The F+F test is characterized by an excellent sensitivity and negative predictive value, and the diagnosis of incomplete dRTA can be excluded reliably in a patient who acidifies their urine normally with this test. However, its lack of specificity is a drawback, and if there is any doubt, an abnormal F+F test may need to be confirmed by a follow-up NHCl test. Ideally, a prospective blinded study in unselected KSFs is needed to accurately assess the reliability of the F+F test in diagnosing, rather than excluding, dRTA.

A novel sequence change in repeat 3 of the promoter of the low-density lipoprotein receptor (LDLR) gene, À139C4G, has been identified in a patient with familial hypercholesterolemia (FH). LDLR -139G has been passed to one offspring who also shows an FH phenotype. Transient transfection studies using luciferase gene reporter assays revealed a considerable reduction (7471.4% SEM) in reporter gene expression from the À139G variant sequence compared to the wild-type sequence, strongly suggesting that this change is the basis for FH in these patients. Analysis using electrophoretic mobility shift assay demonstrated the loss of Sp1 binding to the variant sequence in vitro, explaining the reduction of transcription.

No abstract