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WOS: 000442229500021, PubMed ID: 30101073, 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., Vitaflo, We thank Vitaflo for supporting the publication cost of this paper.

WOS: 000423688500002, PubMed ID: 29370874, Background: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency. Methods: A cross-sectional questionnaire (13 questions) was emailed to all members of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder dietitians. Results: Thirty-six centres reported the dietary prescriptions of 126 patients with FBPase deficiency. Patients' age at questionnaire completion was: 1-10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age was: 16y, 2% (n = 2). Seventy-five per cent of centres advocated dietary restrictions. This included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%). Twenty-five per cent of centres (n = 9), advised no dietary restrictions when patients were well. A higher percentage of patients aged >16y rather than 16y, 85% (n = 35/41). Patients classified as having a normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y, and 58% in >16y, but it was unclear if fasting tolerance was biochemically proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to limit overnight fasting in 47 patients regardless of their actual fasting tolerance (37%). All centres advocated an emergency regimen mainly based on glucose polymer for illness management. Conclusions: Although all patients were prescribed an emergency regimen for illness, use of sucrose and fructose restricted diets with UCCS supplementation varied widely. Restrictions did not relax with age. International guidelines are necessary to help direct future dietary management of FBPase deficiency., ERDF - Programa Operacional Competitividade e Internacionalizacao - COMPETE [POCI-01-0145-FEDER-007746]; FCT - Fundacao para a Ciencia e a Tecnologia within CINTESIS, RD Unit [UID/IC/4255/2013], This article was supported by ERDF through the operation POCI-01-0145-FEDER-007746 funded by the Programa Operacional Competitividade e Internacionalizacao - COMPETE2020 and by National Funds through FCT - Fundacao para a Ciencia e a Tecnologia within CINTESIS, R&D Unit (reference UID/IC/4255/2013).

Resumen: Introducción: Los marcadores séricos son de gran utilidad como indicadores de enfermedad celíaca (EC), si bien la biopsia intestinal sigue siendo el patrón oro para establecer el diagnóstico. La positividad de los anticuerpos antitransglutaminasa tisular humana de clase IgA (AATGt-IgA) y los anticuerpos antiendomisio IgA (AAE-IgA) se correlaciona con histología intestinal patológica. La atrofia vellositaria (Marsh 3) representa una característica fundamental para el diagnóstico de EC. El tipo correspondiente a Marsh 2 (hiperplasia críptica) es debatido como lesión propia de la EC. Objetivo: Comprobar el nivel de AATGt-IgA que corresponda a un valor predictivo positivo (VPP) de lesión histológica de 100% para el diagnóstico de EC. Material y métodos: Serie de 120 pacientes menores de 14 años sin déficit de IgA sometidos a biopsia intestinal con serología positiva tanto a AATGt-IgA como AAE-IgA. Para los AATGt-IgA según recomendación del fabricante se consideran valores positivos cifras ≥ 16 U/ml. Se establece el VPP de AATGt-IgA a diferentes puntos de corte. Resultados: La distribución de los hallazgos histológicos en relación con el punto de corte de AATGt-IgA pone de manifiesto el mayor número de lesiones patológicas a medida que aumenta los valores de AATGt-IgA. Con valores del punto de corte por encima de 7,5-10,6 se corresponde con Marsh 2 2,1% y Marsh 3 93,4%; por encima de 10,6 veces el punto de corte, todas las biopsias se catalogan como Marsh 3 (100%). El VPP considerando solo las lesiones Marsh 3 alcanza bajo valor (55%) con serología positiva a AATGt-IgA con valores comprendidos entre 16 y 67 U/ml (1 a 4,2 x punto de corte), y elevado valor (92%) para las concentraciones entre 68 y 118 U/ml (4,3 a 7,4 x punto de corte), y para los casos con 69-170 U/ml (7,5 a 10,6 x punto de corte) (93%). Por encima de 170 U/ml (> 10,6 x punto de corte) el VPP es 100%. Conclusiones: El uso de valores superiores al punto de corte recomendado lógicamente debe mejorar aún más la especificidad del test y su VPP. En el 31,6% de los pacientes con positividad para AATGt-IgA y AAE-IgA (38/120) hubiera sido posible diagnosticar la enfermedad sin biopsia intestinal al contar con VPP de 100%. Como existen diversos kits comerciales con distintos puntos de corte, no es posible la estandarización de los resultados, por lo que hay que ser muy cautos para establecer recomendaciones basadas en los valores de AATGt-IgA. Abstract: Introduction: Serological markers are of great interest in coeliac disease (CD), although intestinal biopsy is still the gold standard for establishing the diagnosis. Tissue transglutaminase IgA antibodies (AATGt-IgA) and antiendomysial antibodies IgA (AAE-IgA) are closely correlated to intestinal damage observed in biopsies. Villous atrophy (Marsh 3) plays a major role in CD diagnosis. Marsh 2 stage (crypt hyperplasia) as a CD marker is still under debate. Objective: To ascertain an AATGt-IgA level that corresponds to a positive predictive value (PPV) of 100% for a histological CD diagnosis. Material and methods: A series of 120 patients younger than 14 years, non- IgA deficient, who underwent an intestinal biopsy and were positive for both serological markers (AATGt-IgA and AAE-IgA). For AATGt-IgA, according to the manufacturer's recommendations, a value greater than 16 IU/mL is considered as a positive value. The PPV of AATGt was determined for different cut-off points. Results: The histological findings distribution is directly correlated to the AATGt-IgA cut-off point. When the cut-off point is set above 7.5-10.6 times the commercial reference value, there is a 2.1% of Marsh 2 lessions and 93.4% of Marsh 3; above 10.6 times the reference value, all biopsies where Marsh 3 (100%). The PPV that considers Marsh 3 is (93.4%). The PPV, for considering Marsh 3 is low (55%) when AATGt-IgA serology is positive with levels between 16 and 67 IU/ml (1-4.2 times the cut-off point) and a higher value (92%) for concentrations between 68 and 118 IU/ml (4.3-7.4 times) and for cases with 69-170 IU/ml (7.5-10.6 times); above 170 IU/ml (>10.6 times) PPV is 100%. Conclusion: The use of values higher than the recommended cut-off point must logically improve specificity and PPV. In 31.6% patients positive for AATGt-IgA and AAE-IgA (38/120) it would have been possible to diagnose the disease without intestinal biopsy as of the PPV was 100%. It is not possible to standardise results as there are different commercial kits with variable cut-off points, so we must be cautious when setting recommendations based on AATGt-IgA.

Background/Aims Range and severity of symptoms hugely variable in aminoacidopathies, mainly diagnosed during acute episodes. Tandem Mass spectrometry (Ms/Ms) used in our unit since 2010 for diagnosing asymptomatic infants (very important for prognosis). Methods Retrospective, descriptive study in which field data were collected from clinical histories of patients diagnosed of aminoacidopathies (excluding phenylcetonuria) since 2000 till 2012. Results 30 children detected. 22/30 male; 24/30 caucasians. 10/30 diagnosed by newborn screening, all of them asymptomatic: 1 methylmalonic acidemia (MMA), 3 glutaric aciduria type 1, 2 homocystinuria, 2 methylcrotonylglycinuria, 1 hipermetioninemia and 1 maple syrup urine disease. 20/30 diagnosed because of clinical symptoms, 2/20 since MS/MS newborn screening was performed. Mean age of clinical debut in intoxication type aminoacidopathies was 64.5 days (median 8 days). Most frequent symptoms were clouding of consciousness (9/20), convulsions (2/20) and apnoea (2/20). Laboratory results showed metabolic acidosis (6/20), hyperammonemia (8/20), coagulation defects (4/20) and hipoglycemia. Main complications were: shock (9/20), multiple organ failure (5/20), coagulopathy (4/20), brain injury (1/20), liver failure (1/20) and seizures (2/20). The final diagnosis was: 5 OTC-defficiency, 2 citrullinemia, 3 methylmalonic acidemia, 1 3-OH-metilglutaric aciduria, 1 glutaric aciduria type 1, 1 metilglutaconic acidemia, 1 trimethylaminuria, 1 propionic acidemia, 2 tyrosinemia and 3 homocystinuria. Ventilatory support needed in 13/20, vasoactive agents 11/20, peritoneal dialysis 8/20, continuous veno-venous haemofiltration 4/20. 8 patients died; among survivors, 2/12 madurative failure, 3/12 serious neurological sequelae, 1/12 liver failure, needing transplantation. Conclusions Aminoacidopathies diagnosed by Ms/Ms start early with treatment. Wide range of presentation symptoms and findings.

Introduction Referring to the use of statins for hyperlipemia in children, it is not yet clearly defined who must be treated (recent recommendations focused on older than 8 years) and also the frequency of short and long-term toxicity. Methods Retrospective, descriptive study of patients, 10 year-old or younger, under statin treatment, followed in our Unit. Epidemiology, treatment and side-effects data were analized. Results Twelve children met inclusion criteria; 7/12 female and 11/12 caucasian. Main diagnosis was familiar hypercholesterolemia (10/12); 1/12 hypertriglyceridemia and 1/12 nefrotic syndrome. Positive family history of cardiovascular events: 5/12 (no death among first degree relatives). Mean age at diagnosis was 5.3 years. All of them were asymptomatic. 8/12 had been treated previously (7/12 resins, 1/12 cholesterol absorption inhibitor). Statin treatment starting age was 8.6 years, 4/12 younger than 8 year-old (minimum age: 5.2 years). Atorvastatin used in 10/12, lovastatin 1/12, simvastatin 1/12; initial dose was always 10 mg/day. The average levels before treatment were: LDL 235 mg/dL, total cholesterol 324.7 mg/dL. In one 10 year-old patient (40 mg/day lovastatin) muscular pain was reported with a CPK increase; side-effects stopped once the statin dose was reduced to 20mg/day. Besides, no adverse effect was reported. The highest dose achieved was 40 mg/day. Patients follow-up varies from 9 months to 4 years. Conclusions It remains unclear whether statins could be started before 8 year-old. From our experience, no adverse effects were found in that group. Dose had to be increased to 20–40 mg/day in order to achieve objectives.