ABSTRACT
Tandem mass spectrometry (MS/MS) has become a leading technology used in clinical chemistry and has shown to be particularly sensitive and specific when used in newborn screening (NBS) tests. The success of tandem mass spectrometry is due to important advances in hardware, software and clinical applications during the last 25 years. MS/MS permits a very rapid measurement of many metabolites in different biological specimens by using filter paper spots or directly on biological fluids. Its use in NBS give us the chance to identify possible treatable metabolic disorders even when asymptomatic and the benefits gained by this type of screening is now recognized worldwide. Today the use of MS/MS for second-tier tests and confirmatory testing is promising especially in the early detection of new disorders such as some lysosomal storage disorders, ADA and PNP SCIDs, X-adrenoleucodistrophy (X-ALD), Wilson disease, guanidinoacetate methyltransferase deficiency (GAMT), and Duchenne muscular dystrophy. The new challenge for the future will be reducing the false positive rate by using second-tier tests, avoiding false negative results by using new specific biomarkers and introducing new treatable disorders in NBS programs.
Subject(s)
Mass Spectrometry/methods , Neonatal Screening/methods , Tandem Mass Spectrometry/methods , Adrenoleukodystrophy/diagnosis , Adrenoleukodystrophy/prevention & control , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/prevention & control , Guanidinoacetate N-Methyltransferase/deficiency , Hepatolenticular Degeneration/diagnosis , Hepatolenticular Degeneration/prevention & control , Humans , Infant, Newborn , Language Development Disorders/diagnosis , Language Development Disorders/prevention & control , Lysosomal Storage Diseases/diagnosis , Lysosomal Storage Diseases/prevention & control , Movement Disorders/congenital , Movement Disorders/diagnosis , Movement Disorders/prevention & control , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/prevention & controlSubject(s)
Adrenoleukodystrophy/prevention & control , Adrenoleukodystrophy/therapy , Erucic Acids/therapeutic use , Triolein/therapeutic use , Adrenoleukodystrophy/blood , Adrenoleukodystrophy/genetics , Animals , Bone Marrow Transplantation , Child , Drug Combinations , Fatty Acids/blood , Humans , Male , Mice , MutationABSTRACT
X-linked adrenoleukodystrophy (X-ALD) is a sex-linked, inherited, metabolic disorder affecting the nervous system and endocrine organs. At least 20 to 50% of female carriers develop neurological deficits. Identification of female carriers is important, among other reasons because unnecessary new cases of this disorder, which is frequently lethal in boys, can be prevented by prenatal diagnosis. Furthermore, affected male offspring can be screened for adrenocortical insufficiency, which is treatable, or for early signs of cerebral involvement in which case bone marrow transplantation may be considered. Whether or not someone is a carrier can be investigated by determining the concentrations of saturated very-long-chain fatty acids in the plasma or cultured skin fibroblasts, by looking for the presence of X-ALD protein in cultured fibroblasts and by carrying out mutation analysis. Spasticity, painful muscular cramps, lumbago and arthralgias can be treated symptomatically with the same agents used for other aetiologies. A clinical geneticist can provide advice on heredity and the possibilities of prenatal diagnosis and pre-implantation techniques.
Subject(s)
Adrenoleukodystrophy/diagnosis , Adrenoleukodystrophy/genetics , Genetic Carrier Screening/methods , Genetic Testing/methods , Adrenal Insufficiency/etiology , Adrenoleukodystrophy/epidemiology , Adrenoleukodystrophy/prevention & control , Age of Onset , Diagnosis, Differential , Female , Genotype , Humans , Male , Middle Aged , Netherlands/epidemiology , Peroxisomal Disorders/diagnosis , Peroxisomal Disorders/genetics , Peroxisomal Disorders/therapy , Phenotype , PrevalenceABSTRACT
Measurement of plasma very long chain fatty acids is widely recognised as a sensitive screening test for X-linked adrenoleukodystrophy (X-ALD). This test has particular importance because of the highly variable clinical expression of X-ALD. In this affected family the progressive childhood form of X-ALD was accompanied by "non-diagnostic" concentrations of plasma very long chain fatty acids. The implications for diagnosis of X-ALD are discussed.
