ABSTRACT
La deficiencia de biotinidasa es una enfermedad autosómica recesiva del metabolismo provocado por la ausencia o deficiencia de esta enzima. Clínicamente se caracteriza por síntomas neurológicos: convulsiones, ataxia, pérdida de la audición, atrofia óptica retardo del desarrollo, alopecia, problemas dermatológicos y alteraciones metabólicas (acidemia orgánica cuya descompensación puede llevar al coma o a la muerte). La importancia de tener un método cuantitativo en suero o plasma es importante para confirmar esta patología. Objetivo: Obtener valores de referencia de actividad de biotinidasa en la población de recién nacidos (RN) en una maternidad pública aplicando un método colorimétrico para la cuantificación de la enzima en suero. Material y métodos: Se obtuvieron muestras de pesquisa neonatal y sueros de una población de 238 RN. La actividad de la biotinidasa fue determinada utilizando un método colorimétrico (a partir de una modificación del kit Umtest Biotinidasa de Tecnosuma). Los valores de referencia obtenidos en nuestra población fueron compatibles con los hallados en la bibliografía. La población patológica testigo presentó valores concordantes con su clasificación diagnóstica.
Biotinidases Deficiency is an autosomal recessive disorder of metabolism caused by the absence or deficiency of the enzyme. The clinical setting characterizes for neurological (convulsions, ataxia, auditive loss, optic atrophy, development delay), alopecia, skin rash and metabolic alterations (organic acidemia whose decompensation can produce coma or death). The availability of a quantitative technique in blood serum is vital to confirm this pathology. Objective: To obtain reference values for a population of newborns at Public Maternity applying a colorimetric quantitative method in serum blood. Material and methods: Dried blood samples and sera were obtained from a population of 238 newborns. The activity of Biotinidase was measured by using a colorimetric method (from a modification of the Umtest Bionitidase kit of Tecnosuma). We obtained reference values in the analysed population, which are compatible with the bibliographic values used until now. The control pathological population had results according to its diagnostic classification.
Subject(s)
Humans , Infant, Newborn , Biotinidase Deficiency/complications , Biotinidase Deficiency/diagnosis , Nervous System Diseases/etiology , Neonatal Screening , Colorimetry/methods , Epidemiology, Descriptive , Hospitals, Municipal , Metabolic Diseases , Observational StudyABSTRACT
STAT5 proteins are components of the common growth hormone and interleukin 2 family of cytokines' signaling pathway. Mutations in the STAT5b gene, described in 2 patients, lead to growth hormone insensitivity that resembles Laron syndrome. Clinical immunodeficiency was also present, although immunologic defects have not been well characterized thus far. Here we describe a 16-year-old girl who suffered generalized eczema and recurrent infections of the skin and respiratory tract since birth. She also suffered severe chronic lung disease and multiple episodes of herpetic keratitis. Clinical features of congenital growth hormone deficiency were observed, such as persistently low growth rate, severely delayed bone age, and postnatal growth failure resulting from growth hormone resistance. This combined phenotype of growth hormone insensitivity and immunodeficiency was attributable to a homozygous C-->T transition that resulted in a nonsense mutation at codon 152 in exon 5 of the STAT5b gene. This novel mutation determined a complete absence of protein expression. The main immunologic findings were moderate T-cell lymphopenia (1274/mm3), normal CD4/CD8 ratio, and very low numbers of natural killer (18/mm3) and gammadelta T (5/mm3) cells. T cells presented a chronically hyperactivated phenotype. In vitro T-cell proliferation and interleukin 2 signaling were impaired. CD4+ and CD25+ regulatory T cells were significantly diminished, and they probably contributed to the signs of homeostatic mechanism deregulation found in this patient. This new case, in accordance with 2 previously reported cases, definitely demonstrates the significant role of the STAT5b protein in mediating growth hormone actions. Furthermore, the main immunologic findings bring about an explanation for the clinical immunodeficiency features and reveal for the first time the relevant role of STAT5b as a key protein for T-cell functions in humans.
Subject(s)
Immune System Diseases/etiology , Laron Syndrome/complications , Laron Syndrome/genetics , Mutation , STAT5 Transcription Factor/genetics , Adolescent , Female , HumansABSTRACT
CD4+ CD56+ malignancies have only recently been related to dendritic cell (DC) lineage. The few cases described, mostly adults and elderly, typically present with cutaneous lesions, followed by disseminated tumor localizations within a few months, with a generally very aggressive course and fatal outcome, despite the different therapeutic approaches employing chemotherapy and/or radiotherapy. Considering that leukemias in childhood and in adults are different diseases, we describe three pediatric cases to help compare the biological characteristics, immunophenotype, clinical features, treatment response and incidence of this disease in both age groups. From a total 1363 new patients with acute leukemia (AL), we report three cases with blasts of French - American - British L2 morphology, an absence of the most specific markers for myeloid, T or B lineage and lacking CD34, which led us to evaluate the blasts with an extensive panel of antibodies, including those related to the other putative pathways of lymphoid differentation: natural killer and DC. The cells expressed CD4, CD56, HLA-DR, BDCA-2 and BDCA-4. None of our cases presented with skin involvement. All three children showed good response to acute lymphoblastic leukemia (ALL) protocols, achieving complete remission even when one of the patients relapsed and received an allogeneic transplant. These findings, in spite of the small number of patients, suggest that the clinical course in children might be less aggressive, and that regular ALL protocols would be effective. We emphasize the importance of including antibodies for DC lineage in cases of CD34(-) unclassifiable AL to further characterize these rare cases (0.22%), considering that the tumor cell affiliation to DC lineage relies exclusively on immunophenotypic criteria.
