Severe perinatal liver disease and down syndrome: An apparent relationship

Ruchelli, Eduardo D.; Uri, Antonia; Dimmick, James E.; Bove, Kevin E.; Huff, Dale S.; Duncan, Lyn M.; Jennings, Jane B.; Witzleben, C. L.

doi:10.1016/0046-8177(91)90111-2

Cited by 97 publications

(68 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4 DS neonates, especially those with TMD, frequently have liver dysfunction. 21,22 However, as all our subjects showed a normal range of aminotransferase, decreased TPO production was unlikely to explain the suboptimal TPO response to thrombocytopenia. With complicated delivery or neonatal asphyxia, reduced platelet counts have been shown in non-DS neonates.…”

Section: Discussionmentioning

confidence: 99%

Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

et al. 2009

View full text Add to dashboard Cite

Background: The pathogenesis of thrombocytopenia during the neonatal period in Down's syndrome (DS) infants remains unclear.Objective: To elucidate kinetic changes of serum thrombopoietin (TPO) level and platelet count, and their correlation in DS neonates.Study Design: Twelve DS infants (male/female: 7/5, term/late preterm: 10/2) born between 1997 and 2007 were included. Blood samples were serially collected during the neonatal period and serum TPO levels were determined in 44 sera using an enzyme-linked immunosorbent assay.Results: Thrombocytopenia <150 Â 10 9 per liter was observed in seven (58%) patients. In 12 DS patients, the median TPO value showed 2.86 fmol ml -1 on day 0, rose to 4.64 fmol ml -1 on day 2, and thereafter decreased to 4.30 fmol ml -1 on day 5, 2.40 fmol ml -1 on days 11-15, and 1.75 fmol ml -1 on days 28-30. This kinetics parallels that in historical non-DS controls. In 35 pair sample analysis from 11 patients without transient myeloproliferative disease, TPO level inversely correlated with platelet count (r ¼ À0.38, P ¼ 0.023). However, there was no significant difference in TPO concentrations between thrombocytopenic and non-thrombocytopenic DS individuals.Conclusions: This is the first study to describe the relationship between TPO level and platelet count in neonates with DS. Median TPO levels and their kinetic changes in DS neonates are comparable to those in non-DS controls. In contrast to earlier findings in several studies showing higher TPO concentrations in thrombocytopenic non-DS newborns than those in non-thrombocytopenic counterparts, the response of the TPO system to thrombocytopenia in DS during the neonatal period seems suboptimal.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

et al. 2009

View full text Add to dashboard Cite

show abstract

“…DS is not usually thought of in association with significant infantile liver disease. However, some reports indicate that children with DS may have severe liver disease at birth or within the first few weeks of life, 34,35 and cirrhosis, granulomas and acidophilic bodies are twice as common among DS patients than control patients. 36 The developmental impairment of the liver observed in trisomic mice may provide the morphofunctional substrate of liver pathology in children with DS.…”

Section: Prominent Proliferation In Peripheral Tissues Of Neonate Andmentioning

confidence: 99%

Early-occurring proliferation defects in peripheral tissues of the Ts65Dn mouse model of Down syndrome are associated with patched1 over expression

Fuchs

Ciani

Guidi

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

Down syndrome (DS) is a genetic pathology due to the triplication of human chromosome 21. In addition to mental retardation, individuals with DS exhibit a large range of variable traits, including co-occurring congenital malformations. It is now clear that neurogenesis impairment underlies the typically reduced brain size and, hence, mental retardation in individuals with DS. The small body size and the constellation of congenital malformations in children with DS suggest that proliferation defects may involve peripheral tissues, in addition to the brain. The goal of the current study was to establish whether a generalized impairment of cell proliferation is a key feature of the trisomic condition. We used the Ts65Dn mouse, a widely used DS model, and examined proliferation in tissues with different embryological origin by 5-bromo-2-deoxyuridine immunohistochemistry. We found that 2-day-old (P2) Ts65Dn mice had notably fewer proliferating cells in the heart and liver, and in all proliferating niches of the skin and intestine. A reduced proliferation rate was still present in the intestine at P15. In all tissues, Ts65Dn mice had a similar number of apoptotic cells as euploid mice, indicating no unbalance in cell death. In the skin, liver and intestine of trisomic mice, we found a higher expression of patched1 (Ptch1), a receptor that represses the mitogenic sonic hedgehog (Shh) pathway. This suggests that Ptch1-dependent inhibition of Shh signaling may underlie proliferation impairment in trisomic peripheral tissues. In agreement with the widespread reduction in proliferation, neonate trisomic mice had a reduced body weight and this defect was still present at 30 days of age. Our findings show that, in all examined peripheral tissues, Ts65Dn mice exhibit a notable reduction in proliferation rate, suggesting that proliferation impairment may be a generalized defect of trisomic precursor cells.

show abstract

“…There have been several reported cases of neonatal cholestasis in Down syndrome associated with bile duct paucity, myeloproliferative disorders and neonatal hemochromatosis. The liver diseases in these cases were fatal [1]. To the best of our knowledge, until now benign neonatal cholestasis associated with Down syndrome has not been reported.…”

Section: Introductionmentioning

confidence: 89%

A Case of Idiopathic Congenital Neonatal Cholestasis in a Patient with Down Syndrome

Huh

Jeong

Park

et al. 2012

Pediatr Gastroenterol Hepatol Nutr

View full text Add to dashboard Cite

Severe perinatal liver disease and down syndrome: An apparent relationship

Cited by 97 publications

References 14 publications

Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

Early-occurring proliferation defects in peripheral tissues of the Ts65Dn mouse model of Down syndrome are associated with patched1 over expression

A Case of Idiopathic Congenital Neonatal Cholestasis in a Patient with Down Syndrome

Contact Info

Product

Resources

About