Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Very early onset inflammatory bowel disease (VEO-IBD) represents a diagnostic and treatment challenge. Here we present a case of VEO-IBD secondary to a mutation in BIRC4 gene, which encodes X-linked inhibitor of apoptosis protein (XIAP), in a 17-month-old boy with severe failure to thrive, intractable diarrhea, and hepatosplenomegaly. Endoscopy and histology identified only mild duodenitis and ileitis, but severe pancolitis with crypt abscesses and epithelium apoptosis. Minimal improvement in symptoms was achieved with total parenteral nutrition (TPN), intravenous (IV) corticosteroids, and tacrolimus, whereas induction and maintenance therapy with adalimumab led to complete remission. After 6 months, the patient developed hemophagocytic lymphohistiocytosis and eventually died due to multisystem organ failure. A review of the literature revealed that some patients with VEO-IBD secondary to XIAP deficiency develop symptoms that are refractory to medical and surgical management, while initial reports suggest that allogeneic hematopoietic stem cell transplantation (HSCT), with reduced intensity conditioning, can successfully induce long-lasting remission and may even be curative. We propose that in patients with XIAP deficiency a constellation of symptoms including colitis at an early age, severe failure to thrive, and splenomegaly/hepatosplenomegaly can identify a subgroup of patients at high risk of experiencing medically refractory IBD phenotype and increased mortality. Hematopoietic stem cell transplant should be considered early in these high-risk patients, as it may resolve both their intestinal inflammation and a risk of developing life threatening hemophagocytic lymphohistiocytosis .
 ...
PMID:Risk-factors Associated With Poor Outcomes in VEO-IBD Secondary to XIAP Deficiency: A Case Report and Literature Review. 3123 87

Hypercalcemia is an uncommon finding in children. Hypercalcemia has various etiologies including parathyroid dependent and independent mechanisms. Increased activity of the 1-alpha-hydroxylase enzyme in granulomatous diseases is a well-defined but an extremely rare cause of hypercalcemia in pediatric patients, particularly in infants. We describe the case of an infant who presented with failure to thrive, hepatosplenomegaly, and hypercalcemia who was initially treated with steroids but was later diagnosed with disseminated histoplasmosis in the absence of an underlying immunodeficiency. Extra caution should be used before considering steroids for the treatment of hypercalcemia and, whenever possible, steroids should not be initiated until a definite etiology is identified.
 ...
PMID:A Rare and Potentially Fatal Etiology of Hypercalcemia in an Infant. 3146 35

y+LAT1 (encoded by SLC7A7), together with y+LAT2 (encoded by SLC7A6), is the alternative light subunits composing the heterodimeric transport system y+L for cationic and neutral amino acids. SLC7A7 mutations cause lysinuric protein intolerance (LPI), an inherited multisystem disease characterized by low plasma levels of arginine and lysine, protein-rich food intolerance, failure to thrive, hepatosplenomegaly, osteoporosis, lung involvement, kidney failure, haematologic and immunological disorders. The reason for the heterogeneity of LPI symptoms is thus far only poorly understood. Here, we aimed to quantitatively compare the expression of SLC7A7 and SLC7A6 among different human cell types and evaluate y+LAT1 and y+LAT2 contribution to arginine transport. We demonstrate that system y+L-mediated arginine transport is mainly accounted for by y+LAT1 in monocyte-derived macrophages (MDM) and y+LAT2 in fibroblasts. The kinetic analysis of arginine transport indicates that y+LAT1 and y+LAT2 share a comparable affinity for the substrate. Differences have been highlighted in the expression of SLC7A6 and SLC7A7 mRNA among different cell models: while SLC7A6 is almost equally expressed, SLC7A7 is particularly abundant in MDM, intestinal Caco-2 cells and human renal proximal tubular epithelial cells (HRPTEpC). The characterization of arginine uptake demonstrates that system y+L is operative in renal cells and in Caco-2 where, at the basolateral side, it mediates arginine efflux in exchange with leucine plus sodium. These findings explain the defective absorption/reabsorption of arginine in LPI. Moreover, y+LAT1 is the prevailing transporter in MDM sustaining a pivotal role in the pathogenesis of immunological complications associated with the disease.
 ...
PMID:y+LAT1 and y+LAT2 contribution to arginine uptake in different human cell models: Implications in the pathophysiology of Lysinuric Protein Intolerance. 3170 28

A defect in the lipopolysaccharide-responsive beige-like anchor protein (LRBA) gene is a newly defined rare cause of primary immunodeficiency diseases, which manifests as immune dysregulation and humoral immune deficiency. LRBA deficiency is a combined immunodeficiency. A boy with LRBA deficiency is described in this report. He had been diagnosed with Evans syndrome in a haematology clinic. He was referred to an immunology and allergy clinic for frequent respiratory tract infections. He also had hepatosplenomegaly but no lymphadenopathy. Immunological evaluation revealed hypogammaglobulinaemia, increased double-negative T cells, decreased memory B cells and switched B cells, and an inverted CD4/CD8 ratio. LRBA deficiency was considered due to common variable immunodeficiency-autoimmune lymphoproliferative overlap syndrome. A homozygote mutation (c.1964C>T) in LRBA was found through exome sequencing. Gastrointestinal investigation was performed due to unexplained abdominal pain. It revealed atrophic gastritis, partial villous atrophy, and multiple gallstones. There was no chronic diarrhoea or failure to thrive. The abdominal pain disappeared after a cholecystectomy. Multiple gallstones have not been reported in other LRBA-deficient patients who also had autoimmune haemolytic anaemia. Multiple gallstones that require cholecystectomy can develop in LRBA-deficient patients during adolescence.
 ...
PMID:Development of multiple gallstones in a child with lipopolysaccharide-responsive beige-like anchor protein mutation. 3187 23

Background Peroxisomal biogenesis disorders (PBDs) include a miscellaneous group of diseases which cause serious multisystem disease. Mutations of 13 different PEX genes lead to PBDs including Zellweger syndrome (ZS). Different types of mutations of PEX1 and PEX10 genes are correlated with broad-range phenotypes of PBDs. Case presentation Patient 1 is a 4-month-old boy who was affected by myoclonic seizures, poor oral feeding since birth. The patient was hypotonic and had hepatosplenomegaly. Patient 2 is a 2-month-old boy who presented with decreased movement, severe hypotonia and failure to thrive. The laboratory studies of the patients revealed increased plasma very-long-chain fatty acids (VLCFAs). The genetic analyses of patient 1 demonstrated the first homozygous missense mutation in the PEX10 gene. A novel homozygous missense mutation was found in the PEX1 gene in patient 2. Conclusions This report highlights that the detected homozygous missense mutations of PEX10 and PEX1 genes and the substitutions of specific amino acids lead to the severe form of PBDs.
 ...
PMID:Two different missense mutations of PEX genes in two similar patients with severe Zellweger syndrome: an argument on the genotype-phenotype correlation. 3206 32


<< Previous 1 2 3 4 5 6 7 8 9 10