Abstract
In a retrospective review, we aimed to assess long-term growth in 17 patients (n = 11 males) with hereditary tyrosinaemia type I (HTI). Median age at assessment was 15.6 years (5.7–26.6 years) and median age at diagnosis was 1 month (range: 0–16 months), with 35% (n = 6/17) symptomatic on presentation. From the age of 8 years, there was a noticeable change in median height, weight, and body-mass-index [BMI]-z-scores. Median height-for-age z-scores were consistently ≤ −1 (IQR −1.6, −0.5) during the first 8 years of life but increased with age. Weight-for-age z-scores ranged between −1 to 0 (IQR −1.2, 0.1) in the first 8 years; then increased to > 0.5 (IQR −0.3, 1.3) by age 16 years, and BMI-for-age z-scores ranged from 0 to 1 (IQR −0.7, 1.3) up to 8 years, and >1 (IQR −0.2, 1.9) until 16 years. The percentage of overweight and obesity was lowest in children aged < 5 years, and consistently > 40% in patients aged between 7 to 16 years. The prescribed total protein intake was associated with improved height growth (p < 0.01). Impaired growth in early life improved with age achieving normal population standards. Further studies are needed to investigate factors that influence growth outcome in HTI patients.
Highlights
Following the successful treatment of hereditary tyrosinaemia type I (HTI) with nitisinone (2-(2-nitro-4-trifluoromethyl-benzoyl)-1,3-cyclohexanedione, NTBC) [1,2,3], and a low phenylalanine/tyrosine diet, the management of HTI has radically altered, with a significant decrease in the number of patients needing lifesaving liver transplantations [1,2,4]
The two key observations from this longitudinal retrospective review on growth in HT1 in children treated with NTBC and a low tyrosine diet were: (1) impaired growth in early childhood associated with a negative height and weight z-score, and (2) a statistically significant correlation between height and prescribed total protein intake
The results of our study indicated that overweight and obesity rates were higher than the UK general population [28] which show that 28% of healthy children aged 2 to 15 years were overweight or obese
Summary
Following the successful treatment of hereditary tyrosinaemia type I (HTI) with nitisinone (2-(2-nitro-4-trifluoromethyl-benzoyl)-1,3-cyclohexanedione, NTBC) [1,2,3], and a low phenylalanine/tyrosine diet, the management of HTI has radically altered, with a significant decrease in the number of patients needing lifesaving liver transplantations [1,2,4]. The dietary treatment for HTI shares similar principles with other amino acid disorders. It consists of a low protein diet supplemented with a low or free tyrosine/phenylalanine protein substitute usually supplemented with vitamins, minerals, and trace elements to meet nutritional requirements. There are no agreed guidelines on blood tyrosine and phenylalanine concentrations for HTI, tyrosine is commonly maintained between 200-400 μmol/L and phenylalanine > 30 μmol/L and ideally ≥ 50 [1,13,14,15]. In HTI, low blood phenylalanine concentrations are a common finding, in the early years of life and phenylalanine supplementation is necessary [13,15,16,17]. In a phenylketonuria (PKU) animal study, pharmacological inhibition of tyrosine metabolism with NTBC increased blood and brain tyrosine, and lowered phenylalanine concentrations, suggesting that NTBC may decrease phenylalanine concentrations [18]
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