Familial Asplenia, Other Malformations, and Sudden Death

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EXPERIENCE AND REASON 633 ACKNOWLEDGMENTS

We wish to thank James Driscoll, PhD, Department of

Biochemistry, Rhode Island Hospital, for technical

as-sistance and Ms Donna Perry for secretarial assistance.

REFERENCES

PAUL A. PITEL, MD

KENNETH L. MCCORMICK, MD

EILEEN FITZGERALD, MD

JAY M. OisoN, MD

Rhode Island Hospital and

Brown University

Providence, Rhode Island

1. Krugman 5, Ward R (eds): Infectious Diseases of Children, ed 4. St Louis, CV Mosby Co, 1973, p 412

2. Huttenlocker PR: Reye’s syndrome: Relation of outcome to therapy. J Pediatr 80:845, 1972

3. Vaughan VC, McKay JR (eds): Nelson Textbook of Pedi-atrics, ed 10. Philadelphia, WB Saunders Co, 1975, p 671

4. Landay SG: Varicella hepatitis and Reye’s syndrome: An

interrelationship? Pediatrics 60:746, 1977

5. Hoeprich PD (ed): Infectious Diseases. New York, Harper

and Row Publishers, Inc, 1977, p 750

6. Seligson D, Hirahara K: The measurement of ammonia in

whole blood, erythrocytes, and plasma. J Lab Clin Med 49:

962, 1957

7. Eschar J, Teit L, Waron M, et al: Hepatic lesion in chicken

pox. Gastroenterology 64:462, 1973

8. Cheatham WJ, Weller TH, Dolan TF, et al: Varicella: Report

of two fatal cases with necropsy, virus isolation and serologic studies. Am J Pathol 32:1015, 1956

9. Stanton RE, J005 HA: Glutamic-oxalocete transaminase of

serum in infancy and childhood. Pediatrics 24:352, 1959

10. Seaman WE, Ishak KG, Plotz PH: Aspirin-induced

hepato-toxicity in patients with systemic lupus erythematosis. Ann

Intern Med 80:1, 1974

Familial

Asplenia,

Other

Malformations,

and

Sudden

Death

Sometimes the sudden, unexpected death of an

infant is shown by necropsy to be associated with

a clinical entity more clearly defined than sudden

infant death syndrome. This is a report of two

unrelated families, each with two affected members.

In one, asplenia occurred with and without

gastroin-testinal malformations. In the other, cardiovascular

malformations occurred in one member and

lye-mark syndrome’ in the other. Each asplenic infant

died suddenly.

CASE REPORTS

Case 1

I. H., a 7-month-old girl was in good health until fever,

cough, and irritability appeared three days before death.

On postmortem examination, no spleen was detected.

There were no other malformations. The respiratory sys-tern showed congestion of the entire airway. The pulmo-nary arteries were filled with large mononuclear cells and

fibrin that appeared as compact thrombi propagating

from congested larger arteries into small branches. The septa were widened, and their cellularity was increased.

There were a few air spaces with amorphous eosinophiic

material. The brain also showed multiple microthrombi

composed of large mononuclear cells and fibrin.

Postmor-tern bacteriologic culture showed only a rare colony of

Enterobacter. Studies for virus infection showed no

growth.

Case 2

A 1-year-old girl, C. K., died after 24 hours of fever.

Four months previously, she had been treated for a

serious sickness involving shock and hematologic

evi-dence of disseminated intravascular clotting, but with no

growth in a blood culture. At 2 weeks of age, surgery had

been performed on this infant to correct a herniation of

the stomach through the foramen of Bochdalek into the

right hemithorax.

Postmortem examination showed the large intestine to

be imperfectly rotated with the sigmoid largely toward

the midline but stifi on the left. The stomach was in the

right upper quadrant. The liver lay across the upper

abdomen with the right and left lobes approximately the

same size. The gallbladder arose from the right lobe. A

spleen could not be identified. The left diaphragm was

intact. The heart, great vessels, and coronary arteries were entirely unremarkable.

There was no consanguinity in this family, but the

greatgrandmothers of the two cases were sisters.

Case 3

Publication of this article was unavoidably delayed by adminis-trative problems.

Reprint requests to (A.L.K.) Hunterdon Medical Center,

Fle-mington, NJ 08822.

The first child in the family was a girl, N. G., who

became cyanotic shortly after birth. Catheterization and

angiographic studies showed transposition of the great

arteries plus the presence of subpulmonary stenosis of a

mild degree. A normal spleen and splenic artery were

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634 PEDIATRICS Vol. 65 No. 3 March 1980

visualized. An atrial septostomy was performed, followed

at a later date by a Mustard procedure.

Case 4

B. G., N. G.’s younger male sibling, also developed

cyanosis. Study at St. Christopher’s Hospital,

Philadel-phia, demonstrated a common atrium and single

ventri-cle; from it an anterior aorta arose. There was a posterior

small pulmonary artery with two branches and a persist-ent left superior vena cava and a right superior vena cava. The stomach was on the right side. Howell-Jolly bodies were present on the blood smear. Eight days after

pallia-tive surgery, the infant died abruptly at 2 months of age

with respiratory distress but no definite evidence of sepsis.

There was no spleen present.

Consanguinity could not be demonstrated.

DISCUSSION

Simpson and Zellweger2 described two siblings

with Ivemark syndrome. Rose and co-workers3 have

found no significant association with maternal or

paternal age. The recurrence rate in all the siblings

of their patients with asplenia syndrome was 4.65%.

Waldman et al4 reported two members of one family

with the asplenia syndrome. Chen and Monteleone5

reported two families with variable inheritance.

Alonso and Dew6 reported single ovum twins with

congenital cardiovascular malformations; one had

a spleen, the other did not. Kevy and co-workers7

have reported a family in which three of the five

children had very diminutive spleens but no other

malformations. DeLeon8 noted triplets of whom two

were conjoined twins; one had many malformations

and had no spleen. Asplenia associated with

hemi-melia but not with any other malformations has

been found in a strain of mice, inherited as an

autosomal dominant gene.9

The occurrence of these sibships together with

the findings of consanguinity in some sporadic cases

suggests autosomal recessive inheritance.

Members of the family of cases 1 and 2 have been

advised to have newborn infants studied for

as-plenia by a search for Howell-Jolly bodies. Spleen

scans are to be done if Howell-Jolly bodies are

present. Five infants have been subsequently born

to members of this family; all are normal. Case 4 in

the second family illustrates the need to be aware

of the possibility of asplenia-polysplenia in patients

with complex cardiac malformations. Death may be

related to sepsis rather than insufficient pulmonary

perfusion or congestive heart failure.’4

Indications for a search for asplenia are ( 1)

his-tory of a family member with asplenia or

polysple-nia; (2) presence of complex cardiac malformations

such as transposition, single ventricle, common

atrium, anomalous pulmonary venous return,

bilat-eral superior venae cavae, or aortic anomalies; (3)

presence of visceral heterotaxy or other associated

malformations; and (4) appearance of eparterial

bronchi or bilateral trilobed or bibbed lungs on a

roentgenogram. Infants with any of these elements

in their history should have a blood smear for

Howell-Jolly bodies. In questionable cases, a spleen

scan should be performed. Radiographic study of

chest and abdomen should be used to identify

ab-normal lobulation of lungs, position of bronchi,

cardiac shadow, or visceral heterotaxy.

Infants recognized as having asplenia or

polysple-nia should be protected with prophylactic

penicil-un.4 Ampicillin should be considered for children

under the age of 10 and penicillin V for other

children. Medications should be given twice daily.

The duration of prophylactic treatment is not now

known.4 Pneumococcal polysaccharide vaccine

should be used for children over the age of 2 years,

although specific proof of its efficacy in this

condi-tion is not available. The use of pneumococcal

polysaccharide vaccine in children is not followed

by significant reactions.’#{176}

SUMMARY

Two families have been presented. In one,

as-plenia occurred with and without gastrointestinal

malformations. In the other, cardiovascular

malfor-mations occurred in one member and Ivemark

syn-drome in the other. All three children with asplenia

died in infancy, two with evidence of sepsis. Sudden

death in infancy may be due to sepsis in a child

with isolated asplenia syndrome and impaired

re-sistance to infection. Both isolated asplenia and

some cases of congenital heart disease without

as-plenia may be related to Ivemark syndrome.

New infants born in families with a history of

congenital cardiovascular malformations, visceral

heterotaxy, or other malformations associated with

Ivemark syndrome should be tested for asplenia,

primarily by searching for Howell-Jolly bodies.

In-fants with asplenia should be protected with

pro-phylactic antibiotics. Pneumococcal polysaccharide

vaccine is indicated at the age of 2 years.

It would appear worthwhile for pediatric surgical

or pediatric cardiologic services to perform a

screen-ing program for Howell-Jolly bodies.

ACKNOWLEDGMENTS

We thank Dr I. F. S. Black ofSt. Christopher’s Hospital

in Philadelphia for providing information on cases 3 and

4 and Dr C. F. Barneh for providing information on case

2. We also appreiate the helpful comments of Drs

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EXPERIENCE AND REASON 635

Liang Lee, Michael McCormick, Photinea Papageorgio,

Richard Rapkin, and Norman Sissman, of Rutgers Med.

ical School, and Theodore Kushnick of the New Jersey

Medical School.

REFERENCES

AVRUM L. KATCHER, MD

Hunterdon Medical Center

Flemington, New Jersey

and

Rutgers Medical School

Piscataway, New Jersey

1. Ivemark B: Implications of agenesis of the spleen on patho-genesis of cono-truncus anomalies in childhood. Acta

Pae-diatr Scand 44(suppl 104):000, 1955

2. Simpson J, Zellweger H: Familial occurrence of Ivemark

syndrome with splenic hypoplasia and asplenia in sibs. J Med Genet 10:303, 1973

3. Rose V, et a!: Syndromes of asplenia and polysplenia: A review of cardiac and non-cardiac malformations in 60 cases

with special reference to diagnosis and prognosis. Br Heart

J37:840, 1975

4. Waldman JD, et al: Sepsis and congenital asplenia. JPediatr

90:555, 1977

5. Chen SC, Monteleone PL: Familial splenic anomaly

syn-drome. J Pediatr 91:160, 1977

6. Alonso K, Dew JM: Cor bioculare: Report of congenital heart disease in twins. J Med Assoc G 64:420, 1975 7. Kevy SU, et al: Hereditary splenic hypopla.sia. Pediatrics

42:752, 1968

8. DeLeon F: Siamesiche Zwilhinge mit differenten bildengen. Virchows Arch 362:51, 1974

9. Searle AG: Hereditary absence of spleen in the mouse.

Nature 184:1419, 1959

10. Klein JO, Mortimer EA: Use of pneumococcal vaccines in children. Pediatrics 61:321, 1978

THE ONLY PRIVILEGED PEOPLE

Most children in the Third world are under.fed and ifi-educated. The

young-sters of Cuba are an exception. I asked the waiter in the hotel for orange juice

at breakfast on my first morning in Cuba, some 10 years ago. ‘Only for children,’

he said. One of the official slogans then was, ‘Children are the only privileged

people,’ and only families with a child under eight could have any of the rationed

supply of orange juice.

This year orange juice, though stifi rationed, is available to everyone, but

there’s still a slogan, ‘There is nothing more important than a child.’

To arrive in Cuba from another Latin American country is to notice right

away the difference in the condition of the children. No ricketty little beggars

materialize by your table and stare piteously at your food. Every child in the

street looks adequately fed. There is none of that dull-eyed listlessness which

signals mental deficiency due to bad diet and lack of stimulation, and which

dooms tens of millions of kids to a short life and a wretched one.

In 20 years, since the Castro revolution, Cuba has brought up a generation in

health and opportunity. No amount of critique and qualification can detract

from this liberation of a previously beset majority of a nation from the withering

fears which blight most of humanity. Mothers are free of basic fears for the fate

of their children-come what may, they will be fed and, if they fall ill, proper

medical care will be available at no charge. There will be free education for

them and, if they have the right talents and application, they will be able to

attain any position in society. The infant mortality rate is lower than in many

parts of the United States. All this has been brought to pass in an agricultural,

tropical country of 10 million people, more than half of whom are aged under

16.

From John Erril: The only privileged people. The Observer, Sunday September 2, 1979.

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1980;65;633

Pediatrics

Avrum L. Katcher