No abstract

A polymorphism characterized by the insertion or deletion of a 287-bp Alu repeat sequence in intron 16 of the angiotensin-converting enzyme gene determines about half the serum angiotensin-converting enzyme level variability among individuals. The deletion polymorphism is associated with higher levels of angiotensin-converting enzyme and perhaps with a greater risk of cardiovascular diseases. The relative frequency of this genetic polymorphism in different ethnic groups is not known. The objective of this study was to compare the frequency of angiotensin-converting enzyme gene insertion/deletion polymorphism in different ethnic groups. Angiotensin-converting enzyme genotype was determined in middle-aged healthy hospital workers of three different ethnic origins (African Americans, whites, and Indians). There were 142 African Americans, 136 Indians, and 82 whites. The distribution of the deletion-deletion, insertion-deletion, and insertion-insertion genotypes in African Americans (29%, 60%, and 11%, respectively), Indians (19%, 50%, and 31%, respectively) and whites (29%, 40%, and 31%, respectively) was significantly different (p = < 0.005). The frequency of the deletion allele among African Americans, Indians, and whites (0.59, 0.49, and 0.44, respectively) was also significantly different (p=0.05). African Americans had the highest frequency of deletion allele and the lowest frequency of the insertion-insertion genotype among the three groups. The frequency of the deletion polymorphism of the angiotensin-converting enzyme gene is different among African Americans, whites, and Indians. This may be important in relation to the high risk of cardiovascular morbidity and mortality in African Americans and may be relevant in explaining differences in cardiovascular diseases in different populations. This finding also emphasizes the importance of studying angiotensin-converting enzyme gene polymorphism in genetically homogenous populations. Because of the small size of this study, however, these findings need further confirmation.

Statewide newborn screening for Pompe disease began in Illinois in 2015. As of 30 September 2019, a total of 684,290 infants had been screened and 395 infants (0.06%) were screen positive. A total of 29 cases of Pompe disease were identified (3 infantile, 26 late-onset). While many of the remainder were found to have normal alpha-glucosidase activity on the follow-up testing (234 of 395), other findings included 62 carriers, 39 infants with pseudodeficiency, and eight infants who could not be given a definitive diagnosis due to inconclusive follow-up testing.

X-linked adrenoleukodystrophy (X-ALD) is a genetic neurodegenerative disorder with an approximate incidence of 1 in 14,700 births. Both males and females are affected. Approximately one-third of affected males develop childhood cerebral adrenoleukodystrophy, which progresses rapidly to severe disability and death. In these cases, early surveillance and treatment can be lifesaving, but only if initiated before the onset of neurologic symptoms. Therefore, X-ALD was added to the Recommended Uniform Screening Panel. We report outcomes of the initial screening of approximately 276,000 newborns in Illinois. The lipid C26:0 lysophosphatidylcholine (C26:0-LPC) was measured in dried blood spots (DBS) using liquid chromatography with tandem mass spectrometry. Results ≥ 0.28 µmol/L were considered screen positive. Of 18 screen positive results detected, 12 cases were confirmed. Results were reported as borderline if initial and repeat analyses were ≥0.18 and <0.28 µmol/L. Of the 73 borderline screen results, 57 were normal after analysis of a second sample. Five X-ALD cases were identified from borderline screens. Newborn screening of X-ALD was successfully implemented in Illinois, and results were comparable to reports from other states. Early identification of infants with this potentially life-threatening disorder will significantly improve outcomes for these children.

All newborn screening (NBS) for mucopolysaccharidosis-I and -II (MPS-I and MPS-II) is carried out via the measurement of α-iduronidase (IDUA) and iduronate-2-sulfatase (IDS) enzymatic activity, respectively, in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and data from recent MPS-II population screenings and studies from the Mayo Clinic show that the false positive rate can be dramatically reduced by the inclusion of a second-tier analysis of glycosaminoglycans (GAGs) in DBS as part of NBS. In the present study, which focused on MPS-II, we obtained newborn DBS from 17 patients with severe MPS-II, 1 with attenuated MPS-II, and 6 patients with various IDS pseudodeficiencies. These samples were submitted to two different GAG mass spectrometry analyses in a comparative study: (1) internal disaccharide biomarkers and (2) endogenous biomarkers. For both of these methods, the biomarker levels in six patients with pseudodeficiencies were below the range measured in MPS-II patients. One patient with attenuated MPS-II was not distinguishable from severe disease patients, but all MPS-II patients were distinguishable from the reference range using both methods. The minimal differential factor (lowest GAG marker level in MPS-II samples divided by highest level in the reference range of 60 random newborns) was 3.01-fold for the internal disaccharide method. The endogenous biomarker method demonstrated an improved minimum differential of 5.41-fold. The minimum differential factors between MPS-II patients and patients with pseudodeficiencies for the internal disaccharide and endogenous biomarker methods were 3.77-fold and 2.06-fold, respectively. This study supports use of the second-tier GAG analysis of newborn DBS, especially the endogenous disaccharide method, as part of NBS to reduce the false positive rate.