A new study published in Orphanet Journal of Rare Diseases indicates patients with hereditary tyrosinemia type 1 (HT-1) may be at greater risk for intellectual disabilities.
The study by van Ginkel et al tested 19 children with HT-1 and found they had lower IQ scores when compared to age-matched controls.
Hereditary Tyrosinemia type 1 (HT-1)
HT-1 is a rare metabolic disorder caused by a defect in the enzyme Fumarylacetoacetate Hydrolase. Current treatment includes 2-(2-nitro-4-trifluoromethylbenoyl)-1,3-cyclohexanedione (Orfadin) and a very restrictive diet. Prior to this treatment, most children had to undergo a liver transplant to treat the condition.
Despite the success of a strict diet plus SOBI’s Orfadin to manage the condition, there has been indications that HT-1 patients have some intellectual disabilities. To further assess this, van Ginkel et al tested 19 Orfadin and dietary treated HT-1 patients (5 females, 14 males; mean age 12.9 ± 4.8 years; range 7.9–23.6 years). No liver transplant patients were included in the study. Of the 19 patients, 18 were given Orfadin and a restricted diet soon after diagnosis. One patient was diagnosed before Orfadin was available and started Orfadin treatment 2 years of dietary treatment alone.
The figure below shows estimated IQ scores. The median estimated IQ score in HT-1 patients was 85 (range: 55–111), with 2 patients having an estimated IQ between 55 and 65, 1 patient between 65 and 75, and 3 patients between 75 and 85. All other patients had IQ scores within the normal range of 85–115. Estimated IQ scores of the healthy controls were mostly within the normal range, with 4 estimated IQ scores above 115. HT-1 patients had significantly lower estimated IQ than healthy controls (U =60, P < .001).
Further analysis showed that HT-1 patients tended to have suboptimal outcome on executive functioning (working memory and cognitive flexibility) and social cognition (face recognition and the identification of facial emotions).
The researchers concluded that “HT-1 patients on average underperformed on the neurocognitive tasks compared to healthy controls when examining IQ, EF, and social cognition. The pathophysiological mechanisms that result in this brain dysfunction are not fully understood yet. Clearly, possible similarities between HT-1 and other single amino acid disorders such as PKU could help to elucidate these mechanisms.”
Van Ginkel WG, Jahja R, Huijbregts SC, et al. Neurocognitive outcome in tyrosinemia type 1 patients compared to healthy controls. Orphanet J Rare Dis. 2016; 11: 87. DOI: 10.1186/s13023-016-0472-5