Abetalipoproteinemia Presenting as Severe Vitamin K Deficiency

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EXPERIENCE AND REASON 161

Abetalipoproteinemia

Presenting

as Severe

Vitamin

K Deficiency

Vitamin K deficiency has occasionally been

ob-served in infants after the immediate neonatal

pe-nod when one or more of the following features is

present: diet consisting entirely of breast milk,

fail-ure to receive prophylactic vitamin K shortly after

birth, therapy with broad-spectrum antibiotics, or

chronic diarrhea accompanying malabsorption due

to cystic fibrosis or to various acquired causes.’7 In

this report we describe for the first time an infant

with the uncommon autosomal recessive disorder

abetalipoproteinemia whose major presenting

man-ifestation in early infancy was hemorrhage due to

vitamin K deficiency.

CASE REPORT

A 6-week-old baby was brought in for evaluation

be-cause of a two- to three-week history of easy bruising. Past history included a normal pregnancy, labor, and delivery. The birth weight was 2,900 gm, and there were

no perinatal problems. Prophylactic intramuscular

vi-tamin K was not administered after birth, in accordance with the custom at the small hospital where the child was born. His diet consisted exclusively of breast milk. Al-though he had been active and his appetite seemed good, he was noted to have poor weight gain. He was receiving

no antibiotics or other medications and had no history of

diarrhea.

Physical examination revealed a thin 2,785-gm infant

with numerous ecchymotic lesions on his chest wall, face,

and extremities (Figure). He bled profusely from multiple

venipuncture sites. Laboratory studies included a

hemo-globin of 10.1 gm/100 ml, hematocnt of33%, normal total

and differential white blood cell count, and platelet count of 780,000/id. His stool was positive for occult blood. The

prothrombin time (PT) was 51 seconds (normal, 1 1 to 14

seconds), and the activated partial thromboplastin time (PTT) was 193 seconds (normal, 25 to 35 seconds).

Fol-lowing treatment with 5 mg of intravenous vitamin K1

there was an immediate cessation of hemorrhage. Four

hours later his PT and PTT were 1 1.9 and 32.5 seconds,

respectively.

Investigation of his failure to thrive and vitamin K deficiency included a normal sweat chloride

determina-tion (9 mEq/liter) and normal values for tests of liver

function. It was then appreciated for the first time that

50% to 75% of the red blood cells on his peripheral blood

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smear were acanthocytes, dense cells with prominent thorny projections. Serum cholesterol level was only 49

mg/100 ml, and the triglycerides level was 10 mg/100 ml,

both markedly diminished values. The diagnosis of

abe-talipoproteinemia was then confirmed by lipoprotein elec-trophoresis demonstrating the absence of /-lipoprotein from serum, by immunoelectrophoresis using goat anti-human fl-lipoprotein, and by the Ouchterlony immuno-diffusion technique. Family studies revealed both parents to be heterozygous carriers.

The child has subsequently been managed on a diet

rich in medium chain triglycerides supplemented with large doses of oral vitamins A, E, and K. No further bleeding symptoms have been noted.

DISCUSSION

Abetalipoproteinemia, or Bassen-Kornzweig

syn-drome, is an uncommon autosomal recessive disease

characterized clinically by failure to thrive and fat malabsorption in infancy, with subsequent

devel-opment of spinocerebellar ataxia and retinitis

pig-mentosa.8’9 Although the disorder usually presents

in infancy or early childhood, only rarely has it

been identified prior to 3 months of age and never,

to our knowledge, with pathologic bleeding as its

first expression. The major laboratory

manifesta-tions of abetalipoproteinemia include numerous acanthocytes on the peripheral blood smear, mark-edly diminished levels of serum cholesterol and triglycerides, and absence of serum /1- lipoproteins.8

Much attention has been directed toward the

di-minished absorption of the fat-soluble vitamins A

and E rather than to vitamin K.8 A review of the

literature indicates that there are only five previous

reports (summarized in the Table) of coagulation

abnormalities in patients with

abetalipoproteine-mia.’#{176}14The prolonged prothrombin time noted in

these patients responded to vitamin K therapy but, with one exception,’#{176} was not apparently associated with hemorrhage.

Extensive coagulation tests, including factor

as-says, were not performed on our patient’s plasma.

However, the clinical and laboratory findings as

well as the prompt response to vitamin K leave

little doubt that vitamin K deficiency was

respon-sible for the hemorrhagic diathesis. Breast milk

contains little vitamin K. Thus, on rare occasions

some otherwise normal breast-fed infants between

4 and 12 weeks of age who failed to receive vitamin

K shortly after birth have been reported to develop

hemorrhage,2’4 However, a disorder of intestinal

absorption must always be suspected in this clinical

situation. The experience with our patient indicates

that abetalipoproteinemia must be added to cystic

fibrosis as a condition to be ruled out when an

infant hemorrhages after the immediate neonatal

period because of vitamin K deficiency. Therefore,

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Figure. A large ecchymosis is shown on the anterior chest wall, while pressure is being

applied to a bleeding antecubital venipuncture site.

TABLE.

Patients with Abetalipoproteinemia and Coagulation Abnormalities

162

PEDIATRICS

Vol. 65 No. 1 January

1980

Author(s) and

Reference

Age and Sex

of Patient

PT (sec)

PTT (sec)

Bleeding Signs and Symptoms

Response to Vitamin K

Sobreville et j’3 15 yr, F 15, 16, 21 . .. None Yes

Lees’2 1 yr, F 70 . - . None Yes

Ways et j’4 7 yr, M 20-24 . - . None Yes

Bach et a!’#{176} 14 mo, F

-f

- . . Ecchymoses Yes

Dische and Porro” 10 yr, M - - None ...

This report 6 wk, M 51 193 Ecchymoses, bleeding

after venipuncture

Yes

* Three separate determinations.

t Prothrombin (factor II), 13%; factor VII, 10%; factor V, 80%.

:1:“Studies indicated inadequate vitamin K absorption.”

a careful examination of the peripheral blood smear

for acanthocytes is mandatory in such patients.

Since spiculated red blood cells occur in many

disorders, including vitamin E deficiency, definitive

blood

lipid studies must then be carried out to

establish a specific diagnosis of

abetalipoproteine-mia.

REFERENCES

Department of Pediatrics

University of Texas Health Science

Center at Dallas

Dallas

ACKNOWLEDGMENTS

We wish to thank Dr Charles M. Ginsburg for provid-ing the photograph used in the figure, Dr David W. Bilheimer for performing the lipoprotein studies, Dr

Charles Mize for reviewing the manuscript, and Mrs

Dawn Miller for secretarial assistance.

FERNAN M. CABALLERO, MD

GEORGE R. BUCHANAN, MD

1. Aballi AJ: Hemorrhagic disease of the newborn. Pediatr

Ann 3:35, 1974

2. Lukens JN: Vitamin K and the older infant. Am J Dis Child

124:639, 1972

3. Goldman HI, Amadio P: Vitamin K deficiency after the

newborn period. Pediatrics 44:745, 1969

4. Nammacher MA, Willemin MT, Hartmann JR, et al:

Vi-tamin K deficiency in infants beyond the neonatal period. J

Pediatr 76:549, 1970

5. Torstenson OL, Humphrey GB, Edson JR, et a!: Cystic

fibrosis presenting with severe hemorrhage due to vitamin

K malabsorption: a report of three cases. Pediatrics 45:857,

1970

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Reprint requests to (R.G.S.) Mary Bridge Children’s Health Center, 31 1 South L Street, Tacoma, WA 98405.

PEDIATRICS (ISSN 0031 4005). Copyright © 1980 by the American Academy of Pediatrics.

EXPERIENCE

AND

REASON

163

6. Walters TR, Koch HF: Hemorrhagic diathesis and cystic

fibrosis in infancy. Am J Di.s Child 124:641, 1972

7. Oppenheimer EH, Schwartz A: Easy bruisability and

termi-nal coma in a “normal” 5-month-old infant. J Pediatr 88:

1049, 1976

8. Herbert PN, Gotto AM, Fredrickson DS: Familial

lipopro-tein deficiency (abetalipoproteinemia,

hypobetalipoprotein-emia, and Tangier disease), in Stanberry JB, et al (eds): The

Metabolic Basis of Inherited Disease, ed 4. New York, McGraw Hill Book Co, 1978, p 552

9. Bruyn GW: Bassen-Kornzweig disease, in Vinken PJ, Bruyn

GW (eds): Handbook of Neurology. Part 3: Metabolic and

Deficiency Diseases of the Central Nervous System, Vol. 29.

Amsterdam, North-Holland Publishing Co, 1977, p 401

10. Bach C, Polonovski J, Polonovski C, et al: L’absence

con-genitale de ,6-lipoproteines: une nouvelle observation. Arch

Fr Pediatr 24:1093, 1967

1 1. Dische MR, Porro RS: The cardiac lesions in

Bassen-Korn-zweig syndrome: Report of a case, with autopsy findings. Am

JMed49:568, 1970

12. Lees RS: Immunological evidence for the presence of B

protein (apoprotein of /3-lipoprotein) in normal and

abeta-lipoproteinemic plasma. J Lipid Res 8:396, 1967

13. Sobrevilla LA, Goodman ML, Kane CA: Demyelinating

cen-tral nervous system disease, macular atophy and

acantho-cytosis (Bassen-Kornzweig syndrome). Am J Med 37:821,

1964

14. Ways P0, Parmentier CM, Kayden HJ, et al: Studies on the

absorptive defect for triglyceride in abetalipoproteinemia. J

Clin Invest 46:35, 1967

Premie

Nipples:

A Potential

Aspiration

Hazard

Nipples for dispensing milk to infants are sold

throughout the United States and Canada in a

diversity of retail outlets. The nipples have been

designed in a variety of forms to include soft nipples

for premature infants. The nipples for premature

infants tend to be of thinner stock and more pliable

ing that they have been prepared for premature

infants, the adult who purchases them may not

recognize that difference when they are displayed

in an area that also provides standard nipples. The

use of nipples designed for premature infants may

present an aspiration hazard if they are used by a

full-term infant.

CASE REPORT

In January 1979, a mother brought her 18-day-old

infant in for an examination. The mother related that the

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than nipples designed for full-term infants.

Al-though the nipples may well have labeling

indicat-7-lb infant was given formula in a bottle equipped with

an Evenflo nipple (model 2937.T) that was produced by

the Pyramid Nipple Company. The mother stated that

within 90 seconds, the infant had chewed off the end of

the nipple leaving a defect 1 1 x 10 mm on the end of it (Figure). This resulted in a foreign body that measured about 10 x 1 1 x 1 mm in the baby’s mouth. Fortunately,

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1980;65;161

Pediatrics

Fernan M. Caballero and George R. Buchanan

Abetalipoproteinemia Presenting as Severe Vitamin K Deficiency

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1980;65;161

Pediatrics

Fernan M. Caballero and George R. Buchanan

Abetalipoproteinemia Presenting as Severe Vitamin K Deficiency

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