Relationship between mutation genotype and biochemical phenotype in a heterogeneous Spanish phenylketonuria population.

Genotyping of the phenylalanine hydroxylase (PAH) gene offers a new tool for characterizing patients with phenylketonuria (PKU), refining the diagnosis and aiding in the prediction of the clinical outcome and in the implementation of a more adequate treatment. The primary goal of this work was the detailed study of the different allele combinations and the metabolic phenotypes in Spanish PKU patients in order to understand better the clinical heterogeneity of PAH deficiency in our population. The results show that the disease phenotype is a consequence of a combination of mutations at the PAH locus and this observation is valid throughout the spectrum of clinical and biochemical varieties found in Spanish PKU patients. A stronger correlation was found between the predicted residual activity, when known from previous in vitro studies of the mutant proteins, and the Phe tolerance than between the predicted residual activity and the inverse of Phe levels at diagnosis. The observed genotype-phenotype correlations and the available data on the in vitro residual activity of the mutant proteins has enabled the estimation of the severity of most of the mutations found in Spain. This study includes relevant data for clinicians and pediatricians adding to the present knowledge which relates allelic PAH genotypes to biological phenotypes.

Effect of serum from breast- or formula-fed infants on polymorphonuclear leukocyte function.

The aim of the present study was to determine the influence of serum from formula and breast-fed infants on neutrophil function (as measured by the attachment and phagocytosis of Candida albicans) as well as the chemoattractant activity of the serum. The results indicate that: (a) serum from breast-fed infants induces a greater chemoattractant activity in neutrophils than serum from 3-month-old formula-fed infants; (b) the highest values of the attachment capacity were obtained after incubation of neutrophils with serum from 1-month-old breast-fed infants; and (c) serum from breast-fed infants induces a greater phagocytic capacity against C. albicans in neutrophils than serum from formula-fed infants.

[Non-ketotic hyperglycinemia. Transient neonatal form]. / Hiperglicinemia no cetósica. Forma neonatal transitoria.

We report a patient with neonatal epilepsy, with no pattern of burst-suppression, secondary to the transient form of nonketotic hyperglycinemia. Biochemical normalization at two weeks of age was followed by a good clinical evolution and neurological normality at one year of age. The patient showed markedly retarded myelination and microcysts in the frontal white matter, both transitory and with subsequent neuroradiological normalization. Only five patients have been previously described with this clinical variant, there being suspicion of a glycine cleavage system deficiency due to neonatal enzymatic immaturity.

Serum hemolytic and bactericidal activity in breast and formula-fed infants.

Whether formula or breast feeding influences the functional activity of the complement system from birth to three months of age has been studied. The classical pathway was evaluated by assessing hemolytic activity, based on the capacity of the intact complement system to lyse sheep erythrocytes when coated with specific antibodies. The bactericidal activity of the serum against Staphylococcus aureus and Escherichia coli was used to evaluate the alternative complement pathway. Sera were obtained from neonates (40 +/- 2 weeks of gestation), and one-month or three-month old infants, fed either breast or formula. Control serum was obtained from healthy adults between 22 and 30 years of age. The hemolytic capacity of serum from breast-fed infants of one month and three months of age was significantly greater than that of the serum from infants which had been fed formula milk.

[Reversible neuropsychological deterioration associated with valproate]. / Deterioro neuropsicológico reversible asociado a valproato.

Valproate (VPA) is indicated for treatment of febrile convulsions (FC) and very infrequently is associated with impairment of cognitive functions. We present a 8 years old girl treated with VPA for FC who manifest a dramatic behavioral and intellectual disorder confirmed by neuropsychological tests. Three weeks after a reduction of VPA dosis we observed a spectacular clinical improvement. Then, medication was discontinued with normalization of the neuropsychological items, till now, more than one year later. At all time plasmatics levels of VPA were in range and we never observed direct toxicity by the drug. This is an exceptional picture, and for our knowledge never has been reported during treatment of FC. We think that is important to inform of drug-induced abnormalities like this for avoid unnecessary exams to search for neurodegenerative disorders.

[Biochemical complications of experimental vesico-sigmoidostomy]. / Complicaciones bioquímicas de la vesicosigmoidostomía experimental.

Three experimental models of vesico-sigmoidostomy are studied (model-1, end to side V-S plus urethral ligation, model-2, end to end V-S, in "Y of Rous" plus urethral ligation and model-3, vesico-sigmoidoplasty), with aim of reproducing chemical imbalance observed in human subjects with ureterosigmoidostomy. Authors have evaluated clinical biochemical (serum acido-base balance, Cl, Na+, K+, BUN, creatinine, ammonia and albumin), and histologic variables in the first, third and fifth month after operation in 225 rats. Animal of model-1 presented more frequently than model-2 and model-3, alterations (hyperchloraemic acidosis, uraemia, hyperammonemia and hypoalbumin) as well as affectation of upper urinary system for acute or chronic pyelonephritis.

[Ring chromosome 18 46,XY,r(18)]. / Cromosoma 18 en anillo 46,XY,r(18).

Authors report a ring chromosome 18 (18 r) in a four year old boy, with low birth weight, retarded growth and development, microcephaly and plagiocephaly, horizontal nystagmus, ambiguous genitalia, clinodactyly of the fifth finger, distal axial triradius, whorls pattern in 8 fingers in dermatoglyphic. Serum IgA is lower than 3 mg/dl. Parents karyotype is normal.

[Fibrin-fibrinogen degradation products in cerebrospinal fluid of patients with meningococcal infections (author's transl)]. / Productos de degradación de la fibrina-fibrinógeno en el líquido cefalorraquídeo de pacientes con enfermedad meningocócica.

Fibrin degradation products (FDP) D and E, total protein, cell count, and alpha-1-antitrypsin levels have been measured in the cerebrospinal fluid (CSF), and FDP-D and E, and alpha-1-antitrypsin analyzed in serum in 13 cases of meningococcal disease, six with meningococcal septicemia and seven with meningitis. Neisseria meningitidis serotype B was the responsible agent in all cases. The following conclusions are obtained: 1) The presence of FDP in the CSF has no prognostic value, and its detection only in plasma does not exclude a fatal outcome. 2) Statistical analysis of the data suggests that the presence of FDP in the CSF is not the result of passive transfer from plasma but it indicates a meningeal inflammatory reaction. 3) Alpha-1-antitrypsin levels are elevated in meningococcal infections both in plasma and in the CSF, and they significantly correlate with the intensity of the fibrinolytic activity.