Evaluation and long-term follow-up of infants with inborn errors of metabolism identified in an expanded screening programme
Highlights
► This is the first study on expanded newborn screening results in Spain. ► The use of urine samples adds an important value to the newborn screening. ► Early treatment of inborn errors of intermediary metabolism improves the prognosis.
Introduction
Most cases of inborn errors of metabolism (IEMs) occurring with clinical symptoms result in serious consequences to the affected infants, including mild to severe irreversible mental retardation, lifelong disability, physical handicaps, coma, and early death [1]. These effects can be prevented or significantly reduced in many cases if the IEM is diagnosed early: as a public health measure, newborn screening (NBS) has proved to be diagnostically effective and economically efficient.
As new technologies have emerged, public health authorities have incorporated them in expanded NBS programmes. In particular, tandem mass spectrometry (MS/MS) has gradually been adopted by many countries following the work of Millington et al. [2]. In a single 2–3 minute test, MS/MS can determine over 30 analytes in blood samples impregnated in paper, including amino acids and acylcarnitines. Consequently, it allows the detection of many inborn errors of intermediary metabolism, such as aminoacidopathies, galactosaemia (by measurement of hexose monophosphate [3]), organic acidurias, and disorders related to the oxidation of free fatty acids (FFAs). Otherwise, Pitt et al. reported the first study of urine profiling by MS/MS including a great range of metabolites [4]. Metabolic disorders for which other analytical techniques have been introduced include biotinidase deficiency (BD), screened for by a colorimetric assay [5].
Several studies have examined the long-term outcome and effects of expanded NBS for specific disorders, including classical organic acidurias [6], type I glutaric aciduria (GA-1) [7], maple syrup urine disease (MSUD) [8], and medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) [9], [10]. Others, most of them very recent, have investigated the overall impact of expanded NBS programmes, including long-term outcomes [1], [11], [12], [13], [14].
In Galicia (N.W. Spain), where NBS is performed on 99.9% of newborns and has long used both blood and urine samples, an expanded NBS programme incorporating MS/MS was begun in July 2000. In this paper we report follow-up findings of the patients that were referred to clinical unit for diagnosis and treatment from the NBS programme over a period of 10 years. Our programme has the peculiarity of receiving blood and urine samples simultaneously of all newborns. This is the first such study concerning an expanded screening programme in Spain.
Section snippets
Patients and methods
In our NBS programme, all newborns with abnormal NBS results suggestive of IEMs are referred for evaluation in the Diagnosis and Treatment of Congenital Metabolic Disease Unit of the University Clinical Hospital, Santiago de Compostela (henceforth “the clinical unit”), regardless of whether they present clinical symptoms. Included in this study were all those so referred from the NBS programme between July 1, 2000 and July 1, 2010. Only patients referred from the NBS programme were included.
Results
In Galicia, NBS programme is carried out in 99.9% of all newborns; this represents 4.44% coverage for newborns in Spain. During the study period we identified 137 cases of IEM as a direct result of screening 210,165 newborns, i.e. one case per 2060 newborns if the 35 cases of benign HPA are ignored. For each IEM detected, Table 1 lists the proportion of newborns in which it was detected together with data on the corresponding biochemical marker and on the patients' situation at diagnosis and at
Discussion
In our community, IEMs other than benign HPA, have been diagnosed in 1/2060 newborns as a direct result of screening by our current NBS programme, which basically seeks the abnormalities for which screening is recommended by the American College of Medical Genetics [20], plus cystinuria and GALK. The metabolic disorders most commonly screened for (amino acid disorders other than benign HPA, fatty acid disorders, organic acidurias and urea cycle disorders) were detected through NBS in 1/2960
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