Dietary management of maternal phenylketonuria with glycomacropeptide and amino acids supplements: A case report.

BACKGROUND: In maternal PKU, protein substitute (PS) is provided by phenylalanine (PHE)-free l-amino acids (AA), but glycomacropeptide-based protein substitute (GMP) is an alternative consideration. OBJECTIVE: To describe the first Portuguese Maternal Phenylketonuria (MPKU) partially managed with GMP. CASE REPORT: A 31 year old MPKU female with classical PKU (mutations P281L/P281L), diagnosed by newborn screening, had a lifelong history of poor metabolic control. She has a history of partial bicornuate uterus and had a previous miscarriage in the first trimester. Pre-conception, her median blood PHE was 462 µmol/L but throughout pregnancy the median reduced to 258 µmol/L. GMP provided 30 g/day protein equivalent (46 mg/day PHE). Total protein equivalent from PS increased from 58 to 86 g/day during pregnancy but AA provided all additional protein equivalent intake. Both GMP and AA were well tolerated with no morning sickness. Normal morphologic evaluation and adequate fetal growth with cephalic biometry near the 5th percentile was determined. The infant was born at 39.3 weeks: weight 2570 g (3rd percentile), length 47.5 cm (10th percentile) and head circumference (HC) of 31.5 cm (1st percentile). In the neonatal period, the infant had craniofacial dimorphism with metopic suture prominence. Father also had bitemporal narrowing. By 12 months of age, the infant's weight (15th percentile), length (50th percentile) and HC (10th-50th percentile) were normal although bitemporal narrowing persisted. CONCLUSIONS: This is the first case reporting the use of GMP in MPKU. Its PHE content did not adversely affect metabolic control although it only provided part of the PS intake. Some intrauterine development delay occurred in the last trimester, although we consider that this is unlikely to be associated with MPKU syndrome or the use of GMP. More published data is essential to examine the impact of using GMP in MPKU on morning sickness severity and aversion, maternal weight gain, blood amino acid concentrations and variability of blood PHE concentrations.

Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source.

BACKGROUND/OBJECTIVES: Low phenylalanine (PHE), glycomacropeptide-based protein substitute (GMP) is an alternative to traditional L-amino acid supplements (AA) used in the dietary management of phenylketonuria (PKU). In a retrospective, longitudinal study, we report the nutritional status of PKU patients taking AA and GMP. SUBJECTS/METHODS: Eleven PKU patients aged 27±10 years (1 HPA, 4 mild and 6 classical PKU) on dietary treatment were evaluated (anthropometry, body composition, blood pressure measurements, biochemical markers including vitamin, mineral, lipids, carbohydrates and protein status/metabolism, and nutritional intake assessment) at two different annual reviews. The mean time taking AA was 13±5 months and GMP 13±7 months. Blood phenylalanine (PHE) and tyrosine (TYR) were analysed before and after GMP introduction. RESULTS: Both GMP and AA protein substitutes provided similar protein equivalent intake (0.85 vs 0.75 g/kg/day, P=0.182). In the GMP group, it contributed 57% (27-100%) of the protein substitute intake (with AA delivering the rest of protein substitute intake), providing an additional 34±12 mg/day PHE. Nutritional intake, anthropometry and body composition measurements were similar in both the groups. Median blood PHE did not change (P=0.594), although values within target range improved (36 vs 46%), but this was not statistically significant. Mean blood TYR increased (52.0±19.2 vs 63.2±25.6 µmol/l, P=0.033), and all biochemical markers remained stable, except for a lower A1C haemoglobin (P=0.011). CONCLUSIONS: Partial GMP contribution to total protein substitute intake did not affect nutritional status in patients with PKU. Blood PHE control was not adversely affected. The increased blood TYR after GMP introduction necessitates further study.

Protein substitutes for phenylketonuria in Europe: access and nutritional composition.

BACKGROUND/OBJECTIVES: Protein substitutes (PS) are an essential component in the dietary management of phenylketonuria (PKU). PS are available as phenylalanine-free amino-acid mixtures (AAM), glycomacropeptide-based PS (GMP) and large neutral amino acids (LNAA). There is a lack of information regarding their availability in different countries and comparison of their nutritional composition is limited. The objectives of this study were to identify the number of PS available in different European countries and Turkey and to compare their nutritional composition. SUBJECTS/METHODS: Members of the European Nutritionist Expert Panel on PKU (ENEP) (Portugal, Spain, Belgium, Italy, Germany, Netherlands, United Kingdom, Denmark and Turkey) provided data on PS available in each country. The nutritional composition of PS available in Portugal was analyzed. RESULTS: The number of PS available in each country varied from 30 (Turkey) to 105 (Germany), with a median of 64. GMP was available only in Portugal, whereas LNAA was an option in Portugal, Italy, Turkey and Denmark. Some PS were designed for weaning. Many PS did not contain added fat and fiber. GMP contained the highest carbohydrate (CHO) and energy content as well as higher LNAA content compared with AAM. Only one AAM contained added fructo-oligosaccharides and galacto-oligosaccharides. AAM designed for the first year of life had the highest CHO, fat and LNAA contribution. Liquid AAM had lower CHO and fat contents compared with powdered AAM, but contained higher LNAA. CONCLUSIONS: There was widely dissimilar numbers of PS available in different countries. Nutritional composition of different PS was variable and should be considered before prescription.

Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach.

BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

Nutrition education tools used in phenylketonuria: clinician, parent and patient perspectives from three international surveys.

BACKGROUND: Three international surveys were developed aiming to identify the current nutrition educational tools used in the management of phenylketonuria (PKU) and the perceived effectiveness of these tools by clinicians, parents and patients. METHODS: The first two surveys were distributed through the Metabolic Dietitians ListServe (pno-metabl@listserv.cc.emory.edu), and the third survey was distributed by international clinics and the National PKU Alliance website (www.npkua.org). A total of 888 responses (S1, n = 88; S2, n = 81; S3, n = 719) were collected from all three surveys. The surveys represent participants from 17 countries, in Europe; North America (USA and Canada); Mexico; Argentina; Turkey; Australia; and Africa (Tunisia). RESULTS: A consistent decline in 'parents as role models' as an educational tool was observed starting at age 10 years. Patients responded they feel their families are the most effective form of education, whereas handouts were selected as the least effective educational tool by patients. Parents responded they feel the most effective educational tool is one-on-one counselling. Patients and parents show a desirable trend in wanting to attend group clinic, even in centres where this type of educational tool is not offered. CONCLUSIONS: There was a discrepancy between clinicians and patient views regarding the perceived effectiveness of the nutrition education tools. Future research is needed surrounding the impact nutrition education may have on improved dietary compliance in patients with PKU.

Dietary practices in pyridoxine non-responsive homocystinuria: a European survey.

BACKGROUND: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. AIM: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. METHODS: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). RESULTS: 181 patients (73% >16 years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1-10 years, 90%; 11-16 years, 82%; and >16 years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1-10 years, 12 g; 11-16 years, 11 g; and >16 years, 45 g. With diet and betaine, median natural protein intake (g/day) by age was: 1-10 years, 13 g; 11-16 years, 20 g; and >16 years, 38 g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. CONCLUSION: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.

Dietary management of urea cycle disorders: European practice.

BACKGROUND: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. METHODS: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets. RESULTS: Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29; ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108; argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported. The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n=174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy supplements. CONCLUSIONS: Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required.

Vaccine immune response and interference of colostral antibodies in calves vaccinated against rabies at 2, 4 and 6 months of age born from antirabies revaccinated females.

Considering the high prevalence of rabies in cattle, we aimed to evaluate the interference of colostral antibodies transferred to calves after birth and the benefit of administering an antirabies vaccination in two-month-old calves compared to vaccinating at 4 and 6 months of age. Calves born from females revaccinated against rabies during the third trimester of pregnancy were studied. Forty-eight hours after parturition, blood samples from dams and offspring were collected, and antirabies neutralizing antibody titers were analyzed using the Rapid Focus Fluorescent Inhibition Test. We found that all calves had similar titers of antibodies transferred through the colostrum. Furthermore, none of the calves presented a satisfactory serological response after the first vaccination, but all had an appropriate response after revaccination. This study demonstrates that antirabies vaccination should be recommended for calves at two months of age in endemic and epizootic situations.

The effects of low-level laser on muscle damage caused by Bothrops neuwiedi venom

The present study aimed to assess the effects of low-level laser (660 nm) on myonecrosis caused by the insertion of Bothrops neuwiedi venom in the gastrocnemius muscle of rats. Male Wistar rats were divided into three groups (n equal 24 each): Group S (0.9 percent saline solution); Group V (venom) and Group VLLL (venom plus low-level laser). These categories were subdivided into four additional groups (n equal 6) based on the euthanasia timing (3 hours, 24 hours, 3 days and 7 days). The groups V and VLLL were inoculated with 100 miL of concentrated venom (40 mig/mL) in the gastrocnemius muscle. The muscle was irradiated using a gallium-aluminum-arsenide laser (GaAlAs) at 35 mW power and 4 J/cm² energy density for 3 hours, 24 hours, 3 days or 7 days after venom inoculation. To evaluate the myotoxic activity of the venom, CK activity was measured and the muscle was histologically analyzed. The low-level laser reduced venom-induced CK activity in the groups euthanized at 3 hours, 24 hours and 3 days (p smaller that 0.0001). Histological analysis revealed that low-level laser reduced neutrophilic inflammation as well as myofibrillar edema, hemorrhage and myonecrosis following B. neuwiedi envenomation. These results suggest that low-level laser can be useful as an adjunct therapy following B. neuwiedi envenomation.

Preoperative normovolemic hemodilution in aesthetic plastic surgery.

Normovolemic autotransfusion was used with 11 healthy females who were about to undergo multiple aesthetic plastic surgeries. After collecting a unit of blood immediately prior to surgery, a quick infusion of isotonic saline solution is made, at a 4-to-1 ratio, until reaching a hematocrit equal to or lower than 30%, thus inducing olighemia. The intended consequence is that blood lost during surgery be poor in red cell mass, which means reduced blood loss, leading to improved tissue oxygenation and decreased risk of thromboembolism. The blood thus collected is reinstilled at the end of the intervention. Results indicate that the technique can be prescribed and bring benefits to any patient entering surgery for which the surgeon anticipates heavy blood loss. The method proposed herein is presented as an alternative to homologous and autologous programmed transfusions and as equivalent to these in terms of volume replenishment.