WASHINGTON (Reuters Life!) - Rare inherited genetic disorders worsened by repeated inbreeding may have brought down the powerful Spanish Habsburg dynasty, Spanish researchers said on Tuesday.
Checks of genealogical charts and analysis of King Charles II's reported health problems suggest he may have had two rare conditions called combined pituitary hormone deficiency and distal renal tubular acidosis, the researchers speculated in the Public Library of Science journal PLoS ONE.
While the occasional marriage of close relative such as first cousins is harmless, repeated intermarriages can make genetic flaws more common, Gonzalo Alvarez and colleagues at the University of Santiago de Compostela reported.
This appears to have happened frequently among the Habsburgs between 1516 and 1700 as they sought to keep power, Alvarez's team said.
"The last king of the Spanish Habsburg dynasty was Charles II. He was physically disabled, mentally retarded and disfigured," they wrote.
"He proved impotent since no children were born from his two marriages. When Charles II died in 1700 the line of the Spanish Habsburgs died with him and a new dynasty -- the French Bourbons -- was installed in Spain."
Their analysis showed nine out of 11 marriages over the 200 years were between first cousins or uncles and nieces.
By looking at the family line of 3,000 relatives of Charles II, they calculated that some members of the dynasty could have 20 percent of their genome being homozygous, meaning they carried two of the same copies of various DNA mutations -- making rare, recessive genetic illnesses more likely.
Then they analyzed accounts of Charles II's various problems. "According to contemporary writings, he was often described as 'big headed' and 'weak breast-fed baby'," they wrote.
"He was unable to speak until the age of 4, and could not walk until the age of 8. He was short, weak and quite lean and thin. He was described as a person showing very little interest in his surroundings (abulic personality)," they added.
"He first marries at 18 and later at 29, leaving no descendency. His first wife talks of his premature ejaculation, while his second spouse complains about his impotency."
He had frequent stomach problems. "He looked like an old person when he was only 30 years old," they added.
All these could be symptoms of an inherited thyroid deficiency, as well as renal tubular acidosis, a type of kidney failure that can cause metabolic problems.
The thyroid is a gland that controls the functions of many other glands and also affects metabolism and development.
"In this way, we may speculate that most of the symptomatology showed by Charles II could be explained by two different genetic disorders," they wrote in their report, published on the Internet at www.plosone.org/.
Reporting by Maggie Fox; editing by Todd Eastham