Evidence for Linkage of Human Primary Systemic Carnitine Deficiency with D5S436: A Novel Gene Locus on Chromosome 5q

SummaryPrimary systemic carnitine deficiency (SCD) is a rare hereditary disorder transmitted by an autosomal recessive mode of inheritance. The disorder includes cardiomyopathy, muscle weakness, hypoketotic coma with hypoglycemia, and hyperammonemia. In this study, we conducted a linkage analysis of a Japanese SCD family with a proband—a 9-year-old girl—and 26 members. The serum and urinary carnitine levels were determined for all members. The entire genome was searched for linkage to the gene locus for SCD, by use of a total of ∼300 polymorphic markers located ∼15–20 cM apart. In the family, there were two significantly different phenotypes, in terms of serum free-carnitine levels: low serum free-carnitine level (29.5±5.0 μM; n=14) and normal serum free-carnitine level (46.8±6.2 μM; n=12). There was no correlation of urinary free-carnitine levels with the low serum-level phenotype (putative heterozygote), but in normal phenotypes (wild type) urinary levels decreased as the serum levels decreased; renal resorption of free carnitine appeared to be complete in wild-type individuals, when the serum free-carnitine level was