Conservatives’ deep-seated suspicion of the United Nations was on high display in the Senate Tuesday, when Republicans blocked ratification of a U.N. treaty aimed at ending discrimination against the disabled despite assurances it wouldn’t affect U.S. sovereignty.

Supporters of the Convention on the Rights of Persons With Disabilities say the treaty — based in part on the landmark Americans With Disabilities Act of 1990 — is non-binding and wouldn’t change or challenge U.S. law.

But conservative groups — who long have considered the U.N. a threat to U.S. self-rule — weren’t convinced the committee created by the treaty to promote the rights of disabled people globally has only an advisory role, and campaigned hard against it.

“The U.S. Congress, American civil society and special interest groups are far better positioned to conduct such reviews than a committee of disability experts from Bangladesh, China, Qatar and Tunisia, which are current members of the [treaty] committee,” said Steven Groves, who heads the Heritage Foundation’s Freedom Project.

The Family Research Council said the complex treaty would open a Pandora’s box of legal headaches for the U.S. “This is a treaty with 50 Articles, and anyone who suggests … that it doesn’t require ‘one change to U.S. law’ must be waiting to pass it to find out what’s in it,” said a statement on the group’s website after the vote.

Thirty-eight Republicans appear to have agreed and voted Tuesday to reject the treaty. And while 61 senators supported it — including eight Republicans and two independents — the tally fell five votes short of the two-thirds majority needed to pass. No Democrat voted against it. Sen. Mark Kirk, Illinois Republican, was absent and did not vote.

The U.N. adopted the treaty in 2006. President Obama agreed to it in 2009, though it failed to move through the Senate — which must ratify all treaties — until this year. It has been signed by 154 nations and ratified by 126.

Sen. Mike Lee, a Utah Republican and a leading treaty opponent, said similar U.N. treaties have forced demands on national governments that fall outside their legal, economic and cultural traditions.

The senator said he particularly was worried U.S. parents could be denied the right to home-school a child with disabilities if the U.N. committee — or another body carrying out its recommendations — determined it would be in the best interests of the child.

He added the Senate’s action “halted our possible descent down the rabbit hole of international ‘entitlement rights’ which could have serious consequences for domestic law.”

“I applaud the Senate for preserving our sovereignty,” he said.

But treaty supporters say its aim is to improve conditions for the disabled throughout the world, not the United States. Ratifying the document, they say, would “export” the key American value that all persons, regardless of ability or disability, should be treated fairly and with respect.

“This treaty is not about America, it’s about America changing the world,” said Sen. John F. Kerry, Massachusetts Democrat, who is Senate Foreign Relations Committee chairman and a leading supporter of the treaty.

Mr. Kerry called Tuesday was “one of the saddest days I’ve seen in almost 28 years in the Senate.”

Former GOP Sen. Bob Dole, a wounded World War II veteran and prime sponsor of the original ADA law who supports the treaty, made a rare visit to the Senate floor to watch the debate and vote.

Senate Majority Leader Harry Reid, Nevada Democrat, chastised the treaty’s opponents, saying “their arguments against the treaty had no basis in fact” and that it “does not change United States law.”

Mr. Reid has vowed to bring the measure up for another vote in the upcoming 113th Congress, which convenes next month. But while the Senate’s Democratic majority will grow by two next year, three Republicans who supported the treaty are leaving office in January, offering little hope it will be successful the next go-around.

The Senate’s treatment of measure also means Mr. Reid will have little hope to advance more controversial treaties, such as the U.N.’s Law of the Sea Treaty, which establishes international laws governing the maritime rights of countries. It entered into force in 1994 and has been ratified by more than 160 countries.

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