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.

Uniformity of Food Protein Interpretation Amongst Dietitians for Patients with Phenylketonuria (PKU): 2020 UK National Consensus Statements.

In phenylketonuria (PKU), variable dietary advice provided by health professionals and social media leads to uncertainty for patients/caregivers reliant on accurate, evidence based dietary information. Over four years, 112 consensus statements concerning the allocation of foods in a low phenylalanine diet for PKU were developed by the British Inherited Metabolic Disease Dietitians Group (BIMDG-DG) from 34 PKU treatment centres, utilising 10 rounds of Delphi consultation to gain a majority (≥75%) decision. A mean of 29 UK dietitians (range: 18-40) and 18 treatment centres (range: 13-23) contributed in each round. Statements encompassed all foods/food groups divided into four categories based on defined protein/phenylalanine content: (1) foods high in protein/phenylalanine (best avoided); (2) foods allowed without restriction including fruit/vegetables containing phenylalanine ≤75 mg/100 g and most foods containing protein ≤0.5 g/100 g; (3) foods that should be calculated/weighed as an exchange food if they contain protein exchange ingredients (categorized into foods with a protein content of: >0.1 g/100 g (milk/plant milks only), >0.5 g/100 g (bread/pasta/cereal/flours), >1 g/100 g (cook-in/table-top sauces/dressings), >1.5 g/100 g (soya sauces)); and (4) fruit/vegetables containing phenylalanine >75 mg/100 g allocated as part of the protein/phenylalanine exchange system. These statements have been endorsed and translated into practical dietary management advice by the medical advisory dietitians for the National Society for PKU (NSPKU).

Nutritional and Metabolic Characteristics of UK Adult Phenylketonuria Patients with Varying Dietary Adherence.

The nutritional and metabolic characteristics of adult phenylketonuria (PKU) patients in the UK with varying dietary adherence is unknown. In other countries, nutritional and metabolic abnormalities have been reported in nonadherent patients compared to adherent counterparts. A pooled analysis of primary baseline data from two UK multi-centre studies was therefore performed to establish whether this is true from a UK perspective. Adult PKU patients who had provided 3-day food records and amino acid blood samples were included and grouped according to dietary adherence (adherent; n = 16 vs. nonadherent; n = 14). Nonadherent patients consumed greater amounts of natural protein compared to adherent patients (61.6 ± 30.7 vs. 18.3 ± 7.7 g/day; q < 0.001). In contrast, the contribution of protein substitutes to total protein intake was lower in nonadherent compared to adherent patients (3.9 ± 9.2 g/day vs. 58.6 ± 10.2 g/day; q < 0.001). Intakes of iron, zinc, vitamin D3, magnesium, calcium, selenium, iodine, vitamin C, vitamin A and copper were significantly lower in nonadherent compared to adherent patients and were below UK Reference Nutrient Intakes. Similarly, intakes of thiamin, riboflavin, niacin, vitamin B6 and phosphorus were significantly lower in nonadherent compared to adherent patients but met the UK Reference Nutrient Intakes. Phenylalanine concentrations in nonadherent patients were significantly higher than adherent patients (861 ± 348 vs. 464 ± 196 µmol/L; q=0.040) and fell outside of European treatment target ranges. This study shows the nutritional and metabolic consequences of deviation from phenylalanine restriction and intake of PKU protein substitutes in nonadherent adult PKU patients. Collectively, these data further underlie the importance of life-long adherence to the PKU diet.

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.

Each baby counts: National quality improvement programme to reduce intrapartum-related deaths and brain injuries in term babies.

Although the most recent MBRRACE-UK (Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK) perinatal mortality report has shown a downward trend in perinatal mortality, the UK still lags behind the best-performing countries in Europe. The burden of perinatal morbidity and mortality is wide-reaching and devastating for the families and care-providers involved. The aim of the Each Baby Counts (EBC) project is to reduce intrapartum term stillbirths, early neonatal deaths, and severe brain injuries by 50% by 2020. Every maternity care provider has been asked to report their intrapartum term stillbirths, early neonatal deaths and severe brain injuries to the EBC project and provide a copy of the local review. The local reviews are assessed by two trained EBC reviewers in order to establish whether the reviews are of adequate quality. The EBC reviewers are asked independently to assess whether there is sufficient clinical information to make a clinical judgement about care, and whether different care could have had a positive impact on the outcome. The reviewers are asked to indicate in what areas care might be improved. The analysis of the local reports will be twofold. Initially quantitative analysis will provide us with information about the scale of the problem, the quality of the local review process into adverse events, and who is involved in such reviews. Qualitative analysis of the themes highlighted in the reviews will enable us to develop care bundles or other tools to drive local quality improvement.

Effectiveness of nonpharmacologic treatments for acute seasonal allergic conjunctivitis.

OBJECTIVE: To investigate whether artificial tears and cold compress alone or in combination provide a treatment benefit and whether they were as effective as or could enhance topical antiallergic medication. DESIGN: Randomized, masked clinical trial. PARTICIPANTS: Eighteen subjects (mean age, 29.5±11.0 years) allergic to grass pollen. INTERVENTION: Controlled exposure to grass pollen using an environmental chamber to stimulate an ocular allergic reaction followed by application of artificial tears (ATs), 5 minutes of cold compress (CC), ATs combined with CC, or no treatment applied at each separate visit in random order. A subset of 11 subjects also had epinastine hydrochloride (EH) applied alone and combined with CC in random order or instillation of a volume-matched saline control. MAIN OUTCOME MEASURES: Bulbar conjunctival hyperemia, ocular surface temperature, and ocular symptoms repeated before and every 10 minutes after treatment for 1 hour. RESULTS: Bulbar conjunctival hyperemia and ocular symptoms decreased and temperature recovered to baseline faster with nonpharmaceutical treatments compared with no treatment (P <0.05). Artificial tears combined with CC reduced hyperemia more than other treatments (P <0.05). The treatment effect of EH was enhanced by combining it with a CC (P <0.001). Cold compress combined with ATs or EH lowered the antigen-raised ocular surface temperature to less than the pre-exposure baseline. Artificial tear instillation alone or CC combined with ATs or EH significantly reduced the temperature (P <0.05). Cold compress combined with ATs or EH had a similar cooling effect (P >0.05). At all measurement intervals, symptoms were reduced for both EH and EH combined with CC than CC or ATs alone or in combination (P <0.014). CONCLUSIONS: After controlled exposure to grass pollen, CC and AT treatment showed a therapeutic effect on the signs and symptoms of allergic conjunctivitis. A CC enhanced the use of EH alone and was the only treatment to reduce symptoms to baseline within 1 hour of antigenic challenge. Signs of allergic conjunctivitis generally were reduced most by a combination of a CC in combination with ATs or EH.