The answer to the blog post title: mild impaired cognitive function, according to a recent study (J Pediatr 2014; 164; 398-401).

Using a cross-sectional study, children (n=10) with tyrosinemia type 1 were compared with their unaffected siblings.  Intelligence was measured with Wechsler Scales. These children were treated with nitisinone (NTBC).  NTBC which was introduced in 1992 has markedly improved the survival of tyrosinemia by blocking the accumulation of toxic metabolites.  Liver dysfunction is controlled in >90% and the risk of liver cancer has been reduced as well.

Key results:

• Average IQ score in tyrosinemia patients was lower than their siblings: 71 vs. 91 (P= .008).
• In the five patients with repeated measurements, there was a gradual decline in IQ over time (240 months), from 96 to 69.

Why?

The authors do not know but speculate that cognitive impairment may have been overlooked previously due to the short life span of untreated patients.  While the lower IQ may be due to the treatment itself, “similarly low IQs in patients who stopped taking nitisone after undergoing liver transplantation argues against the acute toxicity of nitisinone.” Thus, elevated tyrosine/low phenylalanine levels, which occurs in patients on NTBC/restricted protein diet, may be related to cognitive impairment.