ABSTRACT
BACKGROUND: Neonatal cholestasis (NC) is one of the most serious diseases in newborns and infants and results from metabolic disorders, such as Niemann-Pick type C (NPC), among other causes. OBJECTIVE: We evaluated the incidence of NPC in our NC plus lysosomal storage disease (LSD) suspicious neonates and infants series. METHODS: The study included children (≤3 years old) with a history of NC together with a suspicion of LSD, referred from Spanish Hospitals during the period 2011-2020. Screening for NPC was done by plasma biomarker assay (chitotriosidase activity and 7-ketocholesterol), and Sanger sequencing for NPC1 and NPC2 genes. RESULTS: We screened NPC disease in 17 patients with NC plus organomegaly and that were LSD suspicious, finding 5 NPC patients (29.4%) and 2 carriers. CONCLUSIONS: Our results emphasize the need to study NPC when NC and visceral enlargement arise in a newborn or infant.
Subject(s)
Cholestasis , Niemann-Pick Disease, Type C , Biomarkers/blood , Child, Preschool , Cholestasis/diagnosis , Cholestasis/epidemiology , Humans , Infant , Infant, Newborn , Mass Screening , Niemann-Pick Disease, Type C/diagnosis , Niemann-Pick Disease, Type C/epidemiologyABSTRACT
Several therapeutic options are available for type 1 Gaucher disease (GD1), including enzymatic replacement therapy (ERT) and substrate reduction therapy (SRT). Eliglustat is a selective inhibitor of glucosylceramide synthase that is extensively metabolized by CYP2D6 and, to a lesser extent by CYP3A4; it is also an inhibitor of the P-gp transporter. The aim of this study is to evaluate the metabolizer profile of these cytochrome isoforms in 61 GD1 patients, and to analyze interferences with concomitant therapies. Patients were selected from the Spanish Gaucher Disease Registry considering clinical data, GBA genotype, severity score index, comorbidities, concomitant drugs, type and response to therapy and adverse effects. The polymorphisms of CYP2D6, CYP3A4 and three ABCB1 transporter variants were analyzed by Polymerase Chain Reaction (PCR). The most frequent metabolizer profile was extensive or intermediate for CYP2D6, extensive for CYP3A4*1B and CYP3A4*22 and normal activity for ABCB1. Correlations between metabolizer profile and other variables were analyzed by multiple regression study. Twenty-eight patients received ERT, 17 eliglustat and seven miglustat. Forty-two patients (68.8%) had associated diseases and 54.5% were taking daily concomitant medication. Nine patients under eliglustat therapy received concomitant drugs that interact with the CYPs and/or ABCB1, five of these did not reach therapeutic goals and three presented mild or moderate adverse effects (headache and gastrointestinal disorders). Detailed analysis in four patients with TTT haplotype, corresponding to lack of activity of the transporter, was performed. In order to apply personalized medicine and avoid interferences and adverse effects, the individual CYP metabolizer profile and transporter must be considered when choosing the concomitant medication and/or making dose adjustments.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP3A/metabolism , Gaucher Disease/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP3A/genetics , Female , Gaucher Disease/genetics , Gaucher Disease/therapy , Haplotypes , Humans , Male , Middle Aged , Polymorphism, Genetic , Spain , Young AdultABSTRACT
No disponible
Subject(s)
Humans , Female , Adult , Niemann-Pick Disease, Type C/diagnosis , Gait Ataxia/etiology , Intellectual Disability , Intracellular Signaling Peptides and Proteins/genetics , Mutation , Niemann-Pick Disease, Type C/genetics , Ultrasonography , Vesicular Transport Proteins/geneticsSubject(s)
Niemann-Pick Disease, Type C/diagnosis , Adult , Female , Gait Ataxia/etiology , Humans , Intellectual Disability , Intracellular Signaling Peptides and Proteins/genetics , Mutation , Niemann-Pick C1 Protein , Niemann-Pick Disease, Type C/genetics , Ultrasonography , Vesicular Transport Proteins/geneticsABSTRACT
Forty-six patients submitted to operative choledochoscopy during biliary surgery are presented. Forty-two had benign diseases, principally calculi (38 cases), with only four patients presenting with malignant neoplasms. Our results bear out the effectiveness of operative choledochoscopy as a complement to cholangiography and conventional exploration of the bile duct, in significantly reducing the number of retained stones found, and in aiding other surgical procedures in the biliary tract.
Subject(s)
Common Bile Duct , Endoscopy , Gallstones/surgery , Cholangiopancreatography, Endoscopic Retrograde , Gallstones/diagnosis , Humans , Intraoperative Care/methodsABSTRACT
A case of papillary adenoma of the gallbladder unassociated with cholelithiasis and showing detachment of part of the growth with obstruction of the common bile duct is described. One the basis of a search of the literature, it would appear that this is the first time such a case has been reported. The bibliography is discussed and a distinction drawn between this kind of adenoma and other benign tumors of the gallbladder.
