and Radiology, Tile Children's Hospital of Phi/adelphia, and The School of Medicine, University of Pennsvlvania, "Reprint address: The Childrens' Hospital of Philadelphia, 34th St. and Civic Center st-«, Philadelphia, fA 19104.
tional obstruction and proximal luminal distention causing ischemic necrosis of the bowel wall.' N eona tal a ppendiceal perforation with Hirschsprung disease has been reported with abscess formation and, also, without significant gross inflammation? Pseudodiverticula of the appendix have occurred in adults with 01' without inflammation and with or without associated appendicitis or perforation with periappendicitis.": Increased intralumi0022-3476178/120988 +03$00.30/0 (0 1978 The C. V. Mosby Co.
Volume 93 Number 6
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Figure. Microphotograph of intact appendiceal mucosa (upper left), neck of pseudodiverticulurn interrupting the muscularis (M), and triangular lumen of the ulcerated pseudodiveruculum in the heavily inflamed mesoappendix (right). (Hemotoxylin and eosin original; X 50.)
nal disterition and muscular contraction have been implicated in the parhogenesis.r" We are not aware of previous reports on pseudodiverticulum of the appendix in infants. A patient with total aganglionosis of the colon with appendiceal pseudodiverticulitis and periappendicitis is presented. CASE REPORT A 4-week-old boy presented with persistent refusal to feed, abdominal distention. obstipation, and radiographic evidence of fluid levels and colonic fecal impaction. He had gradually developed anorexia, decreased frequency of bowel movements, and straining on passing firm stools. On admission there was mild dehydration, low-grade fever, and moderate leukocytosis. After clinical improvement, a barium enema was performed. The small bowel was distended and the colon appeared shortened but had a normal caliber with appreciable fecal contents. During a two-day follow-up there was no evacuation of the barium which, instead, moved in retrograde fashion into the dilated ileum. The radiographic diagnosis was total aganglionosis of the colon. On exploration at the age of 32 days there was barium impaction in the bowel. The distal ileum was dilated and thickened. The
appendix was only 4 ern in length and widened to 2 em in diameter. It appeared firm but normal in color while the mesoappendix was congested and indurated. Multiple frozen and subsequent permanent sections of the proximal colon and distal ileum demonstrated agauglionosis of the colon. The ileocecal segment was resected leaving a colonic external mucus fistula and a temporary ileostomy. Microscopic examination of the appendix (Figure) revealed an ulcerated pseudodiverticulum within the inflamed mesoappendix. Otherwise, the appendiceal lumen and wall were normal. The infant developed satisfactorily and the Martin modification of the Duhamel procedure was performed uneventfully at the age of one year.
COMMENTS True (congenital) diverticula form only 3% of about 1,400 cases of diverticular disease of the appendix:' Only seven were found in the pediatric age group and all were in premature or newborn infants with multiple appendiceal diverticula and multiple organ anomalies attributed to trisomy D(l3-15).7 Pseudodiverticula, on the other hand, represent acquired herniations of the mucosa and
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The Journal of Pediatrics December 1978
Brief clinical and laboratory observations
submucosa through a muscular defect in the appendiceal wall, presumably, at the site of blood vessels. Experimental and clinical evidence favors high pres sure in the appendiceal lumen as the important underlying pathogenic mechanism ." 6. ' In this infant , pathophysiologic factors ind icating an increase in appendiceal luminal tension were distal functional obstruct ion by aganglionosis and barium impaction and the hypertrophy of the distal ileum. In the review of Trollope and Lindenauer' on diverticulosis of the appendix there were no reported cases of pseudodiverticula (acquired) in the infant age group. It is probable that the same mechanism(s) applies in perforation of the colon, cecum, and appendix complicating Hirschsprung disease. Increased intraluminal pressure proximal to the functi onal obstruction causes dilatation and thinn ing of the bowel wall before the onset of hypertrophic changes . This can conceivably induce development of pseudodiverticula and rupture without necessarily implicating local ischemic necrosis. The narrow neck and thin wall make an appendiceal pseudodiverticulum more susceptible than the appendix itself to obstruction, inflammation, and perforation." 8 Martin and Perrin" reported three infants with neonatal appendiceal perforation associated with Hirschsprung disease. One infant had an appendiceal abscess but in the other two perforation was found without significant gross inflammation. The association, however , is difficult to assess because reports on neonatal appendicitis do not include postmortem search for aganglionosis nor long-term follow-up. Gastrin and Josephson" reported an appendiceal abscess with peritonitis in a newborn infant who,
after repeated episodes of subacute bowel obstruction, was found at the age of 2 years to have aganglionosis of the distal half of the colon. The funnel configuration and the relative sparsity of lymphoid tissue in the appendix of the newborn infant make it less vulnerable to intraluminal obstruction, a major pathogenic factor in the usual acute appendicitis. This suggests the possibility of an unrecognized more frequent association of appendicitis in newborn infants with distal functional obstruction of the colon. REFERENCES 1. Ephrenprels T: Hirschsprung's disease , Chicago , 1970, Year Book Medical Publishers , Inc., p 64. 2. Martin LW, and Perrin EV: Neon atal perforation of the appendix in association with Hirschsprung's disease , Ann Surg 166:799 , 1967. 3. Deschenes L. Couture J , and Garneau R : Diverticulitis of the ap pendix, Am JT Surg 121:706, 1971. 4. Trollope ML , and Lindenauer SM: Diverticulosis of the appendix: A collective review, Dis Colon Rectum 17:200, 1974. 5. Stout AP: A study of d iverticul um formation in the appendix, Arch Surg 6:793, J923. 6. Buirge RE, Dennis C, Varco RL , et al : Histology of experimental appendiceal obstruction (rabbit, ape and man), Arch Pathol 30:481 , 1940. 7. Favara BE: Multiple congenital diverti cula of the verrniform appendix, Am J Clin Pathol 49:60, 1968. 8. Rabinovitch J, Arlen D, Barnett T, et al: D iverticulosis and diverticulitis of the vermiform appendix, Ann Surg 155:434, 1962. 9. Gastrin U, and Josephson S: Appendiceal peritonitis and megacolon in the neonatal period , Acta Chir Scand 136: 153, 1970.
Varicella arthritis documented by isolation of virus from joint fluid John R. Priest, M.D.,· M inneapolis, Minn. , James J. Urick, M.D ., A listin, Minn., Karl E. Groth, B.S., and Henry H. Balfour, Jr., M.D., Minneapolis, Minn.
From the Departments of Pediatrics and of Laboratory Medicine and Pathology, University of Minnesota Health Sciences Center, and the Austin Medical Clinic, P.A. Supported in part by Public Health Service grant
A M18883. 'Reprint address: Box 56, Mayo Memorial Bldg; University of Minnesota Health Sciences Center, Minneapolis, MN 55455.
both bacteria\" 2 and nonbacterial.v" ha s been reported as a rare complication of varicella infection in children. The arthritis is manifested as a swollen,
ARTHRITIS,
Abbreviation used VZV: varicella-zoster virus
inflamed joint appearing within a week after the onset of a varicella rash. Bacterial arthritis is thought to result from 0022-3476178 /120990 + 03$00.30 /0
e
1978 The C. V. Mosby Co.