Dietary Management, Clinical Status and Outcome of Patients with Citrin Deficiency in the UK.

BACKGROUND: Little is known about the optimal dietary treatment for citrin deficiency. Our aim is to describe the management of UK citrin deficiency patients. METHODS: A longitudinal retrospective review was performed. Data were collected from medical records on presenting signs and symptoms, dietary management and clinical outcome. RESULTS: data were collected on 32 patients from 21 families. 50% were females (16/32). Median age at diagnosis was 4 y (5 days-35 y) with 12 patients diagnosed in the neonatal period with neonatal intrahepatic cholestasis (NICCD), eight later in childhood (FTTDCD) and 12 by family screening based on index cases from five families. No patient had adult-onset type II citrullinemia. The patient age at the time of data collection was a median of 11 y (1-44 y). 91% (29/32) of patients had normal physical and neurological development, 47% (15/32) experienced recurrent unexplained abdominal pain and 9% (3/32) episodes of hypoglycaemia. Siblings had different phenotypes (5 families had > 1 affected patient). Most patients preferred high protein foods, limiting sugar-containing foods. Only 41% (13/32) were prescribed a low CHO, high protein, high fat diet (restriction varied) and two used medium chain triglyceride (MCT) supplements. No patient was prescribed drug therapy. Twenty-five per cent (8/32) of patients were underweight and 41% (13/32) had height <-1 z-scores. CONCLUSIONS: patients presented with various phenotypes, symptoms and suboptimal growth. Symptoms and biochemical markers improved with age, but height remained low in some. More research is necessary to assess the effectiveness of dietary approaches in improving clinical outcomes and symptoms in citrin deficiency.

Development of national consensus statements on food labelling interpretation and protein allocation in a low phenylalanine diet for PKU.

BACKGROUND: In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients. METHODOLOGY: In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Based on majority responses, 16 statements were developed. Over 18-months, using Delphi methodology, these statements were systematically reviewed and refined with a facilitator recording discussion until a clear majority was attained for each statement. In Phase 2 and 3 a further 7 statements were added. RESULTS: The statements incorporated controversial dietary topics including: a practical 'scale' for guiding calculation of protein from food-labels; a general definition for exchange-free foods; and guidance for specific foods. Responses were divided into paediatric and adult groups. Initially, there was majority consensus (≥86%) by paediatric dietitians (n = 29) for 14 of 16 statements; a further 2 structured discussions were required for 2 statements, with a final majority consensus of 72% (n = 26/36) and 64% (n = 16/25). In adult practice, 75% of dietitians agreed with all initial statements for adult patients and 40% advocated separate maternal-PKU guidelines. In Phase 2, 5 of 6 statements were agreed by ≥76% of respondents with one statement requiring a further round of discussion resulting in 2 agreed statements with a consensus of ≥71% by dietitians in both paediatric and adult practice. In Phase 3 one statement was added to elaborate further on an initial statement, and this received 94% acceptance by respondents. Statements were endorsed by the UK National Society for PKU. CONCLUSIONS: The BIMDG dietitians group have developed consensus dietetic statements that aim to harmonise dietary advice given to patients with PKU across the UK, but monitoring of statement adherence by health professionals and patients is required.

Evaluation of an African swine fever (ASF) vaccine strategy incorporating priming with an alphavirus-expressed antigen followed by boosting with attenuated ASF virus.

In this study, an alphavirus vector platform was used to deliver replicon particles (RPs) expressing African swine fever virus (ASFV) antigens to swine. Alphavirus RPs expressing ASFV p30 (RP-30), p54 (RP-54) or pHA-72 (RP-sHA-p72) antigens were constructed and tested for expression in Vero cells and for immunogenicity in pigs. RP-30 showed the highest expression in Vero cells and was the most immunogenic in pigs, followed by RP-54 and RP-sHA-p72. Pigs primed with two doses of the RP-30 construct were then boosted with a naturally attenuated ASFV isolate, OURT88/3. Mapping of p30 identified an immunodominant region within the amino acid residues 111-130. However, the principal effect of the prime-boost was enhanced recognition of an epitope covered by the peptide sequence 61-110. The results suggest that a strategy incorporating priming with a vector-expressed antigen followed by boosting with an attenuated live virus may broaden the recognition of ASFV epitopes.