228 MacDonald^
Condition
Incidence
Classification
Symptoms in untreated patients
Treatment
PKU
Varies
Classic
or
severe
PKU
Severe intellectual and neurological impairment
Low phenylalanine diet (classic PKU, children:
between
Plasma phenylalanine
Mousy odour
tolerate 200
-^ 500 mg daily)
populations:
concentrations >1,200 μmol/l
Infantile spasms
Phenylalanine-free
L-amino acid supplement
1 in 4,000 to
Moderate
PKU
Lightly pigmented (hair, eyes and skin)
Tyrosine supplementations (usually already
1 in 200,000
Plasma phenylalanine
Eczema
added to
L-amino acid supplement)
concentrations >600
-^ 1,200 μmol/l
Microcephaly
Vitamins/minerals/essential and LC PUFA
Mild
PKU
or
hyperphenylalaninaemia
Delayed speech development
Use of low-protein foods (special and natural)
Phenylalanine concentrations
Older
patients
to maintain ‘normal’ energy requirements
<600 μmol/l
Hyperactivity
Patients with mild/moderate PKU may
Disturbed behaviour
respond to 5
-^ 20 mg/kg sapropterin daily
Austistic features
Self-injury
Abnormalities of gait
Tremor
Grand mal seizures
MSUD
1 in 116,000
Classic MSUD
Classic
(neonatal
onset)
Diet low in BCAA (leucine, valine, isoleucine;
Intermediate form
Poor feeding
‘classic’ children with MSUD tolerate 400
-^ 600 mg daily)
Intermittent form
Sweet, malty, caramel-like smell
BCAA-free
L-amino acid supplement
Thiamin-responsive form
Episodic vomiting
Valine/isoleucine supplements if blood levels low
(a cofactor for BCKD complex)
Irritability
(dosage titrated to valine/isoleucine
Hypoglycaemia
blood concentrations)
Lethargy
Vitamin/minerals/essential and LC PUFA
Encephalopathy
Use of low-protein foods (special and natural)
Cerebral oedema
to maintain ‘normal’ energy requirements
Seizures
Requires emergency regimen during illness,
Delay in diagnosis may result in
fasting, infection or surgery
neurological damage or death
Intermediate
form
Presents at any age (infancy to adulthood)
Failure to thrive
Hypotonia
Progressive developmental delay
Ketoacidosis
Intermittent
form
Episodic ataxia and ketoacidosis (often withintercurrent illness or increased protein intake)
HT1
1 in 100,000
Acute or chronic form
Acute
Diet low in tyrosine and phenylalanine
Early infancy
May tolerate up to 0.5 g/kg natural protein daily, but
Severe liver failure
amount to be titrated to tyrosine/phenylalanine
Cirrhosis
concentrations
Hepatocellular carcinoma
Tyrosine/phenylalanine-free amino acid supplement
Renal Fanconi syndrome
Phenylalanine supplements if blood levels low
Glomerulosclerosis
(dosage titrated according to blood levels)
Vitamin D-resistant rickets
Use of low-protein foods (special and natural) to
Neurological crisis
maintain ‘normal’ energy requirements
Chronic
Vitamin/minerals/essential and LC PUFA
Slight enlargement of liver
Nitisinone (1 mg/kg/day)
Mild growth retardation
Renal tubular dysfunction and rickets
Hepatosplenomegaly
Liver cirrhosis
Hepatocellular carcinoma
Table 1.
Incidence, classification and symptoms of amino acid disorders
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