Pediatric Nutrition in Practice

Inborn Errors of Metabolism 231

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bolic derangement depending on the affected en-
zyme and its residual activity [8].
Treatment for UCD involves reducing protein
intake, supplementing essential amino acids and
avoiding catabolic states. Drug therapy produces
alternative pathways for nitrogen excretion and
includes ammonia-scavenging drugs (e.g. sodi-
um phenylbutyrate or sodium benzoate) and ar-
ginine (except in arginase deficiency), which pro-
motes incorporation of ammonia into citrulline
and arginosuccinate. L -Citrulline may be given
a s a n a lter nat ive to a rg i n i ne i n or n it h i ne c a rba m-
oyltransferase and carbamoyl-phosphate syn-
thase deficiency [7].

Disorders of Fatty Acid Oxidation

Mitochondrial fatty acid oxidation is required
for energy during fasting, either through com-
plete oxidation or through production of ke-
tones in the liver that then serve as an alternative
energy source for the brain. Disorders are main-
ly precipitated by fasting and typically present as
hypoketotic hypoglycaemia, which leads to
coma or convulsions. The most common fatty
acid disorder in Northern Europe is medium-
chain acyl-CoA dehydrogenase deficiency
(MCADD) [5]. In unscreened populations,
MCADD is associated with 25% mortality on
presentation. Most children identified through
newborn screening remain well without long-
term sequelae. Precipitating factors of acute
metabolic episodes in infancy include prolonged
fasting caused by vomiting/diarrhoea/fever, and
in teenagers/adults strenuous exercise, alcohol
and drugs (with vomiting/fasting), surgery and
pregnancy [9]. Treatment consists of avoidance
of fasting and use of an emergency regimen with
illness/surgery/trauma. See table 3 for suggested
safe fasting times.

Disorders of Carbohydrate Metabolism

The disorders of carbohydrate metabolism dis-

play a wide range of clinical features: symptoms

caused by toxicity (galactosaemia and hereditary

fructose intolerance, HFI) or hypoglycaemia

(GSD).

Disorders of Galactose and Fructose Metabolism

Galactosaemia is a disorder of galactose metabo-

lism causing abnormal glycosylation of glycopro-

teins and glycolipids [10]. In HFI, accumulation

of fructose 1-phosphate causes inhibition of gly-

cogen breakdown and glucose synthesis, thereby

causing severe hypoglycaemia following fructose

ingestion [11]. Both conditions are potentially

life threatening on presentation. Children with

galactosaemia and HFI typically develop evi-

dence of severe damage to the liver and kidneys

after dietary intake of lactose (milk, milk prod-

ucts) in galactosaemia or of fructose (fruits, su-

crose) in HFI [5]. Treatment includes the elimi-

nation of the intake of galactose or fructose, re-

spectively. In HFI, an aversion to fructose is

common.

Children with galactosaemia often present in

the first week of life. Children with HFI develop

symptoms after the introduction of fruits, vege-

tables and particularly table sugar (the fructose-

glucose disaccharide sucrose) to their diet, often

between 4 and 8 months of age [1 2]. Long-term

complications are common in galactosaemia and

appear to be independent of the severity of ill-

ness, type of diet therapy or dietary adherence,

and there is debate about how stringent dietary

restriction should be later in life. In contrast, in

HFI outcome is good, with normal growth, intel-

ligence and life span [1 2].

Disorders of Gluconeogenesis and Glycogen

Storage

GSD are defects of a number of different en-

zymes involved in glycogen synthesis and degra-

dation [13]. Glycogen is primarily stored in the

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