Linked Life Data

2235122

Source:http://linkedlifedata.com/resource/pubmed/id/2235122

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1990-12-7
pubmed:abstractText
Evidence is emerging that primary systemic carnitine deficiency, a potentially lethal but eminently treatable inborn error of fatty acid oxidation, involves a cellular defect in the uptake of carnitine. We present four unrelated children with primary carnitine-responsive cardiomyopathy, weakness (with or without hypoketotic hypoglycemic encephalopathy), low serum and/or tissue carnitine concentrations, and severe renal carnitine leak. Dicarboxylic acids were absent in the urine of three children who were tested, and all four had a rapid and dramatic improvement in cardiac function, strength, and somatic growth after carnitine therapy. We studied carnitine uptake in cultured skin fibroblasts from all four children and seven of the eight healthy nonconsanguinous parents. [3H]L-carnitine uptake was evaluated in vitro under linear time kinetics. Substrate concentrations were varied from 0.1 to 1000 microM. Physiologic uptake was determined at carnitine concentrations between 0.1 and 50 microM. Nonspecific uptake was determined at a concentration of 10 mM. The four patients had negligible uptake throughout the physiologic range, implying a marked deficiency in the specific high-affinity, low-concentration, carrier-mediated uptake mechanism. At a concentration of 5 mumol/L, the mean velocity of uptake in the four patients was 2% of control values. Their parents showed intermediate maximal rates of carnitine uptake ranging from 13 to 44% of control Vmax values, but normal Km values, suggesting that the heterozygotes had a reduced number of normal functioning carnitine transporters. The observed reduction in Vmax values for the parents supports an autosomal recessive inheritance pattern and may be a more sensitive indicator of heterozygosity than serum carnitine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0031-3998
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
247-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy.
pubmed:affiliation
Division of Pediatric Neurology, Columbia University, New York, New York 10032.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Case Reports, Research Support, Non-U.S. Gov't