ABSTRACT
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.
Subject(s)
Phenylketonurias/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Genotype , Humans , Infant , Intelligence , Intelligence Tests , Male , Mutation , Phenotype , Phenylalanine/blood , Phenylalanine Hydroxylase/deficiency , Phenylalanine Hydroxylase/genetics , Phenylalanine Hydroxylase/metabolism , Phenylketonurias/psychology , Portugal , Statistics as TopicABSTRACT
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.
Subject(s)
Amino Acid Metabolism, Inborn Errors/physiopathology , Amino Acids, Branched-Chain/metabolism , Amino Acid Metabolism, Inborn Errors/metabolism , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , MaleSubject(s)
Biopterins/analogs & derivatives , Metabolism, Inborn Errors/diagnosis , Phenylketonurias , Phenylketonurias/diagnosis , Adolescent , Biopterins/deficiency , Child , Child, Preschool , Consanguinity , Female , Homovanillic Acid/urine , Humans , Hydroxyindoleacetic Acid/urine , Infant, Newborn , Male , Mass Screening , Metabolism, Inborn Errors/epidemiology , Metabolism, Inborn Errors/metabolism , Phenylalanine/blood , Phenylketonurias/prevention & control , Portugal/epidemiology , Pterins/cerebrospinal fluid , Pterins/urineABSTRACT
The authors studied the clinical and ultrastructural features of 8 cases of Neuronal Ceroid-Lipofuscinosis (NCL). Five cases of the late-infantile type and 3 cases of the juvenile type. The clinical diagnosis of all cases was confirmed by the electron microscopy analysis of the peripheral blood lymphocytes and biopsy material from the skin, palpebral conjunctiva, skeletal muscle and rectal mucosa. Our observations agree with previous reports concerning the predominance of curvilinear bodies in the cells of the late infantile type, and fingerprint-like structures in those of the juvenile type. The finding of parallel tubular arrays and NCL inclusions associated in the same lymphocyte (frequently in the same vacuole) suggests that those structures could be related to the metabolic error of NCL. Ultrastructural examination of microbuffycoats of peripheric blood lymphocytes is a simple, time-saving and reliable method that allows specific confirmation of a clinical diagnosis of Neuronal Ceroid-Lipofuscinosis.
Subject(s)
Lymphocytes/ultrastructure , Neuronal Ceroid-Lipofuscinoses/pathology , Adolescent , Adult , Biopsy , Child , Child, Preschool , Female , Humans , Male , Microscopy, ElectronABSTRACT
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.
Subject(s)
G(M1) Ganglioside/metabolism , Gangliosidoses/genetics , Biopsy , Bone Diseases/genetics , Edema/complications , Female , Gangliosidoses/pathology , Humans , Infant , Maxillofacial Development , Psychomotor Disorders/genetics , Skin/pathologyABSTRACT
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.
