Pediatric Nutrition in Practice

Inborn Errors of Metabolism 229

3

olism and, as a consequence, the reversal of the

breakdown of endogenous protein [3].

Treatment strategies include: (1) natural pro-

tein restriction of precursor amino acids (aiming

to provide safe levels of protein intake [6] ); (2)

maintaining an optimal energy intake; and (3)

use of adjunctive compounds to dispose of toxic

metabolites (e.g. carnitine) or to increase activity

of deficient enzymes (e.g. vitamin B 12 in MMA).

Some inherited metabolic disease centres pre-

scribe precursor-free amino acids to supplement

natural protein intake, although the long-term

value of these supplements remains uncertain. In

MMA and PA, to reduce the production of pro-

pionate, it is also necessary to avoid prolonged

fasting (with the use of overnight tube feeding) in

order to limit oxidation of odd-chain fatty acids

liberated from triglyceride stores during lipoly-

sis. Also in MMA/PA, metronidazole is given to

reduce intestinal production of propionate. Met-

abolic decompensation caused by catabolic stress

(e.g. from vomiting and decreased oral intake) re-

quires prompt intervention with an emergency

regimen.

Urea Cycle Disorders

UCD are rare defects in waste nitrogen metabo-

lism associated with the breakdown of protein

and other nitrogen-containing molecules [7].

Partial deficiency or total absence of any of the

enzyme activities in the urea cycle (including car-

bamoyl-phosphate synthetase 1, ornithine car-

bamoyltransferase, argininosuccinate synthetase,

argininosuccinate lyase and arginase) causes ac-

cumulation of ammonia and glutamine, and nor-

mal arginine biosynthesis is interrupted. The re-

sulting hyperammonaemia and central nervous

system dysfunction is associated with high mor-

tality and morbidity. Although symptoms mainly

develop in the neonatal period, patients differ in

age at presentation, in the character and severity

Table 1 of symptoms and in their susceptibility to meta-

(continued)

Condition

Incidence

Classification

Symptoms in untreated patients

Treatment

HCU

1 in 344,000

Pyridoxine responsive

• 
  

Dislocation of the optic lens, myopia

• 
  

Classic HCU only

in classic

Non-pyridoxine responsive

and glaucoma

• 
  

Low-methionine diet (classic HCU tolerates a

HCU

• 
  

Osteoporosis, scoliosis, thinning and

median of 230 mg/day)

(varies from

lengthening of the long bones

• 
  

Methionine-free

L-amino acid supplement

1 in 65,000 to

• 
  

Learning difficulties, developmental delay,

• 
  

Cystine supplements if blood levels low

1 in 900,000)

psychiatric problems, EEG abnormalities

(dosage titrated according to blood levels)

and epilepsy

• 
  

Use of low-protein foods (special and natural) to maintain

• 
  

Thromboembolism

‘normal’ energy requirements

• 
  

Vitamin/minerals/essential and LC PUFA

• 
  

Folic acid supplementation

• 
  

Betaine supplementation

BCKD = Branched-chain α-keto acid dehydrogenase; BCAA = branched-chain amino acids; LC PUFA = long-chain polyunsaturated fatty

acids.

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