Communicative and psycholinguistic abilities in children with phenylketonuria and congenital hypothyroidism

The Neonatal Screening for Inborn Errors of Metabolism of the Association of Parents and Friends of Special Needs Individuals (APAE) - Bauru, Brazil, was implanted and accredited by the Brazilian Ministry of Health in 1998. It covers about 286 cities of the Bauru region and 420 collection spots. Their activities include screening, diagnosis, treatment and assistance to congenital hypothyroidism (CH) and phenylketonuria (PKU), among others. In 2005, a partnership was established with the Department of Speech-Language Pathology and Audiology, Bauru School of Dentistry, University of São Paulo, Bauru, seeking to characterize and to follow, by means of research studies, the development of the communicative abilities of children with CH and PKU. OBJECTIVE: The aim of this study was to describe communicative and psycholinguistic abilities in children with CH and PKU. MATERIALS AND METHODS: Sixty-eight children (25 children aged 1 to 120 months with PKU and 43 children aged 1 to 60 months with CH) participated in the study. The handbooks were analyzed and different instruments were applied (Observation of Communication Behavior, Early Language Milestone Scale, Peabody Picture Vocabulary Test, Gesell & Amatruda's Behavioral Development Scale, Portage Operation Inventory, Language Development Evaluation Scale, Denver Developmental Screening Test, ABFW Child Language Test-phonology and Illinois Test of Psycholinguistic Abilities), according to the children's age group and developmental level. RESULTS: It was observed that the children with PKU and CH at risk for alterations in their developmental abilities (motor, cognitive, linguistic, adaptive and personal-social), mainly in the first years of life. Alterations in the psycholinguistic abilities were also found, mainly after the preschool age. Attention deficits, language and cognitive alterations were more often observed in children with CH, while attention deficits with hyperactivity and alterations in the personal-social, language and motor adaptive abilities were more frequent in children with PKU. CONCLUSION: CH and PKU can cause communicative and psycholinguistic alterations that compromise the communication and affect the social integration and learning of these individuals, proving the need of having these abilities assisted by a speech and language pathologist.

Separation of free amino acids in human plasma by capillary electrophoresis with laser induced fluorescence: potential for emergency diagnosis of inborn errors of metabolism.

Free amino acids (AAs) in human plasma are derivatized with 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) and analyzed by capillary electrophoresis (CE) with laser induced fluorescence (LIF) detection. The labeling procedure is significantly improved over results reported previously. Derivatization can be completed in 40 min, with concentrations as low as 4 x 10(-8) M successfully labeled in favourable cases. Twenty-nine AAs (including 2 internal standards) are identified and can be reproducibly separated in 70 min. Migration time RSD values for 23 of these AAs were calculated and found in the range from 0.5 to 4%. The rapid derivatization procedure and the resolution obtained in the separation are sufficient for a semi-quantitative, emergency diagnosis of several inborn errors of metabolism (IEM). Amino acid profiles for both normal donor plasma samples and plasma samples of patients suffering from phenylketonuria, tyrosinemia, maple syrup urinary disease, hyperornithinemia, and citrullinemia are studied.

Correlation between plasma and urine phenylalanine concentrations.

In this pilot study, we show that plasma phenylalanine concentration can be predicted from urine concentration if the age of the patient is taken into consideration. This observation could open the way to a new monitoring of phenylketonuric patients in which painful frequent blood sampling, mandatory to adapt the low phenylalanine diet, could be mostly replaced by urinalysis. Compliance to treatment would be improved and hence also the ultimate mental development. Since this study was based on a small number of patients, validation of the model in a large multicentric survey is needed before it can be recommended.

Interpretation of plasma amino acids in the follow-up of patients: the impact of compartmentation

Results of plasma or urinary amino acids are used for suspicion, confirmation or exclusion of diagnosis, monitoring of treatment, prevention and prognosis in inborn errors of amino acid metabolism. The concentrations in plasma or whole blood do not necessarily reflect the relevant metabolite concentrations in organs such as the brain or in cell compartments; this is especially the case in disorders that are not solely expressed in liver and/or in those which also affect nonessential amino acids. Basic biochemical knowledge has added much to the understanding of zonation and compartmentation of expressed proteins and metabolites in organs, cells and cell organelles. In this paper, selected old and new biochemical findings in PKU, urea cycle disorders and nonketotic hyperglycinaemia are reviewed; the aim is to show that integrating the knowledge gained in the last decades on enzymes and transporters related to amino acid metabolism allows a more extensive interpretation of biochemical results obtained for diagnosis and follow-up of patients and may help to pose new questions and to avoid pitfalls. The analysis and interpretation of amino acid measurements in physiological fluids should not be restricted to a few amino acids but should encompass the whole quantitative profile and include other pathophysiological markers. This is important if the patient appears not to respond as expected to treatment and is needed when investigating new therapies. We suggest that amino acid imbalance in the relevant compartments caused by over-zealous or protocol-driven treatment that is not adjusted to the individual patient's needs may prolong catabolism and must be corrected

Acompanhamento do aleitamento materno no tratamento de crianças com fenilcetonúria

A fenilcetonúria (PKU) ocorre na incapacidade para transformar fenilalanina em tirosina, trazendo efeitos tóxicos para o sistema nervoso central. Tradicionalmente, no tratamento da PKU, o aleitamento materno é substituído por fórmula láctea. Este estudo verificou os efeitos do aleitamento materno como fonte de fenilalanina no desenvolvimento de crianças com PKU. Participaram dez lactentes com PKU, que iniciaram o tratamento com a introdução de fórmula láctea antes dos 30 dias e que mantiveram o aleitamento materno por no mínimo 30 dias de vida após o início dos procedimentos. Os procedimentos basearam-se em estimar a ingestão de leite materno, com margem segura da concentração da fenilalanina, calculando o volume gástrico e oferecendo inicialmente fórmula láctea, seguida do aleitamento materno em demanda livre, em todas as mamadas. O tempo de amamentação variou de um mês e cinco dias a 14 meses. Os controles sanguíneos foram semanais. Se o nível sérico da fenilalanina estivesse >2 mg/dL e <6 mg/dL mantinha-se a prescrição; se estivesse <2 mg/dL, diminuía-se a fórmula láctea em 25%, aumentando indiretamente o aleitamento materno; se estivesse >6 mg/dL, aumentava-se a fórmula em 50%. Avaliou-se os níveis de fenilalanina, aplicou-se a Early Language Milestone Scale e Passos Básicos do Desenvolvimento. Foram considerados adequados aqueles lactentes que apresentaram índices normativos em todas as avaliações. Dos lactentes, 80% conseguiram manter limites seguros da fenilalanina e desenvolvimento nos índices normativos. Há viabilidade da continuidade do aleitamento materno no tratamento de crianças com PKU desde que os níveis de fenilalanina sejam rigorosamente controlados e que os efeitos do aleitamento materno para o desenvolvimento infantil sejam verificados.

Dental health in children with phenylketonuria PKU and other inborn errors of amino acid metabolism managed by diet /

"Supported in part by Maternal and Child Health, Grant No. MCS-000252-16 and by contributions to Friends of Metabolic Research."

Special low protein foods for phenylketonuria: availability in Europe and an examination of their nutritional profile

Background Special low protein foods (SLPF) are essential in the nutritional management of patients with phenylketonuria (PKU). The study objectives were to: 1) identify the number of SLPF available for use in eight European countries and Turkey and 2) analyse the nutritional composition of SLPF available in one of these countries. Methods European Nutritionist Expert Panel on PKU (ENEP) members (Portugal, Spain, Belgium, Italy, Germany, Netherlands, UK, Denmark and Turkey) provided data on SPLF available in each country. The nutritional composition of Portuguese SLPF was compared with regular food products. Results The number of different SLPF available in each country varied widely with a median of 107 [ranging from 73 (Portugal) and 256 (Italy)]. Food analysis of SLPF available from a single country (Portugal) indicated that the mean phenylalanine content was higher in low protein baby cereals (mean 48 mg/100 g) and chocolate/energy bars/jelly (mean 41 mg/100 g). The energy content of different foods from a sub-group of SLPF (cookies) varied widely between 23 and 96 kcal/cookie. Low protein bread had a high fat content [mean 5.8 g/100 g (range 3.7 to 10)] compared with 1.6 g/100 g in regular bread. Seven of the 12 SLPF sub-groups (58 %) did not declare any vitamin content, and only 4 (33 %) identified a limited number of minerals. Conclusions Whilst equal and free access to all SLPF is desirable, the widely variable nutritional composition requires careful nutritional knowledge of all products when prescribed for individual patients with PKU. There is a need for more specific nutritional standards for special low protein foods.