Appropriateness of newborn screening for classic galactosaemia: a systematic review

Abstract

Currently, there is no universal agreement on galactosaemia screening, fundamentally because of the risk-benefit uncertainties. We conducted two exhaustive systematic searches in the main electronic databases (PubMed, Embase, Cochrane, etc.) to recover relevant information about the disease and screening test/s in order to support decision making in Spain. All of the 45 studies identified that covered disease issues were retrospective case series or cross-sectional analysis (level-4 evidence). Studies consistently found that the majority of patients presented characteristic symptomatology before diagnosis. Long term disabilities were not significantly correlated with age of diagnosis, onset of dietary restriction or strict diet compliance. The five studies that provided accuracy data used different cut-off points and verification tests, and thus differed in their definitions of a positive case (level-3b evidence). The estimated sensitivity was 100 % and the specificity 99.9 %. The false-positive rate ranged from 0.0005 % to 0.25 %, and the PPV from 0 % to 64.3 %. The comparative clinical effectiveness in relation to not screening or implementation of other programs is unknown. In summary, existing evidence remains insufficient to establish the appropriateness of newborn screening for galactosaemia screening, although health benefits could be expected if early diagnosis and treatment is achieved. If screening is implemented in Spain, it would be important that a pilot programme be implemented to assess false positive rate and ensure that early diagnosis is not delayed.

Класична Галактоземія: Особливості Діагностики Та Лікування

“…Виражений генетичний і клінічний поліморфізм КГ, неспеци-фічні симптоми дебюту захворювання, його ранній початок, висока смертність немовлят за відсутності своєчасної дієтотерапії потребують вирішення цілої низки нагальних питань [16,17].…”

“…Проте ранній дебют захворювання ви-магає організації масового неонатального скринінгу, оскільки лікування необхідно розпочинати до кінця першого тижня життя немовляти. Хоча в де яких кра-їнах неонатальний скринінг через пропущені випад-ки захворювання вважають неефективним [16], але в цілому відзначають доцільність його проведення [17].…”

Including Classical Galactosaemia in the Expanded Newborn Screening Panel Using Tandem Mass Spectrometry for Galactose-1-Phosphate

“…Although the precise mechanism of the disease is not fully understood, it typically presents with cataracts, liver failure and a propensity for E. coli sepsis. The incidence of classical galactosemia is reported to be 1:30,000 to 1:100,000 live births depending on the population studied [1][2][3]. The condition is notably prevalent in the traveler population of Ireland with an incidence of 1:430 [4].…”

“…The first is the long-term outcome including issues concerning cognitive decline and neurological manifestations. Among those that develop these symptoms, there is no evidence that the long-term outcome is improved by detecting the disease before the presentation of clinical symptoms [2]. However, some patients do not develop such symptoms.…”

“…The second issue is the poor screening performance that has been observed in many programs. The positive predictive value (PPV) of the current tests in use has been reported to be between 0.9% to 64.3% (average 8.1%) [2]. The large number of false positives are a burden for the health care system and for the families that must undergo further investigation [2,6].…”