Hyperhydroxyprolinaemia detected in newborn screening with tandem mass spectrometry

Abstract

Hydroxyproline has the same integer molecular weight as leucine and isoleucine and is quantified with these by tandem mass spectrometry. An infant was diagnosed with hyperhydroxyprolinaemia following further evaluation of an elevated "leucine" level in newborn screening by tandem mass spectrometry.

Recall rate and positive predictive value of MSUD screening is not influenced by hydroxyproline

“…Lately, another problem has emerged. Two patients with hyperhydroxyprolinemia have been identified by MS/ MS-based NBS for MSUD [1,7]. It has been generally accepted for the last few decades that hyperhydroxyprolinemia is an apparently harmless familial condition which should be categorized as a "non-disease" [6,10,11].…”

“…Hydroxyproline concentration in immature and mature newborns have been reported to range from trace amounts to 75 μmol/L and in subjects with hyperhydroxyprolinemia from 150 to 500 μmol/L [1,2,7]. With a recovery of only 30%, even subjects with the extremely rare condition of hydroxypro- linemia are very unlikely to be detected by NBS for MSUD.…”

Newborn screening for inborn errors of metabolism and endocrinopathies: an update

“…Despite the fact that, for decades, hydroxyprolinemia has been regarded as a harmless biochemical abnormality [82,83], recently two new "patients" have been reported; these were detected by TMS newborn screening [84,195]. Clearly, such elevated hydroxyproline levels should not be reported.…”

A Rapid and Sensitive UPLC-MS/MS-Method for the Separation and Quantification of Branched-Chain Amino Acids from Dried Blood Samples of Patients with Maple Syrup Urine Disease (MSUD)

“…The positive effect of early detection, especially of the severe cases, is well documented [7]; however, NBS results cannot discriminate between severe and milder forms [8]. There are also rare cases of hyperhydroxyprolinemia resulting in a false-positive MSUD screening result [9,10], but this seems to be a minor problem in general [4]. Several methods have been published for second-tier measurement of alloisoleucine [11][12][13], which all use a second extraction from the initial NBS blood spot and chromatographic separation of the isobaric amino acids leucine, isoleucine, and alloisoleucine.…”