Elevated catecholamine metabolites in patients with Costello syndrome.
Costello syndrome is a rare congenital anomaly syndrome with a predisposition to specific tumors, including neuroblastoma, rhabdomyosarcoma, and transitional cell carcinoma of the bladder. The increased risk for solid tumors led to the proposal of a tumor screening protocol. A screening test for neuroblastoma consists of measuring catecholamine metabolites in urine, an assay that may also be used for diagnostic confirmation of a suspected catecholamine secreting tumor. We report eight patients with Costello syndrome with elevated catecholamine metabolites, vanillylmandelic acid (VMA) and/or homovanillic acid (HVA), in urine. Each patient had additional laboratory and/or imaging studies. None of the patients was found to have a neuroblastoma or another catecholamine secreting tumor. In two cases, the assays were performed because the patients were symptomatic with diaphoresis and hypertension, respectively, and in the other six cases the assays were performed in order to screen for neuroblastoma. The pathophysiology for the catecholamine metabolite abnormality in these patients with Costello syndrome remains unclear. However, it appears that in this patient group an elevation above the normal limit, defined as 2 standard deviations (SD) above the mean for age, is more likely to be a variant, rather than a sign of a neuroblastoma. Thus, it may be prudent not to use this assay as a screening test, and to take the frequently elevated results into consideration when interpreting diagnostic assays.
Gripp
Karen W
KW
Division of Medical Genetics, A. I. duPont Hospital for Children, PO Box 269, Wilmington, DE 19899, USA. kgripp@nemours.org
Kawame
Hiroshi
H
Viskochil
David H
DH
Nicholson
Linda
L
D000015:Abnormalities, Multiple / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006719:Homovanillic Acid / Q000652:urine*; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D014642:Vanilmandelic Acid / Q000652:urine*
D015415:Biomarkers; D014642:Vanilmandelic Acid; D006719:Homovanillic Acid