Exploring drivers of liking of low-phenylalanine products in subjects with phenyilketonuria using check-all-that-apply method

The aim of the present study was to apply the Check-all-that-apply (CATA) method in an ambulatory context involving subjects with phenylketonuria (PKU) to obtain a sensory description and to find the drivers of liking of low-phenylalanine products (Glycomacropeptide vs. L-amino acids formulas). 86 subjects with PKU (age range: 8-55 years) evaluated 8 samples: 4 L-amino acid formulas and 4 Glycomacropeptide (GMP) formulas, flavored with neutral, chocolate, strawberry and tomato aromas. Participants were asked to indicate which sensory attributes characterized each formulations and to score the overall liking. Significant differences were found regarding liking scores (F = 65.29; p < 0.001). GMP samples flavored with chocolate and strawberry, described as sweets, with a mild and natural taste and odor, were the most appreciated. Overall, GMP formulas obtained higher liking scores compared to L-amino acid formulas. Tomato flavored samples, described as bitter, salty, with artificial color, with strong taste and odor, obtained the lowest scores. In conclusion, CATA questionnaire seems to be a suitable method also in ambulatory context since this approach suggested that different foods and beverages with GMP could be developed to improve dietary treatment compliance of subjects with PKU from school age onwards

Weaning practices in phenylketonuria vary between health professionals in Europe

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey (R)) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17-26 weeks in 85% (n=81/95) of centres, > 26 weeks in 12% (n=11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n=56/95) and fruit (34%, n=32/95). A Phe exchange system to allocate dietary Phe was used by 52% (n=49/95) of centres predominantly from Northern and Southern Europe and 48% (n=46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods. A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n=39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n=35/95) at infant age > 1y mainly from Southern Europe. 53% (n=50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.Peer reviewe

Early feeding practices in infants with phenylketonuria across Europe

Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey (R) questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months. 53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, >= 26 weeks in 12% and <17 weeks in 3%. Discussion: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.Peer reviewe

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Two successful pregnancies in a woman with Glycogen Storage Disease (GSD) Type III

BACKGROUND: Glycogen Storage Disease (GSD) type III is an autosomal recessive disease due to deficiency in glycogen debranching enzyme, amylo-1,6-glucosidase, which can present two different phenotypes (IIIa and IIIb). GSD IIIa occurs more frequently (85%), causing liver disease and other complications including skeletal myopathy and hypertrophic cardiomyopathy, while GSD IIIb is a purely hepatic form (2). Women affected by GSD type III do not seem to have any issues with fertility (although polycystic ovary disease can invariably be demonstrated); the disease may significantly interfere with the physiological course of pregnancy in terms of mother\u2019s and offspring\u2019s health, although overall the outcome of pregnancy is good. Energy and glucose demands fall with age; because of the increased metabolic demand during pregnancy, females affected by GSD III are more predisposed to hypoglycemia (1), ketosis and lactic acidosis, with higher risk of intrauterine growth retardation and low birth weight (2), lower IQ (3) and increased susceptibility to type 2 diabetes in elder life (4). Patients with GSD IIIa, particularly if a cardiomyopathy pre-exists, should be monitored carefully to avoid a possible deterioration of cardiac function during pregnancy and again in post-partum period (2). CASE REPORT: We report the case of two successful pregnancies in a 39-year-old woman affected by GSD type IIIa, under follow up at our Metabolic Department. Second-born of three siblings (the younger also affected), she was suspected with GSD IIIa at 8 months of age (clinical findings of hypoglycemia and hepatomegaly) and the diagnosis was then confirmed by liver biopsy (residual enzymatic activity: 0-zero). After medical assisted procreation with intracytoplasmic sperm injection, respectively at the age of 32 and 38 years, she carried out two pregnancies under a strict metabolic, nutritional and cardiac monitoring. During both pregnancies she required frequent meals and the early introduction of regular assumption of uncooked cornstarch (UCCS, 1 g/Kg at bedtime) in her dietetic therapy (consisting of roughly 55% carbohydrate-complex rather than simple- and 26% protein), in order to maintain a good metabolic profile. In addition to obstetric and metabolic care, she was closely monitored also by our cardiologic team, showing stable parameters even for cardiac function. Transthoracic echocardiograms showed mild left-ventricular hypertrophic cardiomyopathy, with maximal wall thickness (MWT) of 12 mm and normal systolic function. In both labours, she maintained normoglycemia by using a dextrose iv infusion alone, stopped two hours after deliveries when she was able to start again a regular feeding. Both infants were delivered vaginally at term, with adequate weight/length/head circumference for gestational age. Re-bound hypoglycemia was not observed either in patient or in newborns, but she preferred bottle-feeding for her babies. No development of hepatic adenomas was observed during pregnancy/post-partum period. Now, six months after the second childbirth, an increased cardiac MWT (20 mm) with stable ejection fraction was observed, requiring a deepened evaluation (cardiac MRI to identify an eventual development of cardiac fibrosis). DISCUSSION: Adaptations in maternal metabolism during a normal pregnancy are designed to ensure an adequate supply of nutrients and energy to the foetus; women with GSD III may not be able to match glucose production with increasing energy demands in pregnancy. Adults with GSD III often don\u2019t require additional feeds but metabolic evaluations during pregnancy have shown that nocturnal ketosis returns requiring late night and/or early morning cornflour supplements. Euglycemia needs to be maintained during pregnancy as lipolysis and ketosis increase the risk of fetal demise (1). Increased effort during labour can require an additional continue glucose supplementation, using a dextrose infusion and/or frequent meals with UCCS, with regular blood glucose testing. Cardiac disease in women with GSD III therefore has important implications in terms of management of pregnancy, pain relief, anaesthesia, fluid delivery, surgical intervention and the peri-partum period. Therefore females with GSD III in childbearing age should be counselled with regards to the potential impact of pregnancy on both their metabolic state and cardiac risk. CONCLUSION: This case strengthens the evidence that a careful and suitable management strongly concurs to positive outcomes in GSD III pregnancies. We can conclude that the course of pregnancy in patients affected by GSD III, in terms of mother\u2019s and offspring\u2019s health, can be optimal only taking into account some indispensable issues. References: (1) Bolton SD, Clark VA, Norman JE. Multidisciplinary management of an obstetric patient with glycogen storage disease type 3. Int J Obstet Anesth. 2012 Jan;21(1):86-9 (2) Ramachandran R, Wedatilake Y, Coats C, Walker F, Elliott P, Lee PJ, et al. Pregnancy and its management in women with GSD type III-a single centre experience. J Inherit Metab Dis. 2012 Mar;35(2):245-51. (3) Rizzo T, Metzger BE, Burns WJ, Burns K (1991) Correlations between antepartum maternal metabolism and child intelligence. N Engl J Med 325(13):911\u2013916 (4) Petry CJ, Hales CN (2000) Long-term effects on offspring of intrauterine exposure to deficits in nutrition. Hum Reprod Update 6(6):578\u201358

Sostituti proteici a base di aminoacidi vs glicomacropeptide: accettabilit&#224; e palatabilit&#224; in pazienti fenilchetonurici

Introduzione/background: Il trattamento della fenilchetonuria (PKU) prevede una dieta a basso e controllato apporto di fenilalanina (Phe). Lo scarso gradimento delle miscele aminoacidiche rappresenta un punto critico per la compliance. Lo scopo di questo studio \ue8 stato valutare propriet\ue0 sensoriali e gradimento di miscele di aminoacidi sintetici e formule a base di glicomacropeptide (GMP), proteina con basso contenuto di Phe, per selezionare le formulazioni pi\uf9 gradite. Metodi/pazienti: 53 pazienti PKU (et\ue0: 7-55 anni) hanno valutato in un\u2019unica seduta 8 campioni: 4 miscele di aminoacidi sintetici e 4 formule a base di GMP (Glytactin), aromatizzate con i medesimi aromi (neutro, cioccolato, pomodoro, fragola), e con apporto di proteine equivalenti pari a 5 g/100 ml. Per ciascun campione \ue8 stato chiesto di indicare quali descrittori, tra quelli proposti, caratterizzassero le formulazioni (CATA questionnaire) e il gradimento (scala lineare 100mm per adulti; scala figurata a 7 punti per bambini). Risultati: La Phe ematica media (DS) era di 256,7 (71,2) e di 501,6 (268,1) mol/L nei soggetti di et\ue0 inferiore e superiore a 12 anni, rispettivamente. Differenze significative sono state riscontrate tra i campioni per il gradimento (F: 28.06; p<0.001). I campioni di GMP aromatizzati con cioccolato e fragola, descritti come dolci, con gusto e odore delicato e naturale, sono risultati i pi\uf9 graditi. I campioni a base di aminoacidi sintetici sono risultati i meno graditi. I campioni al flavor pomodoro, descritti come salati, acidi, dal colore artificiale, con gusto e odore forte, hanno ottenuto i punteggi pi\uf9 bassi. Discussione: Dai risultati di questo studio emerge che le formule a base di GMP godono di una maggiore accettabilit\ue0 rispetto alle miscele aminoacidiche. Diversi alimenti e bevande, utilizzando prevalentamente gli aromi di cioccolato e fragola, potrebbero essere sviluppati partendo dal GMP per migliorare la compliance al trattamento dietetico dall\u2019et\ue0 scolare in poi

Early feeding practices in infants with phenylketonuria across Europe

BACKGROUND: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. METHODS: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. RESULTS: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%. DISCUSSION: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development