Stereotypies in Rett syndrome: analysis of 83 patients with and without detected MECP2 mutations.

BACKGROUND: Hand stereotypies are considered a hallmark of Rett syndrome (RTT) and are usually described as symmetric movements at the midline. However, related pathologies may show the same type of involuntary movement. Furthermore, patients with RTT also have stereotypies with other localizations that are less well characterized. METHODS: We analyzed stereotypies in 83 patients with RTT, 53 with and 30 without a mutation detected in the MECP2 gene. Patients were observed and videotaped always by the same pediatric neurologist. Stereotypies were classified, and data were submitted to statistical analysis for comparison of mutation-positive and -negative patients and analysis of their evolution with the disease. RESULTS: All the patients showed hand stereotypies that coincided with or preceded the loss of purposeful hand movements in 62% of the patients with MECP2 mutations. The hair pulling stereotypy was more frequent in the group with detected mutations, whereas hand washing was not. Hand gaze was absent in all RTT patients with MECP2 mutations. Patients with MECP2 mutations also had more varied stereotypies, and the number of stereotypies displayed by each patient decreased significantly with age in this group. In all patients, stereotypies other than manual tended to disappear with the evolution of the disease. CONCLUSIONS: Although symmetric midline hand stereotypies were not specific to patients with an MECP2 mutation, some of the other stereotypies seemed to be more characteristic of this group. In patients younger than 10 years and meeting the necessary diagnostic criteria of Rett syndrome, the association of hand stereotypies without hand gaze, bruxism, and two or more of the other stereotypies seemed to be highly indicative of the presence of an MECP2 mutation.

The correlation of genotype and phenotype in Portuguese hyperphenylalaninemic patients.

To understand the basis for the clinical heterogeneity of phenylalanine hydroxylase deficiency among Portuguese hyperphenylalaninemic patients, genotype-phenotype correlations were established. A group of 61 patients was completely genotyped, leading to the identification of 20 different mutant alleles in 36 different genotypic combinations, including a mutant allele not reported previously. The severity of those mutations found within this hyperphenylalaninemic population, which have not been previously expressed in vitro, were assessed. The results obtained by the present study exhibit a strong correlation between the predicted residual enzyme activity, as deduced from the genotype of the patients, and the biochemical phenotype represented by the diagnostic parameters (phenylalanine levels before the beginning of treatment and the dietary phenylalanine tolerance). It was observed that only a judicious follow-up and compliance with the appropriate diet permits the correct assessment of the clinical phenotype of the patients. Additionally, based upon the correlation observed between genotypes and diagnostic parameters, it was possible to predict the potential residual enzyme activity of those mutations (identified in our patients) which have not yet been studied in vitro.

[Branched chain amino acid diseases]. / Doenças dos aminoácidos de cadeia ramificada.

The authors present 19 cases of branched-chain AA catabolism disease: 9 Maple Syrup Urine Diseases, 6 Methylmalonic Acidemias, 2 Propionic Acidemias, 1 case of 3-OH-3-methylglutaryl-CoA-lyase deficiency and another of 2-methyl-ketoacetyl-CoA-thiolase deficiency. Fifteen are early neonatal forms and in 4 the onset occurred later. Fifteen patients (78.9%) needed one or several extra-corporal procedures either in the initial acute phase or during relapse. Fifteen patients presented several metabolic relapses, sometimes fatal (3 children). Global mortality was 26.3%, that is 5/19 patients: 4 children with neonatal forms, one with a later onset. Eleven patients (57.9%) had an IQ/DQ > or = 80: only 46.6% of the neonatal forms obtained these results, in contrast with all the late onset forms. Of the survivors, 9 (64.2%), presented a residual neurologic condition. The correct diagnostic and treatment procedures are defined and the need to consider the existence of these diseases at any age, particularly in the neonatal period, is stressed.

A case of GM1 gangliosidosis type I.

A six-month-old female gypsy child, the daughter of second degree cousins, born after a full-term pregnancy and normal delivery, is described. There was generalized neonatal edema. Abnormalities included psychomotor retardation from birth and progressive appearance of facial dysmorphism, organ enlargement, axial hypotonia, hypertonia in limbs, myoclonic jerks, optic atrophy and bilateral cherry-red spots. The diagnosis of GM1 type 1 gangliosidosis was confirmed by biochemical, enzymatic and ultrastructural findings.

[Phenylketonuria--physical and mental development of phenylketonuric children subjected to early treatment]. / Fenilcetonúria--desenvolvimento físico e mental de crianças fenilcetonúricas tratadas precocemente.

The Authors present the first clinical and laboratory assessment of 6 children with PKU, diagnosed and treated early, as a result of the application of the Early Diagnosis Programme in the southern part of the country, from April 1984 to November 1986. The main protein source used in the feeding of these patients was a phenylalanine-free mixture of amino-acids, with an excellent tolerance.