582

Brief clinical and laboratory observations

been observed in the serum of patients with acute myocardial necrosis or myopathic states,'. ,0. 11 and is not detected in serum following injections, D C counter shock, seizures, or general surgical procedures. 12. 13 A n u m b e r of neurologic disorders including meningitis and encephalitis are associated with elevations of serum C P K . " - l ~ Fractionation of the elevated C P K in such conditions have revealed only C P K - M M (muscle) rather than CPK-BB (brain): 5. 16 The mechanism by which intracranial disorders lead to elevated C P K - M M is unknown; however, this p h e n o m e n o n may have been responsible for the abnormalities of serum C P K in this case. W o o d w a r d 17 has reviewed the unsolved problems in the pathophysiology and clinical m a n a g e m e n t o f R M S F and emphasized that the basic mechanisms o f vascular damage in rickettsial diseases are unknown. Serial measurements of enzymes in patients with R M S F might provide useful information on the incidence and progression of rickettsia-induced tissue damage.

REFERENCES 1. McReynolds EW, and Roy S: An epidemic of tick-borne typhus in children, Am J Dis Child 126:779, 1973. 2. Snape PS: Rocky Mountain spotted fever in Southeastern -United States; A review of eighteen cases from Greenville, South Carolina, South Med J 66:765, 1973. 3. Hand WL, Miller JB, Reinarz JA, and Sanford Jp: Rocky Mountain spotted fever: A vascular disease, Arch Intern Med 125:879 , 1970. 4. Roe CR, Limbird LE, Wagner GS, and Nerenberg ST: Combined isoenzyme analysis in the diagnosis of myocardial injury: Application of electrophoretic methods for the detection and quanfitation of the creatine phosphokinase MB isoenzyme, J Lab Clin Med 80:577, 1972. 5. Rosalki SB: An improved procedure for serum creatine phosphokinase determination, J Lab Clin Med 69:696, 1967.

Hypocomp lementemia in anorexia nervosa Youngki Kim, M.D.,* and Alfred F. Michael, M.D., Minneapolis, Minn.

Aided by grants from the National Institutes of Health (AI 10704 and HL 06314). *Reprint address: Department of Pediatrics, Box 491, University of Minnesota, Minneapolis, Minn. 55455.

The Journal of Pediatrics October 1975

6. Henry RJ, Chiamori N, Golub O J, and Berkman S: Revised spectrophoretic methods for the determinations of glutamic-oxalacetic transaminase, glutamic pyruvic transaminase, and lactic acid dehydrogenase, Am J Clin Pathol 34:381, 1960. 7. Parker RR: Symptomatology and certain other aspects of Rocky Mountain spotted fever, in Moulton FR, editor: The Rickettsial diseases of man, Washington, DC, 1948, American Association for the Advancement of Science, pp 139146. 8. Parker RR: Rocky Mountain spotted fever, JAMA 110:1185, 1273, 1938. 9. Roe CR, Schonberger LB, Gelbach SH, Wies LA, and Sidbury JB: Enzymatic alterations in Reye's syndrome: Prognostic implications, Pediatrics 55:119, 1975. 10. Smith AF: Separation of tissue and serum creatine kinase isoenzymes on polyaerylamide gel slabs, Clin Chim Acta 39:351, 1972. 11. Magalhaes AS: Isoenzymes de la cr6atine-phosphokinase de biopsies musculaires humaines, Acta Neurol Belg 70:471, 1970. 12. Dixon SH, Limbird LE, Roe CR, Wagner GS, Oldham N, and Sabiston DC: Recognition of postoperative acute myocardial infarction: Application of isoenzyme techrfiques, Circulation 47-48 (Suppl 3): 137, 1973. 13. Wagner GS, Roe CR, Limbird LE, Rosati RA, and Wallace AG: The importance of the myocardial-specific isoenzyme of creatine phosphokinase (MB form) in the diagnosis of acute myocardial infarction, Circulation 47:263, 1973. 14. Schiavone DJ, and Kaldor J: Creatine phosphokinase and cerebral disease, Med J Aust 2:790, 1965. 15. Dubo H, Park DC, Pennington RJF, Lalbag RM, and Walton JN: Serum creatine kinase in cases of stroke, head injury and meningitis, Lancet 2:743, 1967. 16. Nevins MA, Laran M, Bright M, and Lyon LJ: Pitfalls in interpreting serum creatine phosphokinase activity, JAMA 224:1382, t973. 17. Woodward TE: A historical account of the rickettsial diseases with a discussion of unsolved problems, J Inf Dis 127:583, 1973.

A N O R E X I A NERVOSA is a psychosomatic disorder with a wide range of metabolic and physiologic derangements. The purpose of this report is to describe an 18-year-old boy with anorexia nervosa who developed hypocomplementemia.

CASE REPORT An 18-year-old white male student was referred to the University of Minnesota Hospital in January, 1974, because of weight loss and a suspicion of kidney disease manifested by mild azotemia and reduced serum level of C3. He had lost 36 pounds (16.4 kg) from his normal weight of 160 pounds (72.7 kg) over a period of approximately 16 months. During this time, he had not had any complaints other than easy fatiguability, recurrent

Volume 87 Number 4

Brief clinical and laboratory observations

583

Table I. Values o f s e r u m proteins a n d c o m p o n e n t s o f the classic c o m p l e m e n t p a t h w a y

Immunochemical assay*

Hemolytic assay

C/s

Date Jan. 1974 Feb, 1974 March 1974 April 1974 May 1974 Sept. 1974 Normal range]

C4 Clq (% reference &gm/ml) serum)

inactivator (% reference serum)

IgG (mg/dl)

IgM (mg/dl)

IgA (mg/dl)

C'H50

CI

C2

Total protein albumin(gm/dl)

63 76 62 95 89 75

78 114 120 172 120 148

65 :~ 66 ~ 81 87 72 95

740 800 -

94 66 --

186 174 -

20 ~ 20 ~ 24 25 26 49

86,0001 105,000~ 83,000 ~ i07,000 ~ 178,000 --

680' 1,310 2,500 1,310 ~' 1,750 -

6.1/3.8 -6.8/4.4 ----

55-123

57-329

70-146

520-1,800

36-280

44-540

23-45

126,000369,000

1,3532,543

5.8-6.8/3.3-4.2

*Modification of radial immunodiffnsion of Mancini using monospeeific antiserum. tNormal age includes values within 2 SD below and above the mean. :~Arrows indicate values below 2 SD from the mean. staphylococcal skin infections of the feet, some leg cramps, and salt craving. He was a very compulsive, achievement-oriented boy, and an outstanding student in school. In adolescence he developed a consuming interest in physical exercise and the nutritional value of foods. In the fall of 1972, he undertook a program of weight reduction by vigorous exercise and restriction of caloric intake to approximately 1,500 calories/day. A dietary history obtained from compulsively kept records revealed that his calories were supplied by approximately 150 gm of protein, 95 gm of carbohydrate, and 64 gm of fat per day. Exercises during this period consisted of long-distance running and weight lifting which were carried out daily. There were no significant prior illnesses. Both parents and six siblings are well. On physical examination, he was found to have no detectable subcutaneous fat with total obliteration of buttock tissue. In addition, a sallow yellow color was noted, particularly evident on. the palms of the hands, but not on the Conjunctivae. He had profound bradyeardia (40/rain), hypothermia (94~ and a slightly low blood pressure (70-120/50-70 mm Hg). The rest of the physical examination was negative. Laboratory values included: hemoglobin concentration 13.5 gm/dl, hematocrit 38.5%, white blood count 3,850/mm 3, neutrophils 65%, lymphocytes 31%, monocytes 4%, adequate platelets, erythroeyte sedimentation rate 3 ram/60 min, normal serum concentrations of electrolytes, serum cholesterol 173 mg/dl, serum triglycerides 42 mg/dl, fasting blood sugar 71 mg/dl, blood urea nitrogen 31 mg/dl, true serum creatinine 0.6 mg/dl, creatinine clearance 140 ml/min/1.73 m 2, negative urinalysis, negative 24-hour urinary excretion of protein, normal liver function studies, serum zinc 125/~g/dl (normal range 80-165/zg/ dl), serum carotene 640/~g/dl (normal range 80-220~g/dl), T4 as I 2.1/Lg/dl (normal range 3.0-7.0/zg/dl), negative fluorescent antinuclear antibody, normal lymphocyte stimulation with phytohemagglutinin, normal chest roentgenogram, normal small and large bowel roentgenograms, abnormal electrocardiogram with sinus bradycardia and inverted T waves in aVL, and negative stool examination for ova and parasites.

The patient was fed a diet of approximately 3,000 calories/day. When he was seen again in September 1974, he was in excellent physical condition with weight gain of 33 pounds (15 kg). The psychiatrist who saw the patient on three occasions during the period of observation concluded that the clinical picture and personality structure were consistent with the diagnosis of anorexia nervosa even though this is a rare entity in adolescent boys. The patient refused ongoing psychotherapy and currently is a freshman in college.

METHODS Hemolytic assays for C'H50, C1, a n d C2, a n d i m m u n o chemical d e t e r m i n a t i o n s o f Clq, C3, F a c t o r B (C3PA), a n d p r o p e r d i n were carried o u t as previously r e p o r t e d ? , I m m u n o c h e m i c a l d e t e r m i n a t i o n s o f Cls Inactivator, C4, IgG, IgA, a n d I g M were carried out b y the M a n c i n i techniqUe 3 using monospecific a n t i s e r u m to h u m a n Cls Inactivator (Behring Diagnostics, Somerville, N e w Jersey) and, antisera to h u m a n C4 a n d specific i m m u n o g l o b u l i n s (Meloy Laboratories, Springfield, Virginia). T o t a l s e r u m protein was m e a s u r e d b y the Biuret reaction, 4 a n d s e r u m a l b u m i n by electrophoresis o n cellulose acetate using H e l e n a zip zone system. To rule out the p r e s e n c e o f a s e r u m factor t h a t activates the c o m p l e m e n t system (C3NeF), one p a r t o f the p a t i e n t ' s s e r u m was m i x e d with four parts o f n o r m a l h u m a n s e r u m a n d i n c u b a t e d at 37~ for 30 minutes a s described b y Vallota a n d associates. 5 I m m u n o e l e c t r o p h o r e s i s was carried out using m o n o specific a n t i - h u m a n C3 a n d a n t i - h u m a n F a c t o r B. RESULTS T h e r e was a significant r e d u c t i o n in the c o n c e n t r a t i o n o f C1, C2, C3, Cls Inactivator, F a c t o r B, a n d total hemolytic c o m p l e m e n t in initial s e r u m specimens (Fig. 1,

584

Brief clinical and laboratory observations

.~ ~ 200

-~-

The Journal of Pediatrics October 1975

-~

5~ ~z~-

40

300~50"

....~ . .~, ~..r.~,~,~. ~. ,~.~..~,~m...,z.~.~ ~..-.~7~...,.,:~.~.-. ~.~. ~ : ~ .

"~

100"

751

7O

6O

I

/

f

J.4N FEB M.~.R .4~~ M/IY JI)N JUL

AI~IG

SEP

1974 Fig. 1. The relationship of the patient's weight and serum levels of components of the alternate complement pathway. Shaded area represents mean _+ 2 SD. Table I). Serum levels of Clq, C4, properdin, IgG, IgA, IgM, albumin, and total protein were within normal limits. There was a gradual increase in the level of serum complement components as the patient gained weight. By the time the patient had regained his normal weight 8 months later, the serum levels of all complement components had returned to normal. No C3NeF activity was detected in the patient's serum. DISCUSSION There is a striking similarity in the clinical and laboratory findings in patients with anorexia nervosa and victims of starvation. ~. 7 This implies that many of the manifestations of anorexia nervosa are a reflection of starvation. Reduction of the serum complement proteins have previously been reported in malnourished children. 8-~~In a study of 20 children with protein-calorie malnutrition, Sirisinha, and associates 1~found a significant reduction of

serum complement components when compared to normal children. Whereas only serum C5, C6, and Factor B were decreased in marasmus, patients with kwashiorkor showed a reduction of eight serum complement proteins: Clq, Cls, C3, C5, C6, C8, C9, and Factor B. Our patient with anorexia nervosa had decreased serum levels of C 1, C2, C3; Cls Inactivator, and F a c t o r B, whereas serum values for Clq, C4, and properdin remained normal. Our patient exhibited a unique interest in the nutritional value of foods, which led him to limit his caloric intake to approximately 1,500 calories/day while maintaining an adequate daily protein intake of 2 gm/kg. During this period of time he continued an intense and regimer~ted exercise program which included daily weight lifting and long-distance running. Levels of complement components returned to normal simply by increasing his caloric intake to 3,000 calories/day. In the study by Sirisinha, and associates ~~an increase in the serum level of complement components to normal was observed in patients with protein-calorie malnutrition who were treated with a high protein, maintenance caloric diet, but not with a high calorie, maintenance protein diet. They concluded that the amount of protein intake seemed to exert more influence on serum complement components than calorie intake. The findings in our patient, however, dearly indicate that inadequate calorie intake alone can lead to a reduction of the serum complement proteins. It is of interest that a significant reduction in the levels of other serum proteins-immunoglobulins and albumin-was not observed at a time when hypocomplementemia was present. This may reflect differences in the synthetic and catabolic rates of individual proteins. The complement system plays an important role in the host's resistance to infection. Both the classic and alternate complement pathways are involved in chemotaxis and opsonization. TM 12 Our patient had a history of recurrent staphylococcal skin infections which could have been caused by the complement abnormalities described in this report. REFERENCES

1. Day NK, Geiger H, McLean RH, Michael AF, and Good RA: C2 deficiency. Development of lupus erythematosus, J Clin Invest 52:1601, 1973. 2. McLean RH, and Michael AF: Properdin and C3 proactivator. Alternate pathway components in human glomerulonephritis, J Clin Invest 52:634, 1973. 3. Mancini G, Carbonara AO, and Heremans JF: Immunochemical quantitation of antigens by single radial immunodiffusion, Immunochemistry 2:235, 1965. 4. Weichselbaum TE: An accurate and rapid method for the determination of proteins in small amounts of blood serum and plasma, Am J Clin Pathol 10:40, 1946. 5. Vallota EH, Grtze O, Spiegelberg HL, Forristal J, West CD, and Mt~ller-Eberhard H J: A serum factor in chronic hypo-

Volume 87 Number 4

6.

7. 8. 9.

Brief cBnical and laboratory observations

585

complementemic nephritis distinct from immunoglobulins and activating the alternate pathway of complement, J Exp Med 139:1249, 1974. Warren MP, and Vande Wiele RL: Clinical and metabolic features of anorexia nervosa, Am J Obstet Gynecol 117:435, 1973. Silverman JA: Anorexia nervosa. Clinical observations in a successful treatment plan, J PEDIATR84:68, 1974. Chandra RK: Immunocompetence in undernutrition, J PEDIATR81:1194, 1972. Smythe PM, Schonland M, Brereton-Stiles GG, Coovadia HM, Grace H J, Loening WEK, Mafoyane A, Parent MA, and Vos GH: Thymolymphatic deficiency and depression

of cell-mediated immunity in protein-calorie malnutrition, Lancet 2:939, 1971. 10. Sirisinha S, Suskind R, Edelman R, Charupatana C, and Olson RE: Complement and C3 practivator levels in children with protein-calorie malnutrition and effect of dietary treatment, Lancet 1:1016, 1973. 11. Clark PA, Frank MM, and Kimball MR: Generation of chemotactic factors in guinea pig serum via activation of the classical and alternate complement pathways, Clin Immunol Immunopathol 1:414, 1973. 12. Winkelstein JA: Opsonins. Their function, identity, and clinical significance, J PEDIATR82:747, 1973.

Hypothalamic-pituitary function in the fetal alcohol syndrome

measured by radioimmunoassay (Bio Science), 1~ and plasma cortisol levels were determined by fluorometry? 3 Bone age was assessed by roentgenograms of the wrists and hands. TM Other laboratory studies were performed in the chemistry laboratory of the All Children's Hospital employing conventional methods. Psychologic evaluation was performed employing the Wechsler intelligence scale for children.

Allen W. Root, M.D., Edward O. Reiter, M.D., Mary Andriola, M.D., and Gregory Duckett, B.S., St. Petersburg, Fla. M A T E R N A L INGESTION OF ALCOHOL appears to be the cause of a pattern of congenital anomalies in the offspring which includes prenatal and postnatal growth retardation, microcephaly, dysmorphic facies, microphthalmia, ptosis, strabismus, abnormalities o f limbs, heart, and genitals, and psychomotor retardation, with frequency of impaired intellectual performance increasing with age. 1-6 Several families have been reported recently 6' 6 in which more than one infant of an alcoholic mother has been affected. Studies of the function of the hypothalamic-pituitary axis were undertaken in four children (9 to 15 years of age) born to an alcoholic w o m a n in order to determine if a hormonal abnormality may account for the aberrant growth patterns characteristic of the fetal alcohol syndrome.

MATERIALS AND METHODS The serum concentrations o f h G H , insulin, LH, F S H , and P T H were determined by double antibody radioimmunoassays. 7-11 Plasma testosterone concentrations were

From the Departments of Pediatrics, University of South Florida College of Medicine, The University of Florida, and the Ed Wright Pediatric Endocrinology Research Laboratory, All Children's Hospital. S.upported by United States Public Health Service Grant HD 08313 and the National Foundation-March of Dimes.

Abbreviations used ACTH: : adrenocorticotropic hormone follicle-stimulating hormone FSH: human growth hormone hGH: LDH: lactic acid dehydrogenase luteinizing hormone LH: LH-RH: LH-releasing hormone parathyroid hormone PTH: SGOT: serum glutamic oxaloacetic transaminase SGPT: serum glutamic pyruvic transaminase

CASE REPORTS The four children were born to a gravida 5, para 5 woman who died at 48 years of age of hepatic failure and bleeding esophageal varices secondary to chronic alcoholic cirrhosis. Mrs. C. had been a severe alcoholic for many years prior to the birth of her first child at 34 years. Her exact alcoholic consumption prior to and during her pregnancies is unknown but in the months prior to death it is reported that Mrs. C. consumed from 1.2 to 1.6 gallons of liquor daily. Mrs. C's first pregnancy terminated in the premature birth of an infant who died shortly after birth. No details concerning this child are available. Birth data and anthropometric findings in the four remaining children are presented in Tables I and II, respectively. The children had many features in common, though Patient P. C. seemed least affected. All of the children were of low birth weight and experienced delayed growth postnatally. Three (Patients K. C., A. C., P. C.) were underweight for height. The facies of Patients K. C., A. C., and R. C. were dolichocephalic with maxillary hypoplasia, short palpebral fissures, ptosis, and micrognathia, whereas Patient P. C. had fewer dysmorphic