Inborn Errors of Metabolism 227
3
from oral glucose polymer solutions or intrave-
nous glucose) to reduce production of potentially
toxic metabolites or to prevent hypoglycaemia
[1]. This is essential for a variety of conditions in-
cluding MSUD, organic acidaemias, UCD, long-
chain and medium-chain fatty acid oxidation
disorders and GSD.
Disorders of Amino Acid Metabolism
Deficiencies in enzymes involved in amino acid
metabolism cause abnormalities in the break-
down of amino acids, resulting in the accumula-
tion of toxic substances, e.g. phenylalanine, phe-
nylpyruvate and phenylacetic acid in PKU, and
subsequent organ damage ( table 1 ) [2]. The brain,
liver and kidney are the most frequently affected
organs. Some disorders cause chronic neurologi-
cal damage without acute decompensation (e.g.
PKU), others cause acute symptoms associated
with catabolic states leading to endogenous pro-
tein breakdown and release of amino acids
(MSUD) [3]. Dietary treatment is essential for
PKU, homocystinuria (HCU), MSUD and tyro-
sinaemia type 1 (HT1) [4].
Dietary treatment involves:
- Avoidance of foods high in natural protein to
prevent excess accumulation of the ‘precursor’
amino acid(s); foods such as meat, fish, eggs,
cheese, nuts and seeds are not permitted un-
less it is a very mild disorder phenotype - A limited amount of natural protein is given to
maintain ‘precursor’ blood amino acids within
the target treatment range; natural food sourc-
es allocated for substrate amino acids are from
cereal, potato, some vegetables and milk - Provision of L -amino acids that are free of
‘precursor’ amino acids to meet at least safe
levels of protein/nitrogen requirements with
an additional amount to compensate for the
inefficiency of L -amino acid utilisation - Provision of indispensable/conditionally in-
dispensable amino acids that may become de-
ficient as a result of the enzyme block or di-
etary treatment (e.g. phenylalanine in HT1,
cystine in HCU)- Maintenance of a normal energy intake by en-
couraging the use of foods naturally low in
protein and of specially manufactured low-
protein foods such as bread and pasta - Prevention of catabolism and metabolic de-
compensation during illness/trauma, particu-
larly in MSUD
Diet may be the sole form of therapy or used
in combination with other treatments. In mild or
moderate PKU, adjunct therapy in the form of
tetrahydrobiopterin, a coenzyme in the hydrox-
ylation reaction of phenylalanine to tyrosine,
may help to enhance natural protein tolerance or
improve blood phenylalanine control. It acts as a
chaperone to increase the activity of the defective
enzyme [4]. In HT1, the drug nitisinone inhibits
the accumulation of the catabolic intermediates
which are converted to succinyl acetone and suc-
cinyl acetoacetate, which are responsible for liver
and kidney toxicity [5].
Organic AciduriasOrganic acidurias are a diverse group of disor-
ders, typically in the degradative pathways of
amino acids, carbohydrates and fatty acids, char-
acterised by increased excretion of organic acids
in the urine. They include the conditions affect-
ing abnormal catabolism of branched-chain ami-
no acids: methylmalonic aciduria (MMA), pro-
pionic aciduria (PA) and isovaleric aciduria
( table 2 ). Clinical features frequently include en-
cephalopathy and episodic metabolic acidosis,
caused not only by the accumulation of toxic in-
termediates but also by disturbances of mito-
chondrial energy metabolism and carnitine ho-
moeostasis [3]. Symptoms commonly develop
between days 2 and 5 of life, although they can
commence at any age. Major goals of therapy are
the reversal of catabolism, the promotion of anab-Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 226–233
DOI: 10.1159/000360344