Report Of Clinical Features Research Articles

Prenatal-Onset Niemann–Pick Type C Disease with Nonimmune Hydrops Fetalis

Niemann-Pick type C (NPC; OMIM 257219) disease is a neurodegenerative lysosomal storage disorder characterized by accumulation of unesterified cholesterol in the lysosomal/late endosomal system. This autosomal recessive disorder occurs in approximately 1/150,000 births. The broad clinical spectrum ranges from a prenatal severe presentation to an adult-onset chronic neurodegenerative disease. Data about prenatal presentation of NPC are limited. A female newborn was born at 34(2) weeks' gestation with a birth weight of 3070 g, and transferred to the Neonatal Intensive Care Unit because of nonimmune hydrops fetalis (NIHF) and respiratory distress. On admission, a physical examination revealed skin edema, mild respiratory distress, and abdominal distention due to massive ascites. Hepatosplenomegaly and cholestasis increased progressively and bleeding diathesis occurred. Results of an abdominal ultrasonography showed hepatosplenomegaly and segmental multicystic dysplastic left kidney. Foamy cells with a lysosomal phospholipid storage pattern compatible with NPC were found in the bone marrow smear. Cultured fibroblasts showed a strongly elevated filipin staining (classical NPC cellular phenotype), establishing the diagnosis of NPC. The infant died on the 52(nd) day of life because of respiratory distress due to lung involvement of NPC, massive ascites, and progressive liver failure. Results of an autopsy showed multiorgan storage disease involving the liver, spleen, lymph nodes, thymus, lungs, and brain. Here, we present a preterm infant with NIHF as a sign of severe prenatal-onset NPC and review the literature.

Association of hypersensitivity reactions to oxaliplatin with cumulative dose of oxaliplatin.

584 Background: The incidence of hypersensitivity reactions (HSRs) to oxaliplatin (L-OHP) in colorectal cancer patients (CRC) receiving the 5-fluorouracil/leucovorin plus L-OHP (FOLFOX) regimen is reported to be 10 to 17%. There are several reports of clinical features of HSRs to L-OHP, but the relationship between HSRs and the cumulative dose of L-OHP has not been clarified. Methods: From August 2005 to July 2009, a total of 54 CRC patients who developed HSRs during treatment with mFOLFOX6 or mFOLFOX6 plus bevacizumab regimen as first-line treatment, were reviewed retrospectively. Within this patient group, sixteen patients had an L-OHP-free interval of at least three months or more. We investigated the clinical features of HSRs associated with L-OHP in our institution, and evaluated the degree to which its occurrence is dependent upon the cumulative dose of L-OHP in patients who had an interruption of L-OHP. Results: Within the sample of 54 patients, HSRs occurred after a median treatment course number of 8 (range 2-19), and the median cumulative dose of L-OHP being 700 mg/m2 (range 170-1615). In these subjects, grade1/2/3 HSRs developed in 33/20/1 patients, respectively. Re-challenge of L-OHP combined with prophylactic agents was performed in 42 patients (78%). There were 16 patients who had an L-OHP- free interval, in whom the major reason for L-OHP withdrawal was neurotoxicity, with reintroduction because of tumor progression or recurrence. Of these 16 patients, 10 developed the first HSRs after reintroduction of L-OHP. Among these 10 patients, grade1/2/3 HSRs developed in 6/3/1 patients, respectively, and occurred at a median course number of 2.5 following re-infusion of L-OHP, or 12 treatments after the initial infusion. The median cumulative dose of L-OHP at HSRs in this patient group was 213 mg/m2 after the re-introduced infusion, and a total of 1088 mg/m2 since initial onset of treatment. Conclusions: Our results suggest that the development of HSRs during L-OHP treatment depends on the cumulative dose from the initial administration even in patients who experienced an L-OHP-free interval. No significant financial relationships to disclose.

Familial PSC: A Descriptive Report of Clinical Features of Patients and Relatives

Familial PSC: A Descriptive Report of Clinical Features of Patients and Relatives

TNF-α plays a role in hepatocyte apoptosis in Niemann-Pick type C liver disease

Niemann-Pick type C (NPC) is a fatal autosomal recessive lysosomal storage disease clinically characterized by neurodegeneration and liver disease. Heterogeneous mutations in the NPC1 and NPC2 genes cause impaired egress of free cholesterol from lysosomes, leading to accumulation of cholesterol and glycosphingolipids. Key features of NPC liver disease include hepatic apoptosis, inflammation, and fibrosis. It is unclear what signaling events regulate these disease processes in NPC. We hypothesize that tumor necrosis factor alpha (TNF-alpha), which is involved in both proinflammatory and apoptotic signaling cascades, is a key mediator of inflammation, apoptosis, and fibrosis in NPC liver disease. In this study, we evaluated the role of TNF-alpha signaling in NPC liver disease by utilizing NPC1-specific antisense oligonucleotides to knock down NPC1 expression in control and TNF-alpha knockout mice. In the absence of TNF-alpha, NPC1 knockdown produced liver disease with significantly less inflammation, apoptosis, and fibrosis.

The National Niemann–Pick C1 disease database: Report of clinical features and health problems

Niemann-Pick type C1 (NPC1) disease is an autosomal recessive disorder characterized clinically by neonatal jaundice, hepatosplenomegaly, vertical gaze palsy, ataxia, dystonia, and progressive neurodegeneration. The present study provides basic clinical and health information from the National Niemann-Pick C1 disease database that was obtained using a clinical questionnaire of 83 questions mailed to families affected by NPC1 disease living in the United States. The study was conducted over a 1-year period, during which time parents/caregivers and physicians completed the clinical questionnaire. Sixty-four percent (87/136) of the questionnaires were returned, with 53% and 47% representing male and female NPC1 patients, respectively. The average age of diagnosis for NPC1 disease was 10.4 years, with one-half of patients being diagnosed before the age of 6.9 years. The average age of death for NPC1 disease was 16.2 years, with one-half of patients dying before the age of 12.5 years. A common clinical symptom reported at birth was neonatal jaundice (52%), followed by enlargement of the spleen (36%) and liver (31%); ascites (19%) and neonatal hypotonia (6%) were much less frequent. With respect to developmental difficulties, the most common findings included clumsiness (87%), learning difficulties (87%), ataxia (83%), dysphagia (80%), and vertical gaze palsy (81%). Together, these findings confirm and extend previous reports investigating the clinical features associated with NPC1 disease.

Adult peripheral neuroblastoma

Report of clinical features, diagnostic and surgical aspects observed in a case of adult peripheral neuroblastoma infiltrative of the lumbosacral plexuses. The patient, a 39-year-old male, presented with sciatalgia and progressive crural monoplegia. Characteristic histological features of this rare tumor are described. Surgical resection was attempted via a posterior transgluteal approach to the retroperitoneum through the greater sciatic foramen.