acceptability/tolerance of protein substitutes in tablet form for the dietary management of rare aminoacidopathies

Conditions: Tyrosinemia, Type I; Tyrosinemia, Type II; Tyrosinemia, Type III; Alkaptonuria; Homocystine; Metabolic Disorder; MSUD (Maple Syrup Urine Disease)

Summary: the purpose of this prospective, observational study is to evaluate the tolerability and acceptability of zero minis, a range of protein substitute tablets for use in the dietary management of children with either tyrosinaemia type i, ii, iii or alkaptonuria, homocystinuria, or maple syrup urine disease (msud) over the age of 7 years.

the principle treatment for children with inborn amino acid disorders is a strict low protein diet. part of this treatment requires the administration of a protein substitute in order to meet basic protein requirements for normal growth and development. several brands of protein substitutes for inborn amino acid disorders are already available in various presentations. however, compliance with taking protein substitutes continues to be a challenge. as a low protein diet is usually recommended for life, long term compliance is always a major concern. as a result, improving the choice in terms of product type may aid compliance. zero minis are a range of protein substitute tablets specifically designed for use in the dietary management of rare amino acid disorders like tyrosinaemia type i, ii, iii or alkaptonuria, homocystinuria, and msud in children from ≥3 years of age onwards. zero minis are concentrated protein substitutes containing a mixture of pure amino acids (except the amino acid(s) which can´t be metabolized) enriched with vitamins, minerals and trace elements. it is anticipated that they will be a suitable alternative choice for patients with rare metabolic disorders including: tyrosinaemia type i, ii, iii or alkaptonuria, homocystinuria, or msud, broadening the variety of protein substitutes they can choose from in order to suit their lifestyle and preferences. this is a prospective, multicentre, observational tolerance study with 15 children with rare metabolic disorders. subjects who are currently taking a protein substitute for the dietary management of either tyrosinaemia type i, ii, iii or alkaptonuria, homocystinuria, or msud, will be recruited for a 7-day trial taking the new ready-to-use protein substitute tablets to evaluate the tolerability and acceptability of the study products. subjects will replace some or all of their usual protein substitute with the new product suitable for their diagnosed rare metabolic disease. during the 7-day trial subjects or caregivers will be asked to complete a daily questionnaire recording information on: * usage and compliance * ease of use and any issues with administration * any gastro-intestinal side-effects. a questionnaire will also be completed at the beginning and end of the study that will consider perceptions about taste, appearance, smell, presentation and packaging of each product; ease of administration; how it is taken; and any other problems or symptoms. the amount of tablets prescribed will be calculated to provide the same amount of protein as their usual protein substitute. subjects will continue to have weekly blood tests as is routine in rare metabolic disorders. the results whilst on the study product will be compared with results whilst on their usual protein substitute. 15 children out of a patient pool with tyrosinaemia type i, ii, iii or alkaptonuria, homocystinuria, or msud will be recruited. when an appropriate subject has been identified, a study information sheet will be sent to the subject or parents/caregivers. they will be invited to request further information about the study if they wish by contacting the lead dietitian. recruitment of each patient will be by written informed consent, which will be completed by the parents/primary caregivers and taken by the lead dietitian. children will also complete an assent/consent form and will receive an information sheet, if considered appropriate for their level of understanding.

Eligibility criteria:
inclusion criteria: * diagnosis of tyrosinaemia type i, ii iii or alkaptonuria requiring a tyrosine- and phenylalanine-free protein substitute. * diagnosis of homocystinuria requiring a methionine-free, cystine-enriched protein substitute. * diagnosis of msud requiring a valine-, leucine- and isoleucine-free protein substitute. * subjects who are already taking a protein substitute for one of the specified rare metabolic disorders and are willing to try the study product for 7 days. * children aged 7 years and over. * written informed consent obtained from parental caregiver. exclusion criteria: * presence of serious concurrent illness * lead dietitian's uncertainty about the willingness or ability of the patient to comply with the protocol requirements * participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study. * any children having taken antibiotics over the previous 2 weeks leading up to the study. * children less than 7 years of age.