Neonatal hyperammonemia caused
a defect of carnitine-acylcarnitine
translocase
by
H. Ogier de Baulny, MD, A. Slama, PhD, G. Touati, MD, D. M. Turnbull, MD,
M. Pourfarzam, Phb, and M. Brivet, PhD
From the Centre d'investigation ctinique, H6pital Robert Debr6, Paris, France, the Depart-
ment of Clinical Neuroscience and Child Health, The Medical School, Newcastle upon Tyne,
United Kingdom, and the Laboratoire central de biochimie, centre hospitalier de Bic6tre,
Le Kremlin Bic6tre, France
Carnitine-acylcarnitine translocase deficiency is a newly recognized inborn error
of metabolism that involves transport of long-chain fatty acids into mitochondria,
which in turn impairs mitochondrial 13-oxidation, and ketogenesis. We report a
new familial example; the affected twins had neonatal distress, hyperammone-
mia, and transient intracardiac conduction defects.Clinical and biochemical
analysis of both our patients and the two previously reported patients revealed
that this inherited defect could be manifested during the neonatal period without
any of the signs classically associated with fatty oxidation defects. In contrast, all
four patients had sustained and "isolated" hyperammonemia, which could be
misinterpreted as being caused by urea cycle defects. We conclude that
carnitine-acylcarnitine translocase deficiency is a potential differential diagnosis
in neonates with unexplained neonatal hyperammonemia. Cardiac and muscle
involvement may represent further early pivotal symptoms. (J PEDIATR 1995;
127:723-8)
Apart from the urea cycle disorders, a number of other in-
born errors of metabolism, including organic acidurias, some
congenital lactic acidemias, and defects in fatty acid oxida-
tion, can cause hyperammonemia.1 In addition, transient hy-
perammonemia in the neonate is a condition of unknown
origin in which the diagnosis relies on the exclusion of the
conditions noted above. The fatty acid oxidation defects are
characterized by acidosis, hypoglycemia, and dicarboxylic
aciduria, but none of these biochemical markers is a constant
finding, and neonatal fatty acid oxidation defects may easily
be misdiagnosed in the absence of a high level of suspicion. 2
We describe premature twins who had a long-chain fatty
Supported in part by a grant from' 'recherche clihique' ' No. 930 608
and by Action Research for the Crippled Child.
Reprint requests: Hrl~ne Ogier de Baulny, Centre d'investigation
clihiqne, Hrpital Robert Debrr, 48 Boulevard Serurier, 75019 Paris,
France.
Submitted for publication Feb. 28, 1995; accepted Jtme 9, 1995.
Copyright © 1995 by Mosby-Year Book, Inc.
0022-3476/95/$5.00 + 0 9/20/66928
oxidation defect caused by carnitine-acylcarnitine translo-
case deficiency, with neonatal "isolated" hyperammonemia
as the initial manifestation.
CASE REPORT
These twins, the first children of Algerian consanguineous par-
ents, were born at 34 weeks of gestation with birth weights of
2050 and 2300 gm, respectively. Along with intravenous glucose
CoA Coenzyme A
CPT Camitine palmityl transferase
MCT Medium-chain triglyceride
NAGA N-Acetylglutamate [synthetase]
infusions and antibiotics, continuous nasogastric feeding with a
medium-chain triglyceride-supplemented formula was started
within the first 24 hours of life. Both had neurologic examination
appropriate for gestational age, and blood glucose levels were nor-
mal on repeated testing.
On the second day of life, twin A, a girl, had unexplained recur-
rent episodes of tachypnea, cyanosis, and bradycardia. At 72 hours
of life, abrupt deterioration with tracheal hemorrhage required
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