US 11,674,948 B2
Methods and systems for determining autism spectrum disorder risk
Ute Geigenmuller, Lexington, MA (US); Doris Damian, Lexington, MA (US); Maciej Pacula, Lexington, MA (US); Mark A. DePristo, Lexington, MA (US); and Jeffrey R. Luber, Lexington, MA (US)
Assigned to Laboratory Corporation of America Holdings, Burlington, NC (US)
Filed by Laboratory Corporation of America Holdings, Burlington, NC (US)
Filed on Aug. 6, 2018, as Appl. No. 16/55,966.
Application 14/866,791 is a division of application No. 14/493,141, filed on Sep. 22, 2014, abandoned.
Application 16/055,966 is a continuation of application No. 14/866,791, filed on Sep. 25, 2015, granted, now 10,041,932.
Claims priority of provisional application 62/002,169, filed on May 22, 2014.
Claims priority of provisional application 61/978,773, filed on Apr. 11, 2014.
Prior Publication US 2018/0348199 A1, Dec. 6, 2018
Int. Cl. G01N 33/49 (2006.01); G01N 33/68 (2006.01); G16H 50/30 (2018.01); G16H 50/20 (2018.01); G16Z 99/00 (2019.01)
CPC G01N 33/492 (2013.01) [G01N 33/6896 (2013.01); G16H 50/20 (2018.01); G16H 50/30 (2018.01); G16Z 99/00 (2019.02); G01N 2800/28 (2013.01); G01N 2800/38 (2013.01)] 17 Claims
 
1. A method of differentiating between autism spectrum disorder (ASD) and non-ASD developmental delay (DD) in a subject, the method comprising:
(i) measuring levels of a plurality of metabolites in a sample obtained from the subject, wherein the plurality of metabolites comprise hydroxychlorothalonil and a second metabolite,
(ii) determining the hydroxychlorothalonil level in the sample is within an ASD tail effect with a right tail if the level of hydroxychlorothalonil in the sample is greater than 2.645 ng/ml, and
determining the second metabolite level in the sample is within an ASD tail effect,
wherein the second metabolite is selected from the group consisting of: 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF), 3-indoxyl sulfate, 4-ethylphenyl sulfate, 5-hydroxyindoleacetate, 8-hydroxyoctanoate, gamma-CEHC, hydroxyisovaleroylcarnitine (C5), indoleacetate, isovalerylglycine, lactate, N1-Methyl-2-pyridone-5-carboxamide, p-cresol sulfate, pantothenate (Vitamin B5), phenylacetylglutamine, pipecolate, xanthine, octenoylcarnitine, and 1,5-anhydroglucitol (1,5-AG);
wherein the level of 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) is less than 0.396 ng/ml,
wherein the level of 3-indoxyl sulfate is less than 0.584 ng/ml,
wherein the level of 4-ethylphenyl sulfate is less than 0.281 ng/ml,
wherein the level of 5-hydroxyindoleacetate is greater than 2.027 ng/ml,
wherein the level of 8-hydroxyoctanoate is less than 0.711 ng/ml,
wherein the level of gamma-CEHC is less than 0.505 ng/ml,
wherein the level of hydroxyisovaleroylcarnitine (C5) is less than 0.619 ng/ml,
wherein the level of indoleacetate is less than 0.707 ng/ml,
wherein the level of isovalerylglycine is less than 0.438 ng/ml,
wherein the level of lactate is greater than 1.288 ng/ml,
wherein the level of N1-Methyl-2-pyridone-5-carboxamide is less than 0.554 ng/ml,
wherein the level of p-cresol sulfate is less than 0.378 ng/ml,
wherein the level of pantothenate (Vitamin B5) is great than 1.980 ng/ml,
wherein the level of phenylacetylglutamine is less than 0.498 ng/ml,
wherein the level of pipecolate is greater than 1.711 ng/ml,
wherein the level of xanthine is greater than 1.507 ng/ml,
wherein the level of octenoylcarnitine is less than 0.479 ng/ml, and
wherein the level of 1,5-anhydroglucitol (1,5-AG) is less than 0.680 ng/ml;
iii) determining the subject has ASD and not DD based on the identified ASD tails as determined in step (i) and step (ii).