Januari 2012
28
If hypophosphatemic rickets and renal tubular acidosis as result of tubular dysfunction remain
notwithstanding NTBC and dietary treatment, this should be treated (with phosphate and/or
vitamin D supplementation and alkali therapy respectively).
The full impact of NTBC on kidney function is not clear yet, but tubular dysfunction tends to
decrease later than liver problems.
Neurologic crisis
The neurologic crises are acute episodes of peripheral neuropathy with an active phase dominated
by painful paresthesias, autonomic signs and sometimes progressive paralysis (which can lead to
respiratory insufficiency) and a phase of recuperation. A painful crisis is a variant, often following a
minor infection, in which the child develops excruciating pain, often in the legs. This can be
accompanied by convulsions and altered mental state.
10
During the acute phase of a neurologic
crisis analgesia and if necessary narcotics are provided. Next to the required measures for
hypertension, electrolytes imbalance and potential respiratory failure.
2
Barbiturates and other medication that can aggravate porphyria should be avoided, prior to
stabilization on NTBC.
10
Acute neurologic complications have not been reported to occur following adequate treatment
with NTBC.
10
Neurologic crisis observed in treated children have always been associated with a
prolonged interruption in NTBC treatment.
2
All patients who are not treated should be observed
closely during illnesses.
10
Developmental delay
Latest results of various countries showed that neurocognitive development can remain behind
expectations and normal individuals.
18
Therefore, this is important in follow-up and deserves
further research to look for possible causes.
Ocular abnormalities
Animal experiments have shown that long-term administration may produce corneal opacities.
Based on a case report it was suggested that blood tyrosine concentration above 600 μmol/L
confers a risk of bilateral, linear, branching subepithelial corneal opacities.
14
However a study with
11
patients with tyrosinemia type 1 on NTBC no signs of ocular toxicity or symptoms were found,
even despite high plasma tyrosine concentrations in some patients. Therefore, in absence of ocular
symptoms, frequent ophthalmic follow-up is unnecessary in patients treated with NTBC and a low-
tyrosine diet.
15
Even though there is no consistent relationship between the development of ocular symptoms and
markedly high tyrosine levels, it is recommended that photophobia in NTBC-treated patients
should lead to rapid ophthalmologic evaluation.
10
Cardiomyopathy
Cardiomyopathy was found in 30% of a study population at initial echocardiography, without any
symptoms related to the cardiovascular system. All patients showed complete resolution or
significant improvement of cardiomyopathy over time. No child with a normal initial
echocardiography subsequently developed cardiomyopathy. Cardiomyopathy was significantly less
common in those treated initially with NTBC.
16
Ultrasound is the most sensitive and specific method for the diagnosis of cardiomyopathy,
although it can also be detected by electrocardiography.
16
Children with tyrosinemie at presentation should have a cardiovascular assessment including
ultrasound. If this is normal no further investigation is necessary. If the ultrasound is abnormal, an
optimistic prognosis can be given, but further follow-up is indicated.
16