John Menkes, 79; neurologist identified congenital disorders

LOS ANGELES - Dr. John H. Menkes, a pediatric neurologist who identified Menkes disease, maple-syrup urine disease, and other congenital disorders of the neural system, died Nov. 22 at Cedars-Sinai Medical Center of complications from cancer. He was 79.

Later in his career, Dr. Menkes was as an expert witness for the plaintiffs in a number of trials involving damage caused by vaccines, wrote three novels, and wrote three plays that were produced in Los Angeles, one of which, a Holocaust drama, "The Last Inquisitor," won the prestigious Drama-Logue Award.

"He was a true pioneer in the field," said Raman Sankar, chief of pediatric neurology at University of California at Los Angeles. "He was one of the giants."

In 1951, Dr. Menkes was an intern at Boston Children's Hospital when he encountered a newborn who was drowsy and failed to take formula. The infant had been diagnosed with kernicterus, a form of brain damage caused by jaundice.

In talking to the mother, Dr. Menkes learned that the urine of two earlier children who had died had an unusual odor, while that of a daughter who lived did not. By the infant's third day, its odor and perspiration had also begun to smell strange.

"I am sure that I must have asked nearly everyone at the hospital but could get no better answer than that it smelled like maple syrup," Dr. Menkes later wrote. "After all, we were in New England."

Dr. Menkes prepared the first thorough description of the disorder but did not have enough urine to isolate the chemical responsible. Several years later, while on a fellowship at the New York Neurological Institute, he obtained another sample of the urine. He isolated abnormally high quantities of branched-chain amino acids that were responsible for the odor.

Eventually, it was shown that the disorder, which affects 1 in 180,000 babies - but has a higher incidence in Amish and Mennonite communities - is caused by an enzyme defect that prevents normal breakdown of amino acids.

During his residency at Johns Hopkins University School of Medicine, Dr. Menkes came upon another infant who had appeared normal at birth but later developed floppy muscle tone, seizures, and failure to thrive, among other symptoms. The boy also had coarse, brittle hair.

Dr. Menkes was the first to describe the syndrome, which affects about 1 in 250,000 infants. Researchers later discovered it is caused by a defective enzyme on the X- chromosome that interferes with the metabolism of copper. The disorder is now called "kinky hair syndrome" or Menkes disease.

Because of his identification of congenital disorders, Dr. Menkes was approached by a publisher interested in a pediatric neurology textbook that focused on new developments in the neurosciences. "Textbook of Child Neurology," first published in 1974, became the standard textbook worldwide in the field.