Volume 82
Number 3
by the infected infants should produce a low
rather than a high KG rate.
T h e glycogen reserve and its availability
were examined by the intravenous glucagon
test. The results were comparable in the infected and in the healthy infants (Fig. 1).
It thus appears that increased peripheral
utilization is an important mechanism in the
rapid disappearance of glucose in neonatal
sepsis.
Failure to demonstrate plasma hyperinsulinism in the infected infants (Table I I I )
and significant reduction of the KG rate after
controlling the infections in them (Table I I :
Cases 3, 5, 9, 10, 11, and 13) suggest that
the increased peripheral utilization could be
the result of enhanced insulin sensitivity or
increased insulin-like activities during sepsis.
These activities probably account for the frequent occurrence of hypoglycemia in neonatal sepsis.
We are grateful to Dr. Rose Young of the
University Medical Unit, Queen Mary Hospital,
for assaying the plasma insulin levels in our infants, and the Director of Medical and Health
Services for permitting us to publish.
Normal development in an
infant of a mother with
phenylketonuria
A. Deborah Goldstein, M.D., Victor H.
Auerbaeh, Ph.D., and Warren D.
Grover, M.D., Philadelphia, Pa.
From St. Christopher's Hospital [or Children,
and the Departments o] Pediatrics, Neurology,
and Biochemistry, Temple University School o[
Nursing.
Supported in part by grants [rom the National
Institutes o[ Health General Research Support
Grant RR-5624, Clinical Research Center Grant
RR-75, and [rom the Children's Bureau
CB-416. The phenylketonuria program is
supported by the Pennsylvania Department o]
Health.
Reprint address: Warren D. Grover, M.D., St.
Christopher's Hospital [or Children, 2603N. Filth St.,
Philadelphia, Pa. 19133.
Brie[ clinical and laboratory observations
4 89
REFERENCES
1. Yeung, C. Y.: Hypoglycemia in neonatal sepsis,
J. P~DtATR. 77: 812, 1970.
2. Amatuzio, D. S., Stutzman, F. L., Vanderbilt,
M. J., and Nesbitt, S.: Interpretation of the
rapid intravenous glucose tolerance test in normal individuals and in mild diabetes mellitus,
J. Clin. Invest. 32: 428, 1953.
3. The modified method of Asatoor and King, in
Varley, H., editor: Practical clinical biochemistry, ed. 3, New York, 1964, Interscience
Publishers, Inc.
4. Cornblath, M., and Schwartz, R.: Disorders
of carbohydrate metabolism in infancy, Philadelphia, 1966, W. B. Saunders Company, p. 38.
5. LaNoue, K. F., Mason, A. D., Jr., and Daniels,
J. P.: The impairment of gluconeogenesis by
gram-negatlve infection, Metabolism 17: 606,
1968.
6. Shands, J. W., Jr., Miller, V., and Martin, H.:
The hypoglycemic activity of endotoxin. I.
Occurrence in animals hyperreactive to endotoxin, Proc. Soc. Exp. Biol. Med. 130: 413,
1969.
7. Smith, C. A.: The physiology of the newborn
infant, ed. 3, Oxford, 1959, Blaekwetl Scientific
Publications.
8. Widdowson, E. M.: Metabolic effects of fasting
and food, in Wolstenholme, G. E. W., and
O'Connor, M., editors: Ciba symposium on
somatic stability in the newly born, London,
1961, J. & A. ChurchiII, Ltd., p. 39.
A R E C E N T review records only 11 instances of phenylketonuria in the Negro race?
We report here a case of untreated classical
phenylketonuria in a Negro woman of average intelligence, whose infant had transient
hyperphenylalaninemia until six months of age
and who has had normal development up to
the present at 13 months of age. There have
been reports of Caucasian mothers with
classical phenylketonuria who have had retarded infants without phenylketonuria, 4 but
we could not find a description of the status
of infants of similarly affected mothers in the
Negro race.
CASE REPORT
The propositus, N. P. (S.C.H.C. No. 71-00160), a Negro male infant, was referred to St.
Christopher's Hospital for Children for evaluation
of elevated levels of serum phenylalanine. Serum
phenylalanine levels determined b y the Guthrie
490
Brief clinical and laboratory observations
T a b l e I. Serum phenylalanine levels
(rag./100 ml.)
Time interval
(hr.)
Propositus
]
Mother
Fasting
V~
1
2
3
4
6
8
12
1.7
1.8
3.6
1.8
-6.9
3.8
3.8
4.0
19.8
31.5
58.0
66.0
56.0
47.0
46.0
22.0
33.0
method were 6 mg. per 100 ml. at five and twenty
days of age, respectively. At the time of our
initial examination, the propositus was three
months of age, chubby, green eyed, light skinned,
and smiling. There was no unusual odor about
him and he did not have any dermal lesions.
Head circumference was 38.5 cm. (tenth percentile), length was 59 cm. (fiftieth percentile), and
weight was 6.2 Kg. (seventy-fifth percentile).
Neurologic evaluation demonstrated no abnormalities of cranial nerve functions, postural reflexes, or deep tendon reflexes. Developmental
performance at three months of age was within
normal limits.
Specimens were obtained at random from the
propositus and his parents for the determination
of serum concentrations of phenylalanine and
tyrosine, and of urinary metabolites of phenylalanine metabolism. No abnormal values were
noted in specimens obtained from the father.
The propositus demonstrated mild hyperphenylalaninemia without significant urinary excretion
of phenylpyruvic acid. The mother had a serum
phenylalanine level of 23 mg. per 100 ml.
(McCamon-Robbins method) and a urinary
phenylpyruvic acid value of 54 mg. per 100 ml.
(enol-borate method). The propositus and his
mother were given 700 mg. (100 mg. per kilogram) and 6.0 Gin. of phenylalanine, respectively,
by mouth to determine their ability to metabolize
this amino acid. The results (Table I) document
classical phenylketonuria in the mother and normal phenylalanine values in the propositus which
do not differentiate between normal metabolism
and the heterozygous state.
A psychometric evaluation of the mother, age
35 years, indicated a full-scale I.Q. of 85, judged
to be within normal limitsY The growth and
development of the propositus were judged to be
The Journal o[ Pediatrics
March 1973
within normal limits at subsequent visits: Head
circumference, weight, and length remained at
the same percentile levels. Formal developmental
testing at 13 months of age revealed a performance within normal limits. Serum phenylalanine
levels after three months of age have been in the
range of 2 to 4 mg. per 100 ml. (Guthrie inhibition assay).
Although the propositus, his mother, and materual grandmother are light skinned, green eyed,
and freckled, the family history provides no indication of Caucasian, Indian, or other ethnic
admixture. The mother has a 13-year-old daughter by a previous marriage, who is said to be
functioning adequately at the appropriate grade
level in public school; we have no psychometric
data on this child. Her serum phenylalanine level
and that of the maternal grandmother are 2.2
and 2.5 mg. per 100 ml., respectively; these concentrations suggest the carrier state.
The ethnic distribution of genes causing
phenylketonuria has been clarified by a mass
screening program. Our clinical experience with
phenylketonuria is consistent with data indicating
a low frequency in Negroes of genes for defective
phenylalanine metabolism. Of 160 patients with
classical or atypical phenylketonuria and hyperphenylalaninemia registered in our clinic, only
five are Negro patients; two have classical
phenylketonuria. In addition to the propositus,
we have, within a 5 year period, identified two
other Negro patients with other forms of hyperphenylalaninemia.
It has been postulated that in the fetuses of
mothers with classical phenylketonuria the metabolites of maternal phenylalanlne metabolism,
particularly phenylpyruvic acid, might be responsible for cerebral dysgenesis and microcephaly.a Microcephaly was not noted in this case.
There are several reports of Caucasian children
whose development was normal following birth
to a mother with classical phenylketonuria.4 The
case reported here demonstrates normal development up to 13 months of age in an infant born
to a Negro mother with classical phenylketonuria.
Further testing at an older age will be necessary
to determine future development of cognitive
skills.
The psychometric evaluation was performed
by Ira Steisel, Ph.D.
REFERENCES
1. Knox, W. E.: Phenylketonuria, in Stanbury,
J. B., Wyngaarden, J. B., and Fredrickson,
Volume 82
Number 3
Brief clinical and laboratory observations
D. S., editors: The metabolic basis of inherited
disease, ed. 3, New York, 1972, McGraw-Hill
Book Company, Inc., p. 267.
2. Jensen, A. R.: Environment, heredity, and intelligence, Reprint Series No. 2, Cambridge,
Mass., 1969, Harvard Educational Review, p.
81.
3. Auerbaeh, V. H., DiGeorge, A. M., and Carpenter, G. G.: Phenylalaninemia, in Nyhan,
Functioning solitary
nodule o/ the thyroid in
a child
A r l a n L. Rosenbloom, M.D.,
Gainesville, Fla.
S OL IT ARY
functioning
nodule of
the thy-
roid,
suppressible hy endogenous thyroid hormone, is rarely encountered at any age. 1-3 I
have not been able to find any r e p o r t of this
condition in children. I n 20 years' experience at the Johns Hopkins Pediatric E n d o crine Service, 4 only two patients with aden o m a of the thyroid were f o u n d ; no information is given on autonomy. This report describes a solitary thyroid nodule in a euthyroid 9-year-old girl, detected as a n incidental
finding, a n d functioning as her thyroid-stimulating h o r m o n e - d e p e n d e n t source of thyroid
hormone.
CASE REPORTS
The patient was admitted to the Shands
Teaching Hospital of the University of Florida
in January, 1972, at age 9~2 years, for repair
From the Division of Genetics, Endocrinology,
and Metabolism, Department of Pediatrics,
University of Florida College of Medicine
Supported in part by Developmental Physiology
Training Grant, N I H T1-HDO054, National
Institutes of Health Training Grant 1 TOI
AM05680-01 DM, National Institutes of
Health Research Grant 5 M01 RR-00082-10,
and aided by a grant from the National
Foundation-March of Dimes.
Reprint address: Department o~ Pediatrics, College o[
Medicine, University of Florida, Gainesville, Fla. 32601.
49 1
W. L., editor: Amino acid metabolism and
genetic variation, New York, 1967, McGrawHill Book Company, Inc., p. 20.
4. Frankenburg, W. K., Duncan, B. R., Coffelt,
R. W., Koch, R., Coldwell, J. G., and Son,
C. D.: Maternal phenylketonuria: Implications
for growth and development, J. P~I~IATR. 73:
560, 1968.
of an atrial septal defect. She had never had
symptoms of cardiac dysfunction, and her development and growth were normal. The murmur was initially noted at age 3 years, and at
age 6 she had undergone cardiac catheterization
elsewhere. Angiocardiography confirmed that she
had an ostiurn secundum defect, which was
repaired on January 20, 1972. Height and weight
were at the fiftieth percentile for age (Boston
standards). She had never experienced temperature intolerance, tremor, palpitation, behavioral
change, sleep disturbances, or other symptoms
of thyroid dysfunction.
On examination prior to surgery, a 6 e.c.
(3 • 2 cm.) nodule was felt over the left lobe
of the thyroid. It was soft and nontender.
There were no regional lymph nodes. Extranodular thyroid tissue was not palpable. Skin
temperature and texture were normal, there was
no tremor, reflexes were normal, and pulse rate
was 96 preoperatively and 68 to 75 postoperatively. Blood pressure was 94/64 ram. Hg.
Serum thyroxin iodine by competitive proteinbinding assey was 5.7 #g per 100 ml. seven days
after cardiac bypass surgery. 99mTechnetium
technetate scan demonstrated total thyroid uptake to be in the nodule. Following four weeks
of treatment with dessicated thyroid, 90 rag.
daily, the nodule became small and indistinct.
Repeat scan showed slight uptake in this area.
She was then given thyroid-stimulating hormone
(TSH), 10 I.U. daily intramuscularly for 3
days. The nodule returned and was firmer and
slightly larger. The technetium scan was identical to that prior to administration of thyroid
with no evidence of functioning thyroid tissue
elsewhere other than in the nodule. The dose
of thyroid was increased to 120 mg. daily. Four
months later no thyroid tissue was palpal~le, and
a scan failed to demonstrate any uptake in the
thyroid region. There were no signs or symptoms
of hyperthyroidism with this dose of thyroid
hormone.