ABSTRACT
BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II is an extremely rare autosomal recessive inborn error of fatty acid beta oxidation and branched-chain amino acids, secondary to mutations in the genes encoding the electron transfer flavoproteins A and B (ETFs; ETFA or ETFB) or ETF dehydrogenase (ETFDH). The clinical manifestation of MADD are heterogeneous, from severe neonatal forms to mild late-onset forms. CASE PRESENTATION: We report the case of a preterm newborn who died a few days after birth for a severe picture of untreatable metabolic acidosis. The diagnosis of neonatal onset MADD was suggested on the basis of clinical features displaying congenital abnormalities and confirmed by the results of expanded newborn screening, which arrived the day the newborn died. Molecular genetic test revealed a homozygous indel variant c.606 + 1 _606 + 2insT in the ETFDH gene, localized in a canonical splite site. This variant, segregated from the two heterozygous parents, is not present in the general population frequency database and has never been reported in the literature. DISCUSSION AND CONCLUSION: Recently introduced Expanded Newborn Screening is very important for a timely diagnosis of Inherited Metabolic Disorders like MADD. In some cases which are the most severe, diagnosis may arrive after symptoms are already present or may be the neonate already died. This stress the importance of collecting all possible samples to give parents a proper diagnosis and a genetic counselling for future pregnacies.
Subject(s)
Multiple Acyl Coenzyme A Dehydrogenase Deficiency , Oxidoreductases Acting on CH-NH Group Donors , Electron-Transferring Flavoproteins/genetics , Electron-Transferring Flavoproteins/metabolism , Humans , Infant, Newborn , Iron-Sulfur Proteins , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/diagnosis , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/genetics , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/metabolism , Mutation , Oxidoreductases Acting on CH-NH Group Donors/genetics , Oxidoreductases Acting on CH-NH Group Donors/metabolismABSTRACT
OBJECTIVE: This work aims to clarify the histogenesis of the cells forming RA pannus: the pannocytes. METHODS: 15 patients with seropositive RA; 5 controls with post-traumatic knee effusion and 5 with OA knee effusion were included in the study. Synovial tissues and fluids, collected during diagnostic arthrocentesis, were used as a source of cells to be cultured. Viable staining and cytocentrifugation were performed. Cell phenotype was investigated by immunofluorescence assays after different culture periods. Cells were also studied by immunohistochemistry to determine the presence of CD5, CD68:KP-1, CD68:PG-M1, vimentin, cytokeratin, a-SM-Actin. RESULTS: Cells derived from RA samples were sub-divided into two population of lymphocyte-like and macrophage-like cells. Phenotypical characteristics of the first one were analysed after 6 days of culture and suggested they were T lymphocytes. The other population could grow in vitro for undefined time resembling the neoplastic-like proliferation previously described for pannocytes. Phenotypic characterization excluded that these cells were lymphocytes, monocyte-macrophages, fibroblasts, myofibroblasts, endothelial cells or keratinocytes. On the contrary, immunohistochemistry demonstrated that 100% of pannocytes were vimentin positive and 75% of these cells expressed also CD68:KP-1. CONCLUSIONS. The results exclude that pannocytes originate from monocyte-macrophages or from fibroblasts, but strongly support the hypothesis that they belong to the family of primitive embryonal connective tissue-forming cells (residue of the primitive mesenchymal tissue).
