Quality of dietary control in phenylketonuric patients and its relationship with general intelligence.

OBJECTIVES: Assessment of the quality of dietary treatment of phenylketonuria (PKU) patients and investigation of its relationship with the general intelligence of the patients. METHODS: Cross-sectional and longitudinal study of 105 PKU treated patients. The index of dietary control (IDC) was calculated as the phenylalanine (Phe) data reduction in half-year medians and the mean of all medians throughout the patient's life. We calculated four different IDCs related to age: IDC-A (< 6 years), IDC-B (6-12 years), IDC-C (13-18 years) and IDC-D (> 18 years). To evaluate the fluctuation of Phe values we calculated the standard error of the estimate of the regression of Phe concentration over age. Development quotient was calculated with the Brunet-Lezine test (< 4 years). Intelligence quotient was evaluated with the Kaufman Bit Intelligence Test (K-Bit), Wechsler Intelligence Scale for Children-Revised (WISC-R) and Wechsler Adult Intelligence Scale Third Edition (WAIS III). RESULTS: Cross-sectional study: The IDC in age groups were significantly different and so were the number of patients with good, acceptable and poor IDC related to age (p < 0.001). Sampling frequency was good in 72, acceptable in 23 and poor in 10 patients. The general intelligence (101 +/- 10) correlated negatively with the IDC (p < 0.0001) and Phe fluctuations (p < 0.004). Longitudinal study: Significant differences were observed between the IDC through the patients' lifetime except in the adolescent/adult period. CONCLUSIONS: 85% of PKU patients showed good/acceptable quality of dietary control. General intelligence correlates with the IDC at all ages, which highlights the importance of good control to achieve good prognosis.

Cognitive functions in patients with phenylketonuria in long-term treatment with tetrahydrobiopterin.

Cognitive functions were assessed in 9 patients with mild to moderate phenylketonuria (PKU) ranging from 6 to 18 years of age, who were in long-term treatment (>5 years) with 5-9 mg/kg/day tetrahydrobiopterin (BH4) on compassionate use, provided by Schircks Inc. An extensive study of cognitive functions (intelligence quotient (IQ), visuospatial, visual memory, fine motor, executive and attentional functions) was conducted, and behavior was assessed using the ADHD Rating Scale and the Behavior Rating Inventory of Executive Function (BRIEF). All patients had normal IQ (M=107, SD=10). The most notable area of impairment was fine motor function, but no significant difference was found between the PKU patients in BH4 treatment who participated in the current study and PKU patients in dietary treatment who participated in a previous study. These results, however, should be interpreted with caution. It is necessary to conduct further studies with a larger number of patients, using more sensitive tests of motor function and using the formulation of BH4 that is currently available.

Quality of dietary control in phenylketonuric patients and its relationship with general intelligence / Calidad del control de la dieta en pacientes fenilcetonúricos y su relación con la inteligencia general

Objectives: Assessment of the quality of dietary treatment of phenylketonuria (PKU) patients and investigation of its relationship with the general intelligence of the patients. Methods: Cross-sectional and longitudinal study of 105 PKU treated patients. The index of dietary control (IDC) was calculated as the phenylalanine (Phe) data reduction in half-year medians and the mean of all medians throughout the patient's life. We calculated four different IDCs related to age: IDC-A (< 6 years), IDC-B (6-12 years), IDC-C (13-18 years) and IDC-D (> 18 years). To evaluate the fluctuation of Phe values we calculated the standard error of the estimate of the regression of Phe concentration over age. Development quotient was calculated with the Brunet-Lezine test (< 4 years). Intelligence quotient was evaluated with the Kaufman Bit Intelligence Test (K-Bit), Wechsler Intelligence Scale for Children-Revised (WISC-R) and Wechsler Adult Intelligence Scale Third Edition (WAIS III). Results: Cross-sectional study: The IDC in age groups were significantly different and so were the number of patients with good, acceptable and poor IDC related to age (p < 0.001). Sampling frequency was good in 72, acceptable in 23 and poor in 10 patients. The general intelligence (101 ± 10) correlated negatively with the IDC (p < 0.0001) and Phe fluctuations (p < 0.004). Longitudinal study: Significant differences were observed between the IDC through the patients' lifetime except in the adolescent/adult period. Conclusions: 85% of PKU patients showed good/acceptable quality of dietary control. General intelligence correlates with the IDC at all ages, which highlights the importance of good control to achieve good prognosis (AU)

Objetivos: Evaluación de la calidad del control dietético en pacientes con fenilcetonuria (PKU) e investigación de su relacióncon el nivel de inteligencia. Métodos: Estudio transversal y longitudinal de 105 pacientes PKU en tratamiento dietético. El índice de control de la dieta (IDC) se ha calculado como la reducción de los valores de fenilalanina (Phe) a las medianas de cada 6 meses y la media de todas las medianas a lo largo de la vida del paciente. Se han calculado cuatro diferentes IDC según la edad: IDC-A (< 6 años), IDC-B (6-12 años), IDC-C (13-18 años) and IDC-D (> 18 años). Para evaluar las fluctuaciones de los valores de Phe hemos calculado el error estándar de la regresión estimada de la concentración de Phe según la edad. El índice de inteligencia se ha evaluado mediante el test de Brunet-Lezine (< 4 años) y el coeficiente de inteligencia mediante Kaufman Bit Intelligence Test (K-Bit), Wechsler Intelligence Scale for Children-Revised (WISC-R) y Wechsler Adult Intelligence Scale Third Edition (WAIS III). Resultados: Estudio transversal: El IDC en los diferentes grupos de edad es significativamente diferente y también lo son el número de pacientes con un IDC bueno, aceptable y malo en relación con la edad (p < 0,001). La frecuencia de controles de Phe fue buena en 72 pacientes, aceptable en 23 y mala en 10. La inteligencia general (101 ± 10) se correlaciona negativamente con el IDC (p < 0,0001) y con las fluctuaciones de Phe (p < 0,004). Estudio longitudinal: Se han observado diferencias significativas entre ICD a lo largo de la vida de los pacientes a excepción del período adolescencia/edad adulta. Conclusiones: El 85% de pacientes PKU mostraron una calidad del control de la dieta buena/aceptable. Los niveles de inteligencia general se correlacionan con el IDC en todas las edades, lo que muestra la importancia del buen control de la dieta para lograr un buen pronóstico (AU)

Do adult patients with phenylketonuria improve their quality of life after introduction/resumption of a phenylalanine-restricted diet?

AIM: To evaluate the possible influence of dietary treatment on the quality of life of adult patients with PKU (phenylketonuria) following late introduction or resumption of a Phe-restricted diet. METHODS: Fifteen adult patients with classical PKU (10F, 5M; mean age: 27.5 y, range: 16.4-37.5 y) were selected for the study. These patients had either resumed a restricted diet after a period of discontinuation, or were placed on a restricted diet after late diagnosis. All of them were interviewed about their quality of life using a 24-item questionnaire. RESULTS: The index of dietary control was poor (median Phe: 954 micromol/L) in 8/15 patients, regular (Phe: 514 micromol/L) in 4/15 and good (Phe: 354 micromol/L) in 3/15 patients. Fifty-three percent of patients reported that their state of health was very good, 47% described it as good, and 40% felt that their present health on-diet was better than it had been off-diet; 53% believed that they were calmer, quieter and less easily upset and 40% were more alert and were more able to maintain attention while on-diet. Thirty-three percent of the patients felt happier, and 27% felt more vital; 20% thought that they were less impulsive and aggressive, and that they were now less argumentative than before. Sixty percent of the patients felt that their quality of life had improved on-diet compared with the situation off-diet. CONCLUSION: More than half of our patients believed that their quality of life improved with a Phe-restricted diet; they reported feeling calmer, quieter, and less easily upset. Only 47% attained regular to good dietary control.

Acute necrotizing encephalopathy of childhood (infantile bilateral thalamic necrosis): two non-Japanese cases.

This report describes two Spanish cases of acute necrotizing encephalopathy of childhood, a rare disease first described in Japan by Mizuguchi and colleagues. Similar cases have been reported from Taiwan and other countries of the Far East. Two cases have been reported from the UK and one from the USA. The disease affects young children and is characterized by acute encephalopathy after a viral illness, with seizures and decreased levels of consciousness. The hallmark of the disease is diffuse and symmetrical CNS lesions of both thalami, internal capsules, upper brainstem tegmentum, and cerebral white matter. The aetiology is unknown but an infectious or parainfectious process seems likely. Because of the predominant involvement of the thalami, we propose the term 'infantile bilateral thalamic necrosis', a more specific term and one which distinguishes the entity from other basal ganglia diseases in childhood.

[Late onset of pseudobulbar paralysis and dystonia in a case of hemispheric cortical dysplasia]. / Inicio tardío de parálisis pseudobulbar y distonía en un caso de displasia cortical hemisférica.

The atypical clinical course of a young male with encephalopathy due to right hemispheric cortical dysplasia (pachygiria) is described. From the first months of life the course of the disease was a static encephalopathy with left hemiparesis, epilepsy and mild mental retardation. When he was 14 years old a subacute pseudobulbar palsy, dystonia and spread of the paresis to the right side occurred. Epileptic seizures, paroxysmal EEG abnormalities and drug ingestion were excluded. Neuropsychological studies showed a low level of cognitive functions, probably related to the malformative encephalopathy and expressive language deficit due to the pseudobulbar paresis. We speculate that this case could be an atypical case of delayed onset dyskiesia.

[Neurological development of very low birth weight infants (<1,501 gr) at two ears of age]. / Evolución neurológica a los dos años de edad en una población de recién nacidos de muy bajo peso (< 1.501 g).

The aim of this study is to analyse different aspects of the psychomotor development, during the first two years of the life, of 56 very low birth weight newborns (less of 1.501 g) that had completed a follow-up program. Of the results we have got, the most important are the following: 4 observations (7%) presented severe sequelae motor disability in a tetraparesis with sensorial defects in 3 of them and behavior disturbance (psychosis) with visual defect in the rest. Three observations (5.3%) presented moderate sequelae: all of them with motor disability (hemi- or tetraparesis) and cognitive deficiency. Me have to point out that in the two groups described above, the pathological signs were detected before the age of 6 months. Nine observations (16%) presented mild sequelae dominating language delayed (7% of whole sample) and transient abnormalities in 7 of them (12.5%). In the subgroup of small for gestational age newborns (21 observations), 28.5% presented mild sequelae, 14% transient abnormalities and no one presented severe or moderate sequelae. Although a long term follow-up is necessary in order to detect learning, cognitive, or behavior disturbances, that can just become evident later, we think that the attention of the deviations of the normality during the two first years of the life, would warn about possible future disturbances.

[Infantile spasms in children with Down's syndrome]. / Espasmos infantiles en niños con síndrome de Down.

Two hundred eighty six infants with Down syndrome have been studied. Infantile spasms have been identified in nine of them, in which background, EEG pattern and its evolution, modalities of treatment and its effects, neuroimaging and development course have been revised. None of these patients had either familiar or personal pathological antecedents. The pattern in the first EEG made was hypsarrhytmic in all cases except one which showed a multifocal paroxystical activity, with intermittent and bilateral bursts of spike-waves. The treatment first used was ACTH in four cases, valproate in three cases and phenobarbital in two cases (one of these associated with nitrazepam). The ACTH treatment was effective in seven infants, either was the first or the second choice. An infant in whom the first treatment with ACTH was not successful, responded to the association with valproate+clonazepam. One patient treated initially with phenobarbital+nitrazepam, having no response to different prescriptions, responded finally to the association of carbamacepin+vigabatrin. The first treatment with valproate or phenobarbital had no effect in all patients. The EEG pattern improved in all cases just after the treatment response. Normal tracing was found for a period of two months to three years. Cranial TC was performed to three infants showing one of them a discrete ventricular dilatation and periventricular calcifications that suggested tuberous sclerosis. It is important to point out that, although the good effect of therapy and EEG pattern normalization, the development is below what had been expected in children with Down syndrome. Behavioral problems have been found in seven (77.7%) of these children.(ABSTRACT TRUNCATED AT 250 WORDS)