Dr. House of TV fame was not available, so I was called into consultation for this 24 day old female Jewish infant. She had been hospitalized and seen by other physicians previously. Shortly after birth, when the baby was fed, she gagged and became agitated. Because of the suspicion of sepsis at this young age, intravenous antibiotics were initiated. After 48 hours, however, the cultures were negative and the antibiotics were discontinued. Feeding was re-attempted, but the baby began vomiting and gagging again on the sixth day of life. She was re-admitted to the hospital, where abdominal x-rays were reported normal with no sign of obstruction or infection and a scan of the brain was also normal. Gastrointestinal (GI) and cardiology consults were requested. The GI specialist diagnosed reflux and the cardiologist, after performing an echocardiogram and an EKG, reported that there were no heart abnormalities. The doctors diagnosed her as “failure to thrive”.
When I interviewed the mother, I learned that the baby sustained second degree burns on her back and legs first noticed during her previous hospital admission. The doctors felt that a heating blanket probably malfunctioned and overheated and caused the burn. On my examination, the baby’s lower left back showed a scar which was slightly red and well healed, consistent with the history of the second-degree burn. A neurological exam revealed generalized hypotonia (decreased muscle tone) and also an absence of the deep tendon reflexes, which is the response elicited when your doctor hits your knee with a reflex hammer. Additionally, her tongue was unusually smooth.
There are about a dozen disorders that could lead to absent or decreased reflexes in childhood. One of them which affect persons of Ashkenazi Jewish descent and which presents in infancy is known as familial dysautonomia (Riley-Day Syndrome). The incidence of this autosomal recessive disorder is about 1 in 3,600 live births and approximately 1 in 30 persons is a carrier. The defective gene has been mapped to the 9q31-33 locus.
Patients with this disorder have abnormal or reduced numbers of nerve fibers that usually carry pain, temperature and taste sensations. They also have a smooth tongue. Infants with familial dysautonomia present with poor sucking and swallowing, occasional vomiting and aspiration pneumonia. Breath-holding spells are common, followed by fainting and cyanosis, and various neurological defects. Walking is delayed and clumsy, probably because of poor sensory feedback from muscle spindles. Of significance is that when these children cry, tears are absent. Seizures are also common.
There are many specific tests to help make the diagnosis, including Amniocentesis. Genetic counseling is readily available for patients and their families.
Currently, treatment is symptomatic with certain medications that control temperature and blood pressure as well as seizures
Because of better therapy, over 40% of surviving patients are over 20 years of age. It still remains, however, a progressive and life-threatening disorder. Genetic treatment is not yet available but there are many clinical trials currently underway to correct the underlying abnormality.
In the meantime, however, Dr. Lorenz Studer from Sloan-Kettering in New York recently extracted reprogrammed or induced pluripotential cells (able to become any cell type in the adult body) from patients with familial dysautonomia and grew them in the laboratory in Petri dishes, which recapitulated the abnormalities seen in the patients. Now the doctor can experiment with medications and other therapies in an attempt to cure the disease without harming the patient.
My patient most likely developed second-degree burns on the heating blanket because she did not feel pain when the burn began and did not cry to alert the nurses or her mother that something was wrong. Her poor feeding, sucking and swallowing, along with her bouts of vomiting, were not signs of infection but rather a familial dysautonomia. The absent reflexes and the smooth tongue, along with her Ashkenazi Jewish background, were practically diagnostic for this syndrome.
My patient is now 14 years of age and walks slowly and somewhat unsteadily. She has had numerous hospitalizations for pneumonia and fractures, and she takes seizure and blood pressure medications daily. Unfortunately, she is exclusively fed through a tube that goes into her stomach (gastrostomy tube), but she is almost always in good spirits, and she is the only grandchild who calls her lonely grandmother daily.
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May 3, 2010 | 2:16 pm
At the present time and for many millennia before, we physicians wait for people to get sick, and then we treat them with medication, surgery and other therapies. But once we can construct a profile of every person’s genetic predisposition to disease, medicine will finally become predictive and preventive. We are at the dawn of a new genetics—a paradigm shift from treatment to prevention, which is a result of the Human Genome Project (a 15-year, $3 billion quest), which maps every gene and discovers markers for hereditary disorders. In the coming years, as medical researchers discover the molecular causes of various diseases, novel preventive strategies, new drugs, and eventually gene therapy will change the face of medicine.
From the beginning of recorded history, humans have been intrigued by physical traits that run in families for generations – certain facial features, eye color, hair color, and various deformities. Before the first scientific law of genetics was described by Gregor Mendel in 1865, ancient civilizations recognized the basic principles of heredity and used it in breeding animals and plants to improve their characteristics.
The Talmud (ancient Hebrew compendium of civil and criminal law) is generally not thought of as a medical textbook or a treatise on genetics, but this brilliant tome insightfully incorporated a provision that exempts a Jewish boy from circumcision if a maternal uncle (not a paternal one) is a hemophiliac (a person who bleeds excessively because of the absence of clotting factors). This exception reveals a profound understanding by the sages of the Talmud on inheritance.
There are many types of hemophilia, with a higher number of the Type C (deficiency of factor XI) found in Ashkenazi Jews. Clotting factor defects are genetic and genes determine everything physical about a person, including these factors. A baby receives half of its genetic information from its mother (through the egg cell) and half from the father (through the sperm cell). If the mother or father has the hemophilic gene, it may be passed to the baby through the egg or sperm. Hemophilia C can affect both sexes and is autosomal in inheritance as the gene for factor XI is located on chromosome 4. There are currently several treatments available to prevent bleeding in hemophiliacs, but gene therapy is on the horizon. Basically, a healthy version of the defective blood factor gene is inserted into the hemophilic, which hopefully will change their genetic makeup, permitting them to produce normal amounts of clotting factors on their own.
In further articles, I will explore the answers to several questions: “What is a gene?”, “What is a chromosome?”, What is inheritance?”, “If a genetic disorder runs in my family, what are the chances that my children will inherit the condition?”, “What is gene mutation?”, “What is gene therapy?”, “What is gene testing?”, “Will gene testing tell me if I am susceptible to a certain disorder?”, and “What are other genetic disorders that affect Jews?”
Finally, we are exploring the negative implication of gene defects on the Jewish people, but we should not forget the overwhelming positive aspects: exemplary scientists, rabbis, writers, lawyers, doctors, nurses, businessmen, teachers, professors, and many, many Nobel Laureates.