Abstract
In a longitudinal retrospective study, we aimed to assess natural protein (NP) tolerance and metabolic control in a cohort of 20 Hereditary Tyrosinaemia type I (HTI) patients. Their median age was 12 years ([3.2–17.7 years], n = 11 female, n = 8 Caucasian, n = 8 Asian origin, n = 2 Arabic and n = 2 Indian). All were on nitisinone (NTBC) with a median dose of 0.7 g/kg/day (range 0.4–1.5 g/kg/day) and were prescribed a tyrosine (Tyr)/phenylalanine (Phe)-restricted diet supplemented with Tyr/Phe-free L-amino acids. Data were collected on clinical signs at presentation, medical history, annual dietary prescriptions, and blood Phe and Tyr levels from diagnosis until transition to the adult service (aged 16–18 years) or liver transplantation (if it preceded transition). The median age of diagnosis was 2 months (range: 0 to 24 months), with n = 1 diagnosed by newborn screening, n = 3 following phenylketonuria (PKU) screening and n = 7 by sibling screening. Five patients were transplanted (median age 6.3 years), and one died due to liver cancer. The median follow-up was 10 years (3–16 years), and daily prescribed NP intake increased from a median of 5 to 24 g/day. Lifetime median blood Tyr (370 µmol/L, range 280–420 µmol/L) and Phe (50 µmol/L, 45–70 µmol/L) were maintained within the target recommended ranges. This cohort of HTI patients were able to increase the daily NP intake with age while maintaining good metabolic control. Extra NP may improve lifelong adherence to the diet.
Highlights
Hereditary Tyrosinaemia type I (HTI) is a rare inherited autosomal recessive disorder caused by reduced activity of fumarylacetoacetate hydrolase (FAH) [1], an enzyme mainly expressed in the liver and kidney
Five patients required liver transplantation, and one patient died at 3 years of age due to hepatic carcinoma
Ten patients (50%) received temporary Phe supplementation, usually in the first 2 years of life, at a median dose of 100 mg/day during the review period. This is the first longitudinal review describing lifelong changes in natural protein (NP) tolerance together with metabolic control in HTI patients treated with diet and NTBC
Summary
Hereditary Tyrosinaemia type I (HTI) is a rare inherited autosomal recessive disorder caused by reduced activity of fumarylacetoacetate hydrolase (FAH) [1], an enzyme mainly expressed in the liver and kidney. FAH is involved in the last step of tyrosine (Tyr) breakdown [2]. Its reduced activity leads to an accumulation of the toxic metabolites fumarylacetoacetate, maleylacetoacetate and their derivatives succinylacetoacetate [1,3] and increases the risk of developing hepatocellular carcinoma. The incidence of HTI in the UK is around 1 in 100,000 live births [4]. Many countries conduct newborn screening for HTI due to the availability of an effective treatment option after early diagnosis. Newborn screening is highly sensitive and specific when using
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