RESUMEN
BACKGROUND: A subset of patients with phenylketonuria benefit from treatment with tetrahydrobiopterin (BH4), although there is no consensus on the definition of BH4 responsiveness. The aim of this study therefore was to gain insight into the definitions of long-term BH4 responsiveness being used around the world. METHODS: We performed a web-based survey targeting healthcare professionals involved in the treatment of PKU patients. Data were analysed according to geographical region (Europe, USA/Canada, other). RESULTS: We analysed 166 responses. Long-term BH4 responsiveness was commonly defined using natural protein tolerance (95.6%), improvement of metabolic control (73.5%) and increase in quality of life (48.2%). When a specific value for a reduction in phenylalanine concentrations was reported (n = 89), 30% and 20% were most frequently used as cut-off values (76% and 19% of respondents, respectively). When a specific relative increase in natural protein tolerance was used to define long-term BH4 responsiveness (n = 71), respondents most commonly reported cut-off values of 30% and 100% (28% of respondents in both cases). Respondents from USA/Canada (n = 50) generally used less strict cut-off values compared to Europe (n = 96). Furthermore, respondents working within the same center answered differently. CONCLUSION: The results of this study suggest a very heterogeneous situation on the topic of defining long-term BH4 responsiveness, not only at a worldwide level but also within centers. Developing a strong evidence- and consensus-based definition would improve the quality of BH4 treatment.
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Biopterinas/análogos & derivados , Fenilalanina/genética , Fenilcetonurias/tratamiento farmacológico , Biopterinas/efectos adversos , Biopterinas/uso terapéutico , Canadá/epidemiología , Europa (Continente)/epidemiología , Humanos , Fenilalanina/sangre , Fenilalanina Hidroxilasa/genética , Fenilcetonurias/sangre , Fenilcetonurias/epidemiología , Fenilcetonurias/patología , Estados Unidos/epidemiologíaRESUMEN
Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the 1-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTDs). GIF and FUT2 are 2 genes associated with the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as predictors of severe birth defects, in 183 aborted fetuses compared with 375 healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy newborns and to 8.1% in NTD fetuses (odds ratio 17.8 [95% confidence interval CI: 4.0-77.6]). The frequency of FUT2 rs601338 secretor variant was not different among groups. The GIF 290C heterozygous/FUT2 rs601338 secretor variant combined genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and healthy newborns (P < .0001). This GIF/FUT2 combined genotype has been previously reported in children with congenital gastric intrinsic factor (GIF) deficiency, with respective consequences on B12 binding activity and GIF secretion. In conclusion, a genotype reported in congenital GIF deficiency produces also severe forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the CUBN/GIF pathway could play a role in the neural tube closure mechanisms.
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Fucosiltransferasas/genética , Predisposición Genética a la Enfermedad/genética , Factor Intrinseco/genética , Mutación , Defectos del Tubo Neural/genética , Polimorfismo de Nucleótido Simple , Estudios de Cohortes , Feto/metabolismo , Frecuencia de los Genes , Genotipo , Heterocigoto , Humanos , Recién Nacido , Análisis de Secuencia de ADN/métodos , Galactósido 2-alfa-L-FucosiltransferasaRESUMEN
OBJECTIVES: Rhabdomyolysis and myalgia are common conditions, and mutation in the ryanodine receptor 1 gene (RYR1) is suggested to be a common cause. Due to the large size of RYR1, however, sequencing has not been widely accessible before the recent advent of next-generation sequencing technology and limited phenotypic descriptions are therefore available. MATERIAL & METHODS: We present the medical history, clinical and ancillary findings of patients with RYR1 mutations and rhabdomyolysis and myalgia identified in Denmark, France and The Netherlands. RESULTS: Twenty-two patients with recurrent rhabdomyolysis (CK > 10 000) or myalgia with hyperCKemia (>1.5 × ULN) and a RYR1 mutation were identified. One had mild wasting of the quadriceps muscle, but none had fixed weakness. Symptoms varied from being restricted to intense exercise to limiting ADL function. One patient developed transient kidney failure during rhabdomyolysis. Two received immunosuppressants on suspicion of myositis. None had episodes of malignant hyperthermia. Muscle biopsies were normal, but CT/MRI showed muscle hypertrophy in most. Delay from first symptom to diagnosis was 12 years on average. Fifteen different dominantly inherited mutations were identified. Ten were previously described as pathogenic and 5 were novel, but rare/absent from the background population, and predicted to be pathogenic by in silico analyses. Ten of the mutations were reported to give malignant hyperthermia susceptibility. CONCLUSION: Mutations in RYR1 should be considered as a significant cause of rhabdomyolysis and myalgia syndrome in patients with the characteristic combination of rhabdomyolysis, myalgia and cramps, creatine kinase elevation, no weakness and often muscle hypertrophy.
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Mialgia/genética , Rabdomiólisis/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Adolescente , Adulto , Niño , Dinamarca , Femenino , Francia , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Mialgia/fisiopatología , Países Bajos , Fenotipo , Rabdomiólisis/fisiopatología , Síndrome , Adulto JovenRESUMEN
The current standard of care for diagnosis of severe intellectual disability (ID) and epileptic encephalopathy (EE) results in a diagnostic yield of â¼50%. Affected individuals nonetheless undergo multiple clinical evaluations and low-yield laboratory tests often referred to as a 'diagnostic odyssey'. This study was aimed at assessing the utility of clinical whole-exome sequencing (WES) in individuals with undiagnosed and severe forms of ID and EE, and the feasibility of its implementation in routine practice by a small regional genetic center. We performed WES in a cohort of 43 unrelated individuals with undiagnosed ID and/or EE. All individuals had undergone multiple clinical evaluations and diagnostic tests over the years, with no definitive diagnosis. Sequencing data analysis and interpretation were carried out at the local molecular genetics laboratory. The diagnostic rate of WES reached 32.5% (14 out of 43 individuals). Genetic diagnosis had a direct impact on clinical management in four families, including a prenatal diagnostic test in one family. Our data emphasize the clinical utility and feasibility of WES in individuals with undiagnosed forms of ID and EE and highlight the necessity of close collaborations between ordering physicians, molecular geneticists, bioinformaticians and researchers for accurate data interpretation.
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Exoma/genética , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Trastornos del Neurodesarrollo/genética , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Pruebas Diagnósticas de Rutina/métodos , Pruebas Diagnósticas de Rutina/tendencias , Epilepsia/diagnóstico , Epilepsia/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Masculino , Trastornos del Neurodesarrollo/diagnóstico , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
INTRODUCTION: The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre, retrospective cohort study. METHODS: Diagnostic age of PKU and co-existent condition, treatment regimen, and impact of co-existent condition on blood phenylalanine (Phe) control and PKU management were reported. RESULTS: 30 patients (11 males and 19 females), with PKU and a co-existent condition, current median age of 14 years (range 0.4 to 40 years) from 13 treatment centres from Europe and Turkey were described. There were 21 co-existent conditions with PKU; 9 were autoimmune; 6 gastrointestinal, 3 chromosomal abnormalities, and 3 inherited conditions. There were only 5 cases of parental consanguinity. Some patients required conflicting diet therapy (n=5), nutritional support (n=7) and 5 children had feeding problems. There was delayed diagnosis of co-existent conditions (n=3); delayed treatment of PKU (n=1) and amenorrhea associated with Grave's disease that masked a PKU pregnancy for 12 weeks. Co-existent conditions adversely affected blood Phe control in 47% (n=14) of patients. Some co-existent conditions increased the complexity of disease management and increased management burden for patients and caregivers. CONCLUSIONS: Occurrence of co-existent disease is not uncommon in patients with PKU and so investigation for co-existent disorders when the clinical history is not completely consistent with PKU is essential. Integrating care of a second condition with PKU management is challenging.
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Enfermedades Autoinmunes/terapia , Aberraciones Cromosómicas , Manejo de la Enfermedad , Enfermedades Gastrointestinales/terapia , Fenilalanina/sangre , Fenilcetonurias/terapia , Adolescente , Adulto , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Biopterinas/análogos & derivados , Biopterinas/uso terapéutico , Niño , Preescolar , Consanguinidad , Dieta , Europa (Continente) , Femenino , Enfermedades Gastrointestinales/sangre , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/diagnóstico , Humanos , Lactante , Masculino , Fenilcetonurias/sangre , Fenilcetonurias/complicaciones , Fenilcetonurias/diagnóstico , Embarazo , Estudios Retrospectivos , TurquíaRESUMEN
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.
Asunto(s)
Manejo de la Enfermedad , Educación en Salud/métodos , Encuestas Epidemiológicas , Terapia Nutricional/métodos , Fenilcetonurias/dietoterapia , Adolescente , Adulto , Niño , Consejo/educación , Dieta , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Padres/educación , Cooperación del Paciente , Médicos , Proyectos Piloto , Adulto JovenRESUMEN
In our phenylketonuria (PKU) cohort of 120 patients, we uncovered a couple of cases of undiagnosed mild phenylketonuria (mPKU)/hyperphenylalaninemia (mHPA) in maternal parents of the PKU cohort. This finding prompted us to evaluate the risk of either mild phenylketonuria or mild hyperphenylalaninemia in the parent population whose children were diagnosed with hyperphenylalaninemia (HPA). Taking into account the phenylalanine hydroxylase (PAH) mutation carrier frequency and the PAH mild mutation rate, we estimated that the prevalence of the parental mPKU/mHPA varied widely, from 1/74 in Turkey to 1/708 in Lithuania. The benefits of the parental detection procedure described here are the prevention of further maternal PKU syndrome, the follow-up of the newly detected patients and the accuracy of the genetic counseling provided to these families. This very simple procedure should be incorporated into neonatal PKU management of the hospitals in countries where a routine systematic neonatal screening is operational.
Asunto(s)
Tasa de Mutación , Fenilalanina Hidroxilasa/genética , Fenilcetonuria Materna/diagnóstico , Fenilcetonurias/diagnóstico , Femenino , Asesoramiento Genético , Conocimientos, Actitudes y Práctica en Salud , Humanos , Recién Nacido , Lituania/epidemiología , Masculino , Mutación , Tamizaje Neonatal , Padres , Linaje , Fenilcetonuria Materna/epidemiología , Fenilcetonuria Materna/genética , Fenilcetonuria Materna/prevención & control , Fenilcetonurias/epidemiología , Fenilcetonurias/genética , Fenilcetonurias/prevención & control , Embarazo , Medición de Riesgo , Turquía/epidemiologíaRESUMEN
Patients with phenylketonuria (PKU) encompass an 'at risk' group for micronutrient imbalances. Optimal nutrient status is challenging particularly when a substantial proportion of nutrient intake is from non-natural sources. In PKU patients following dietary treatment, supplementation with micronutrients is a necessity and vitamins and minerals should either be added to supplement phenylalanine-free l-amino acids or given separately. In this literature review of papers published since 1990, the prevalence of vitamin and mineral deficiency is described, with reference to age of treatment commencement, type of treatment, dietary compliance, and dietary practices. Biological micronutrient inadequacies have been mainly reported for zinc, selenium, iron, vitamin B12 and folate. The aetiology of these results and possible clinical and biological implications are discussed. In PKU there is not a simple relationship between the dietary intake and nutritional status, and there are many independent and interrelated complex factors that should be considered other than quantitative nutritional intake.
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Suplementos Dietéticos , Micronutrientes/deficiencia , Minerales/administración & dosificación , Estado Nutricional , Fenilcetonurias/fisiopatología , Deficiencia de Vitamina B 6/etiología , Vitaminas/administración & dosificación , Adolescente , Adulto , Envejecimiento , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Micronutrientes/administración & dosificación , Necesidades Nutricionales , Cooperación del Paciente , Fenilcetonurias/complicaciones , Fenilcetonurias/dietoterapia , Adulto JovenRESUMEN
For almost all patients with PKU, a low phenylalanine diet is the basis of the treatment despite a widely varying natural protein tolerance. A vitamin and mineral supplement is essential and it is commonly added to a phenylalanine-free (phe-free) source of L-amino acids. In PKU, many phe-free L-amino acid supplements have age-specific vitamin and mineral profiles to meet individual requirements. The main micronutrient sources are chemically derived and their delivery dosage is usually advised in three or more doses throughout the day. Within the EU, the composition of VM (vitamin and mineral) phe-free L-amino acid supplements is governed by the Foods for Special Medical Purposes (FSMP) directive (European Commission Directive number 1999/21/EC and amended by Directive 2006/141/EC). However the micronutrient composition of the majority fails to remain within FSMP micronutrient maximum limits per 100 kcal due to their low energy content and so compositional exceptions to the FSMP directive have to be granted for each supplement. All patients with PKU require an annual nutritional follow-up, until it has been proven that they are not at risk of any vitamin and mineral imbalances. When non-dietary treatments are used to either replace or act as an adjunct to diet therapy, the quality of micronutrient intake should still be considered important and monitored systematically. European guidelines are required about which micronutrients should be measured and the conditions (fasting status) for monitoring.
Asunto(s)
Micronutrientes/administración & dosificación , Minerales/administración & dosificación , Fenilcetonurias/dietoterapia , Vitaminas/administración & dosificación , Suplementos Dietéticos , Unión Europea , Humanos , Micronutrientes/efectos adversos , Minerales/efectos adversos , Fenilalanina/deficiencia , Fenilalanina/metabolismo , Vitaminas/efectos adversosRESUMEN
Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor-free or essential L-AAs are important in all these conditions. Optimal long-term outcome depends on early diagnosis and good metabolic control, but because of the rarity and severity of conditions, randomized controlled trials are scarce. In all of these disorders, it is commonly described that dietary adherence deteriorates from the age of 10 years onwards, at least in part representing the transition of responsibility from the principal caregivers to the patients. However, patients may have particular difficulties in managing the complexity of their treatment because of the impact of the condition on their neuropsychological profile. There are little data about their ability to self-manage their own diet or the success of any formal educational programs that may have been implemented. Trials conducted in non-phenylketonuria (PKU) patients are rare, and the development of specialist L-AAs for non-PKU AA disorders has usually shadowed that of PKU. There remains much work to be done in refining dietary treatments for all conditions and gaining acceptable dietary adherence and concordance, which is crucial for an optimal outcome.
Asunto(s)
Aminoácidos/administración & dosificación , Dieta con Restricción de Proteínas , Suplementos Dietéticos , Enfermedades Metabólicas/dietoterapia , Cooperación del Paciente , Humanos , Conducta Social , Trastornos Innatos del Ciclo de la Urea/dietoterapiaRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs mostly in the context of insulin resistance and obesity. It has rapidly evolved into the most common cause of liver disease among children. The incidence is high in obese children and a greater risk of disease progression is associated with severe obesity, highlighting the role of nutrition. To date, there is no consensus on NAFLD management. This is a narrative review of clinical studies on the potential benefit of nutritional interventions, including lifestyle modifications, vitamins, docosahexaenoic acid, and probiotics in children with NAFLD. The Comité de nutrition de la Société Française de Pédiatrie (CN-SFP) emphasizes the effect of limiting added sugar intake, i.e., fructose or sucrose-containing beverages, and promoting physical activity in the care of NAFLD.
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Estilo de Vida , Enfermedad del Hígado Graso no Alcohólico/terapia , Estado Nutricional , Obesidad Infantil/complicaciones , Niño , Dieta , Carbohidratos de la Dieta , Grasas de la Dieta , Ácidos Grasos Omega-3 , Fructosa/efectos adversos , Humanos , Hígado , Obesidad Infantil/terapia , ProbióticosRESUMEN
Baby-led weaning (BLW), proposed as a new form of complementary feeding, has emerged as a real trend phenomenon in the media. Infants are seated at the family table from the age of 6 months, facing the foods they grab and bring to their mouth: they decide which foods they want to eat and what amount. The consumption of mashed foods and the use of a spoon are totally discouraged. BLW is increasingly used in nurseries and centers of young children. A bibliographic search carried out between 2000 and 2021 found 423 articles, of which 38 were selected. The clinical studies selected are 11 cross-sectional observational studies and two randomized controlled studies. BLW promotes breastfeeding, the early introduction of morsels, the respect of the child's appetite, the use of unprocessed foods, and the choice of "homemade" and friendliness. These benefits can nonetheless be reached with usual complementary feeding (SCF), according to current recommendations. Other benefits are claimed without scientific evidence such as easier achievement of dietary complementary feeding and an optimal growth with prevention of excess weight gain. BLW has some obvious downsides. The infant may not get enough energy, iron, zinc, vitamins, and other nutrients, or too much protein, saturated fat, salt, or sugar. The risk of choking, which must be distinguished from the physiological gagging reflex, has not been ruled out by scientific studies. Currently, the Nutrition Committee of the French Pediatric Society considers that the data published to date in terms of benefits and risks of BLW do not lend themselves to advice for this practice in preference over SCF carried out according to current recommendations.
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Conducta Alimentaria , Fenómenos Fisiológicos Nutricionales del Lactante , Lactancia Materna , Niño , Preescolar , Estudios Transversales , Conducta Alimentaria/fisiología , Femenino , Humanos , Lactante , Conducta del Lactante , Alimentos Infantiles , Fenómenos Fisiológicos Nutricionales del Lactante/fisiología , Hierro , Azúcares , Vitaminas , Destete , ZincRESUMEN
The same basic principles are used to deliver dietary treatment in PKU that was developed sixty years ago. Dietary treatment is undoubtedly very successful, but it has gradually evolved and been guided commonly by individual experience and expert opinion only. There is little international consensus about dietary practice with improvements in specialist dietary products concentrating on taste and presentation rather than nutritional composition. Many areas of dietary treatment have not been rigorously examined. In particular, the amino acid and micronutrient profile of Phenylalanine-free (phe-free) amino acids requires further study. In different formulations of phe-free amino acids, there are variations in the amino acid patterns as well the amount of essential and non essential amino acids per 100g/amino acids. The amount of added tyrosine and branch chain amino varies substantially, and in PKU specifically, there is little data about their relative absorption rates and bioavailability. In phe-free amino acids, there is evidence suggesting that some of the added micronutrients may be excessive and so the source and amount of each micronutrient should be scrutinized, with a need for the development of international nutritional composition standards exclusively for these products. There is a dearth of data about the life-long phenylalanine tolerance of patients or the nutritional state of adult patients treated with diet. There is a growing need to measure body composition routinely in children with PKU and with the rise in childhood obesity, it is important to measure body fatness and identify those who are at greatest risk of 'co-morbidities' of obesity. There is necessity for international collaboration to ensure robust data is collected on many basic aspects of nutritional care to guarantee that diet therapy is delivered to the highest standard.
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Estado Nutricional/fisiología , Fenilcetonurias/fisiopatología , Composición Corporal , Proteínas en la Dieta/metabolismo , Humanos , Micronutrientes/metabolismo , Fenilalanina/deficiencia , Fenilalanina/metabolismoRESUMEN
BACKGROUND: Deficiency of mitochondrial trifunctional protein (MTP) is caused by mutations in the HADHA and HADHB genes, which have been mostly delineated at the genomic DNA level and have not been always elucidated. AIM: To identify mutations in a French cohort of 52 MTP deficient patients and the susceptibility of mutations generating premature termination codons (PTCs) to the nonsense mRNA mediated decay (NMD). METHODS: Mutation screening in fibroblasts was performed at the cDNA level and real-time RT-PCR was used to compare the levels of the different PTC-bearing mRNAs before and after a treatment of fibroblasts by emetine, a translation inhibitor. RESULTS: A mutation detection rate of 100% was achieved. A total of 22 novel mutations were identified, including a large-sized genomic deletion in HADHB gene. A high proportion of all identified mutations were non-sense, frameshift and splicing mutations, generating (PTCs), distributed essentially on HADHA coding regions. We could demonstrate that the majority of mutations resulting in PTCs conform to the established rules governing the susceptibility to NMD. CONCLUSION: Our results emphasize the value of cDNA analysis in the characterization of HADHA and HADHB mutations and further strengthen the model of haploinsufficiency as a major pathomechanism in MTP defects.
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ADN Complementario/genética , Trastornos del Metabolismo de los Lípidos/genética , Enfermedades Mitocondriales/genética , Proteínas Mitocondriales/genética , Complejos Multienzimáticos/genética , Mutación , Secuencia de Bases , Estudios de Cohortes , Femenino , Francia , Haploinsuficiencia , Humanos , Masculino , Proteína Trifuncional Mitocondrial , Subunidad alfa de la Proteína Trifuncional Mitocondrial , Subunidad beta de la Proteína Trifuncional Mitocondrial , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADNRESUMEN
Twenty-five novel mutations including duplications in the ATP7A gene. Menkes disease (MD) and occipital horn syndrome (OHS) are allelic X-linked recessive copper deficiency disorders resulting from ATP7A gene mutations. MD is a severe condition leading to progressive neurological degeneration and death in early childhood, whereas OHS has a milder phenotype with mainly connective tissue abnormalities. Until now, molecular analyses have revealed only deletions and point mutations in both diseases. This study reports new molecular data in a series of 40 patients referred for either MD or OHS. We describe 23 point mutations (9 missense mutations, 7 splice site variants, 4 nonsense mutations, and 3 small insertions or deletions) and 7 intragenic deletions. Of these, 18 point mutations and 3 deletions are novel. Furthermore, our finding of four whole exon duplications enlarges the mutation spectrum in the ATP7A gene. ATP7A alterations were found in 85% of cases. Of these alterations, two thirds were point mutations and the remaining one third consisted of large rearrangements. We found that 66.6% of point mutations resulted in impaired ATP7A transcript splicing, a phenomenon more frequent than expected. This finding enabled us to confirm the pathogenic role of ATP7A mutations, particularly in missense and splice site variants.
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Adenosina Trifosfatasas/genética , Proteínas de Transporte de Catión/genética , Cutis Laxo/genética , Síndrome de Ehlers-Danlos/genética , Duplicación de Gen/genética , Síndrome del Pelo Ensortijado/genética , Mutación Puntual/genética , Eliminación de Secuencia/genética , ATPasas Transportadoras de Cobre , Cutis Laxo/patología , Síndrome de Ehlers-Danlos/patología , Exones/genética , Femenino , Perfilación de la Expresión Génica , Reordenamiento Génico/genética , Humanos , Masculino , Síndrome del Pelo Ensortijado/patología , Reacción en Cadena de la Polimerasa Multiplex , Mutación Missense/genética , Sitios de Empalme de ARN/genéticaRESUMEN
BACKGROUND: In type I congenital disorders of glycosylation (CDG I), proteins necessary for the biosynthesis of the lipid-linked oligosaccharide (LLO) required for protein N-glycosylation are defective. A deficiency in guanosine diphosphate-mannose: GlcNAc(2)-PP-dolichol mannosyltransferase-1 (MT-1) causes CDG Ik (OMIM 608540), and only five patients, with severe multisystemic clinical presentations, have been described with this disease. Objective To characterise genetic, biochemical and clinical data in five new CDG Ik cases and compare these findings with those of the five previously described patients. Methods LLO biosynthesis was examined in skin biopsy fibroblasts, mannosyltransferases were assayed in microsomes prepared from these cells, and ALG1-encoding MT-1 was sequenced at the DNA and complementary DNA levels. Clinical data for the five new patients were collated. RESULTS: Cells from five patients with non-typed CDG I revealed accumulations of GlcNAc(2)-PP-dolichol, the second intermediate in the biosynthesis of LLO. Assay of MT-1, -2 and -3, the first three mannosyltransferases required for extension of this intermediate, demonstrated only MT-1 to be deficient. DNA sequencing of ALG1 revealed nine different mutations, seven of which have not been previously reported. Clinical presentations are severe, with dysmorphias, CNS involvement and ocular disturbances being prevalent. CONCLUSIONS: 5 patients with CDG Ik are described, and their identification reveals that in France, this disease and CDG Ib (mannose phosphate isomerase deficiency: OMIM 602579) are the most frequently diagnosed CDG I after CDG Ia (phosphomannomutase 2 deficiency: OMIM 601785) and substantiate previous observations indicating that this disease presents at the severe end of the CDG I clinical spectrum.
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Trastornos Congénitos de Glicosilación/genética , Manosiltransferasas/genética , Mutación , Secuencia de Bases , Células Cultivadas , Preescolar , Trastornos Congénitos de Glicosilación/clasificación , Análisis Mutacional de ADN , Exones/genética , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Lactante , Lipopolisacáridos/biosíntesis , Masculino , Manosiltransferasas/deficiencia , Manosiltransferasas/metabolismoRESUMEN
BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. MAIN BODY: In 2017 the first European PKU Guidelines were published. These guidelines contained evidence based and/or expert opinion recommendations regarding diagnosis, treatment and care for patients with PKU of all ages. This manuscript is a supplement containing the practical application of the dietary treatment. CONCLUSION: This handbook can support dietitians, nutritionists and physicians in starting, adjusting and maintaining dietary treatment.
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Fenilalanina Hidroxilasa , Fenilcetonurias , Dieta , Humanos , Fenilalanina , TirosinaRESUMEN
An amendment to this paper has been published and can be accessed via the original article.
RESUMEN
Foods for special medical purposes (FSMPs) with a protein fraction made of hydrolyzed rice protein (HRPs) have been on the market in Europe since the 2000s for the treatment of cow's milk protein allergy (CMPA). HRP formulas (HRPFs) are proposed as a plant-based alternative to cow's milk protein-based extensively hydrolyzed formulas (CMP-eHF) beside the soy protein formulas whose use in CMPA is controversial. HRPFs do not contain phytoestrogens and are derived from non-genetically modified rice. HRPFs are strictly plant-based apart from the addition of vitamin D3 (cholecalciferol). As the amino acid content of rice proteins differs from that of human milk proteins, the protein quality of these formulas is improved by supplementation with free lysine, threonine, and tryptophan. The consumption of HRPFs has risen: for example, in France HRPFs account for 4.9% in volume of all formulas for children aged 0-3 years. Several studies have shown the adequacy of HRPFs in treating CMPA. They ensure satisfactory growth from the 1st weeks of life for infants and toddlers, both in healthy children and in those with CMPA. HRPFs can be used to treat children with CMPA either straightaway or in second intention in cases of poor tolerance to CMP-eHF for organoleptic reasons or for lack of efficacy. In France, the cost of HRPFs is close to that of regular infant or follow-on formulas.
Asunto(s)
Fórmulas Infantiles , Hipersensibilidad a la Leche/dietoterapia , Oryza , Proteínas de Vegetales Comestibles/administración & dosificación , Hidrolisados de Proteína/administración & dosificación , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/análisis , Humanos , Lactante , Fórmulas Infantiles/química , Lípidos/administración & dosificación , Lípidos/análisis , Proteínas de la Leche/efectos adversos , Proteínas de Vegetales Comestibles/análisis , Hidrolisados de Proteína/análisisRESUMEN
Avoidant/restrictive food intake disorder (ARFID) has recently been added to the DSM V (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) as a new class of eating disorders (EDs). ARFID is characterized by a lack of interest in eating or avoiding specific types of foods because of their sensory characteristics. This avoidance results in decreased nutritional intake, eventually causing nutritional deficiencies. In severe cases, ARFID can lead to dependence on oral nutritional supplements, which interferes with psychosocial functioning. The prevalence of ARFID can be as high as 3% in the general population, and it is often associated with gastrointestinal symptoms and mainly appears in children with anxiety disorders. Given the high prevalence of ARFID, a rapid and systematic nutrition survey should be conducted during every pediatric consultation. Its treatment should also be adapted depending on the severity of the nutritional problem and may involve hospitalization with multidisciplinary care (pediatrician, nutritional therapist, dietitian, psychologists, and speech therapists).