Adherence Issues in Inherited Metabolic Disorders Treated by Low Natural Protein Diets

Abstract

Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor-free or essential <smlcap>l</smlcap>-AAs are important in all these conditions. Optimal long-term outcome depends on early diagnosis and good metabolic control, but because of the rarity and severity of conditions, randomized controlled trials are scarce. In all of these disorders, it is commonly described that dietary adherence deteriorates from the age of 10 years onwards, at least in part representing the transition of responsibility from the principal caregivers to the patients. However, patients may have particular difficulties in managing the complexity of their treatment because of the impact of the condition on their neuropsychological profile. There are little data about their ability to self-manage their own diet or the success of any formal educational programs that may have been implemented. Trials conducted in non-phenylketonuria (PKU) patients are rare, and the development of specialist <smlcap>l</smlcap>-AAs for non-PKU AA disorders has usually shadowed that of PKU. There remains much work to be done in refining dietary treatments for all conditions and gaining acceptable dietary adherence and concordance, which is crucial for an optimal outcome.

The Micronutrient Status of Patients with Phenylketonuria on Dietary Treatment: An Ongoing Challenge

“…Serum concentrations of folate were frequently in excess of the RR (65% above the UTI), as previously reported [12], particularly in older children. There is emerging evidence that excessive intakes of folate may be associated with an increased risk or enhanced progression of some cancers and pre-malignant lesions [11,12,13,14,15,16,17]. As micronutrient-supplemented L -amino acids provide the majority of nutrition in a low-phenylalanine diet, it is essential that the efficacy of any change to micronutrient profiles be assessed.…”

Switch from Sodium Phenylbutyrate to Glycerol Phenylbutyrate Improved Metabolic Stability in an Adolescent with Ornithine Transcarbamylase Deficiency

“…In both years preceding start of GPB treatment, the patient required monthly hospitalizations. Although it cannot be excluded that the improvement was purely spontaneous, this is unlikely given the following considerations: patients with inherited metabolic disorders tend to become unstable during adolescence and numbers of decompensations often increase (MacDonald et al 2012). Further, the response to the change in drug treatment was rather prompt rendering a purely age-related effect unlikely.…”

Growth Hormone Deficiency and Lysinuric Protein Intolerance: Case Report and Review of the Literature

“…Several studies have demonstrated that growth response on GH treatment is positively influenced by a young age at the start of treatment (Ranke et al 2007). Moreover, optimal long-term outcome, such as stature, in inherited disorders depends on early diagnosis and good metabolic control (MaCdonald et al 2012). Our patient was treated by 7 years of age, and chronic dysmetabolism and delayed rhGH therapy could be responsible for growth impairment.…”