Shofar: Ram’s horn sounded during the month of Elul, on Rosh Hashanah and at the close of Yom Kippur, reminiscent of the ram “tangled in the bush by its horns” during the Binding of Isaac (Genesis 22), the shofar sounded at Sinai (Exodus 19) and the shofar of Moshiach (Isaiah 27:13).
My patient, an esteemed Rabbi, recently underwent major abdominal surgery lasting several hours. Within one day postoperatively, he was instructed to blow into a mechanical device to help prevent respiratory complications.
Pulmonary problems are not uncommon after surgery, and they include pneumonia, atelectasis, respiratory failure, prolonged mechanical ventilation, pneumothorax, acute respiratory distress syndrome (ARDS), pleural effusion, and pulmonary embolus.
Atelectasis ( collapse of part or all of the lung) is perhaps the most common, particularly in those patients with neuromuscular or chest wall disease. Because atelectasis in some patients appears to be due to repeated small inspirations, deeper breaths may be helpful. Incentive spirometers encourage expansion of the lungs as much as possible above spontaneous breathing - these have proved to be beneficial in controlled studies.
The Rebbe blew and blew into the spirometer, but his profound weakness precluded successful deep respiratory excursions. Several doctors and nurses hovered over this frail, gentle, brilliant scholar, but could not coax him into breathing deeply. As his attempts increased in frequency, his frustrations grew since he knew failure could possibly transform into pneumonia or atelectasis with their attendant consequences. More importantly, Rosh Hashanah and Yom Kippur were a few days away, and he was emphatic about not missing these High Holy Days; he never missed blowing the shofar during the Days of Awe.
I spoke to the Rebbe. He shared his concerns, his fears, his hopes, but focused on his love for all humanity. He conveyed his dream immediately prior to surgery when he “stood in court and was being judged.” He argued that he is merciful – that he is a good person. Because he is merciful, he wants to help others. He wants to “stay alive to continue to do good things.”
In this same dream, he is moved to another room, surrounded by books, thousands of books that help convey the word of God (this array of books is exactly a replica of every room in his house). He continues to teach: “In Genesis, God blows breath in man.” “He gives him the ‘soul of life’.” “Life is ‘God blowing in and out of man’.”
“I have the answer,” he cries out. “The answer to what?” I asked.
“It is Rosh Hashanah!” he bellows. “I need a Shofar. Bring me a Shofar!”
He put the shofar to his lips, and the wailing sound permeated the hospital corridors. His respirations deepened: full expansion of his lungs was successful. This new “breathing apparatus” may have saved his life. “How do you have the strength?” I asked. He replied, “The shofar is blowing itself.” Days later, he walked unaided to Shul. He stood on the bima, almost glowing, and he blew the shofar better than anyone could imagine. He felt strong. He felt connected to God.
The physical shofar is nothing more than the hollow horn of a ram. When the breath of a human being is blown through it, however, it undergoes a transformation. It becomes a living embodiment of the heart and emotion of the human being expressing the Divine Self, its sense is pulsing within, crying out to its Maker.
The shofar has an aura of awe and holiness about it. Its blasts can shatter hearts of stone and wash away layers of complacency. Its call is capable of bringing us back to places inside ourselves, impenetrable by any other means. The Baal Shem Tov teaches that the shofar is an emotional, intuitive way of gaining access to the deepest recesses of our heart and of divine experiential knowledge. Its blast – a wordless sound – speaks to the heart in a way all the greatest words and insights cannot approach.
May this wonderful Rebbe live a full and healthy life , and continue to blow the Shofar for many more years to come.
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November 3, 2010 | 12:15 am
I asked my patient to comment on his lifelong experience with a genetic disease. He is an extremely bright successful young man who has combated his illness bravely and gallantly. No matter where he is in the world, I will always be available to help him.
—-Norman Lavin, M.D., Ph.D.
As a patient of Dr. Lavin’s, I would like to share my story of living with a Jewish genetic disease. I am an Iranian Jew, and although the genetic conditions prevalent in the Ashkenazi Jewish Community are well known, genetic mutations are not unique to the Ashkenazim (See “Persian Jews and Genetic Diseases”, Jewish Journal Blog, June 6, 2010). The Iranian Jews also have certain genetic predispositions to disease. My condition is known as Autoimmune Polyendocrine Syndrome (APS); it is one of the four diseases prevalent among Iranian Jews. This disease is associated with a genetic mutation in the AIRE gene. The AIRE gene is thought to prevent the immune system from attacking your own body; however a defect in this gene causes the body to recognize certain endocrine glands (hormone producing glands) as foreign and to attack them. Each individual is different in terms of which glands are attacked, however the full disease is usually manifest before the age of 20. In my case, I was first diagnosed with celiac disease when I was 9 years old. I was unable to eat gluten products anymore due to the reaction my body had to gluten. We did not realize then that the Celiac disease was only one part of a more general condition. When I was 16, I became extremely fatigued and experienced constant muscle cramps. Dr. Lavin found that my calcium had dropped to very low levels and diagnosed me with Hypoparathyroidism. Only after this diagnosis did we begin to understand the true nature of my condition. I flew to Denver to visit Dr. George Eisenbath, a specialist in APS, and after genetic testing he determined that I did in fact have the mutation in the AIRE gene that is common to the Iranian Jewish Community.
My experiences have led me to an awareness of some of the deficiencies in today’s standards for Jewish genetic screening. Unfortunately, some of the services that are available for Jewish genetic disease, such as Dor Yeshorim ( an international, confidential genetic screening system used mainly by Orthodox Jews), are strongly geared toward Ashkenazi genetic disease. Smaller Jewish communities are almost ignored by these services. I believe that it is very important to include the entire Jewish community in the services provided. I have also learned that there is a strong stigma associated with genetic disease. Thanks G-d, genetic disease is better understood today and most follow a predictable pattern of inheritance. Unfortunately, it is very difficult for many people to look at these issues objectively rather than viscerally. Much needs to be done in terms of education to increase awareness of the genetic mechanisms of disease onset and inheritance. I hope this forum acts as a portal where people can become more aware of the true nature of genetic disease and I trust that with better public awareness, stigma will gradually dissipate.
October 31, 2010 | 3:46 pm
Aunt Minnie, my mother, and many of their friends played Mahjong every Sunday afternoon for hours upon hours, peppered with sips of coffee, bites of strudel, and soft whispers about Uncle Irving’s ulcer. The game of Mahjong was a favorite amongst Jewish Women, but is also played by millions of people in Asia as well as Asian-Americans. Ruth Unger, president of the New York-based Mahjong League for twenty-six years, states that “you are mixing the tiles and you talk and you talk and these people become your network, your support group – everything you need.”
Mahjong first came to the United States in the 1920s by a man named Joseph Babcock who brought it from Shanghai. The game became very popular and Eddie Cantor, the well-known Broadway star, sang the popular hit: “Since Ma is playing Mahjong”. Mahjong lacked standardized rules, but one Jewish woman changed this by founding the National Mahjong League in 1937 which became the ruling authority, issuing official American rules colloquially known as “Jewish Rules”. It also pledged to devote all of its profits to charity, something that this league continues to do. For example, they supported a pediatric wing at a hospital in Florida and another pediatric wing in the Nassau University Medical Center.
In 2007, The Hong Kong Medical Journal claimed that the game can cause “Mahjong Epilepsy”. Allegedly, twenty-three people in Hong Kong and Taiwan suffered seizures only when playing the tile-clicking game. It is not clear what caused the seizures – perhaps a new competitive spirit or larger bets could have precipitated these events. It is also not clear, since no details are available, that they in fact had authentic seizures. Recently, doctors in the Hunan province of China diagnosed a forty year old woman with a Mahjong- related deep vein thrombosis, which is a dangerous blood clot. These doctors posted a letter in The Lancet Medical Journal which stated that the woman had been sitting for eight hours at a Mahjong game. She had sudden pain in her legs and was brought to the emergency room. Allegedly, she had sat perfectly still while playing the game and had only one soft drink during that entire time. The letter stated that the Mahjong – related deep vein thrombosis initiated by minimal physical movements and dehydration could be complicated by stress and sleep deprivation. The woman spent two weeks in the hospital for this condition receiving intravenous blood thinners while she wore compression stockings. Currently, she has improved significantly and is under- going continuous therapy. It is not clear whether she will ever play Mahjong again.
WHAT IS DEEP VEIN THROMBOSIS (DVT)?
Deep Vein Thrombosis occurs when a blood clot forms in one of the body’s deep veins, usually in the legs. Although serious complications are rare, if left untreated there is a potential that the clot could travel to the lungs, causing a life-threatening condition known as Pulmonary Embolism. Because only 30% of these patients experience symptoms, it can be difficult to recognize.
DEEP VEIN THROMBOSIS RISK FACTORS
There are many reasons why people might develop DVT which include:
1. A history of DVT
2. Certain inherited disorders such as Factor V Leiden
3. Birth Control Pills
4. Injury to a deep vein during surgery
5. Injury to a deep vein secondary to trauma
6. Slow blood flow from lack of movement (after surgery, being bedridden, or sitting for long hours in an airplane or automobile or playing Mahjong)
8. Certain treatments for cancer
9. Central Venous Catheter ( a tube placed in the vein to allow access to the blood stream for medication.).
COULD YOU HAVE DEEP VEIN THROMBOSIS?
1. Have you noticed any swelling in either of your legs, your ankles and feet or
along any vein?
2. Do you experience pain, tenderness or other discomfort in your legs?
3. If you do experience pain in your legs, does it feel like a cramp in your calf and does it become more pronounced when standing or walking?
4. Have you noticed any pain or swelling in your arms or neck?
5. Does there appear to be any unusual redness or warmth in your legs, arms or neck?
If you think you have DVT, call your doctor or go to the emergency room immediately.
In spite of the internet, iPhones, iPads, 3D movies, wonderful restaurants and hundreds of other social activities, the game of Mahjong continues exuberantly amongst the Jewish woman in New York, Miami, Chicago, and Los Angeles. So ladies: don’t get dehydrated, move around frequently and for goodness sakes, place smaller bets.
August 4, 2010 | 2:03 pm
I was raised in a “shtetl” on the west side of Chicago, where communal life was in large measure under the direction of the Jewish Elders. Religiosity dominated our daily life, including our interaction with family and friends. Our community was also concerned about safety and health. Medical care was expensive and generally inaccessible, so most treatment modalities were learned from family and friends. One of these was cod liver oil. With only one exception every year (Yom Kippur), my mother forced down my throat a large tablespoon of the most rancid, smelly oil ever created on this planet. Motor oil would have probably tasted much better. In retrospect, this was clearly done with concern and caring for my health and well-being, which was not obvious while I was belching and retching for an hour after the ingestion of this foul-smelling, fishy oil. It was 30 years later before I ever ate fish again.
Cod liver oil was traditionally manufactured by filling a wooden barrel with fresh cod livers and seawater and allowing the mixture to ferment for up to a year before removing the oil. Unfortunately, I once had a quick glimpse of this process at the rear of a fish market when I was a young child. Aaach! Today, cod liver oil is made by cooking and extracting the liver of this fatty fish during the manufacture of fishmeal. The Jewish mother felt that this therapeutic product could have a positive effect on the health of the heart and the bone, as well as nourishment for the skin, hair and nails. It also helped ease the pain and joint stiffness associated with arthritis, and the use of cod liver oil during pregnancy was associated with a lower risk of type I diabetes in the offspring. In a recent Norwegian study, more than 68,000 female cancer patients who took daily cod liver oil supplements had significantly reduced mortality compared to women who did not take such supplements.
Cod liver oil has been utilized for many centuries. In addition to their diet, the Vikings used this oil as a lubricant to allow the transport of ships across land – the oil was smeared on logs which acted as rollers beneath the hull of the ship.
The ingredients in cod liver oil that are therapeutic include omega-3 fatty acids, vitamin A, and vitamin D. Studies have shown that this product has the potential to reduce both the progression of cardiovascular disease and related mortality, including sudden cardiac death. Researchers also found that people who suffer from depression who received a daily dose of 1 gram of an omega-3 fatty acid (found in cod liver oil) for 12 weeks experienced a decrease in their symptoms, such as anxiety, sadness and sleeping problems.
You now have a choice. You could continue to take the cod liver oil, but now flavored and often in a capsule form, or you could just simply supplement with Vitamin D tablets (and add omega-3 fatty acids). Low vitamin D status is extremely common worldwide because of low dietary intake and low skin production. Suboptimal vitamin D levels contributes to the development of rickets, osteoporosis, falls, fractures and a multitude of other conditions. Although consensus does not exist, it appears that circulating vitamin D levels greater than 30-32 ng/ml are needed for optimal health. To achieve this, daily intake of at least 1000 IU of D3 daily are required, and it is probable that substantially higher amounts are needed to achieve normal values in a population basis. Widespread optimization of Vitamin D status likely will lead to prevention of many diseases with attendant reduction of morbidity, mortality and expense.
LOW VITAMIN D CONSEQUENCES
A. Low vitamin D has long been associated with rickets and has a role in the pathogenesis of osteoporosis by way of calcium malabsorption. Recent studies show that low Vitamin D levels are associated with higher fracture risk. In addition, a dose effect was reported with greater Vitamin D intakes and higher achieved vitamin D concentrations, providing superior fracture reduction benefit. Thus, low vitamin D status leads to adverse bone consequences, which can be corrected with supplementation.
B. Muscle function and falls. Regardless of the mechanism, patients with osteoporosis/osteomalacia because of vitamin D deficiency develop muscle pain and weakness that is improved with vitamin D therapy. Muscle biopsy in such people reveals atrophy of the fast twitch fibers, which may explain the increased fall risk in vitamin D deficient individuals. Vitamin D replacement reduces this risk by more than 20%.
C. Cancer. Vitamin D has antiproliferative and pro-differentiating effects on many cell types, which may reduce cancer risk. Consistent with this, there is a body of literature which states that low vitamin D intake and /or less sunlight exposure leads to an increased risk of mortality from multiple types of cancer. Prospective trials of vitamin D supplementation with cancer as an endpoint are very limited. However, a small prospective study of postmenopausal women found calcium plus vitamin D3 at 1100 IU daily reduces overall cancer risk by approximately 60%. To summarize, observational data in one small randomized trial find low vitamin D status to be associated with higher cancer risk. Additional prospective studies are needed.
D. Other Conditions
1. Immunity. It is likely that vitamin D has immune modulating effects. It has long been recognized that vitamin D deficiency is associated with respiratory infections, which perhaps contributed to the previous use of cod liver oil in anti-tuberculosis therapy. Low vitamin D status is associated with an increased risk of autoimmune and potentially infectious diseases. In addition, inflammation is increasingly becoming recognized as a contributor to the pathogenesis of various diseases, and vitamin D modulates inflammatory cytokine production.
2. Diabetes. It has been suggested that endemic low vitamin D is contributing to the increased prevalence of diabetes mellitus. Multiple potential mechanisms have been proposed, including vitamin D increasing insulin production/secretion. Recent observational studies associate low Vitamin D status with both diabetes type I and type II. Prospective studies of vitamin D supplementation are clearly indicated; it appears that low vitamin D status impairs glucose metabolism.
3. Heart Disease. Observational studies report an association between low vitamin D and cardiovascular disease. Potential mechanisms include a vitamin D effect on theendothelium, vascular smooth muscle, and/or cardiomyocytes – all of which possess the vitamin D receptor. Prospective studies to further evaluate this reported association are needed.
4. Pain and headaches. There are a few journal articles suggesting that vitamin D supplementations may help with headaches.
5. Alzheimer’s and Parkinson’s disease. Some studies have demonstrated a link between
low vitamin D levels and cognitive dysfunction, and a few studies have shown low vitamin D levels to be linked to Parkinson’s disease.
In summary, low vitamin D status has been associated with a variety of diseases, and biologically plausible hypotheses exist to suggest a possible causal role. However, until confirmed by randomized studies, it is wise to be cautious and recognize that association does not prove causation.
WHEN SHOULD VITAMIN D LEVELS BE ASSESSED?
There are no randomized trials advocating a population screening approach, but it seems reasonable to at least measure 25-hydroxy vitamin D in those identified as being at high risk of vitamin D deficiency, and those for whom a prompt musculoskeletal response to optimization of vitamin D status could be expected.
Such groups include those with osteoporosis, a history of falls or high risk of falls, malabsorption such as with celiac disease, radiation enteritis, bariatric surgery, individuals with liver disease, and those requiring medications known to alter vitamin D levels (certain anticonvulsants). Given the relationship of low vitamin D status with cancer, it also seems rational to measure vitamin D in those with malignancy.
APPROACHES TO VITAMIN D REPLETION/SUPPLEMENTATION
Increasing exposure to sunlight would be an effective and free approach to improving vitamin D status. However, this does not seem to be viable given widespread sun avoidance campaigns based on the association of UV exposure with skin cancer.
It could be argued that simple treatment of all individuals with vitamin D should be advocated, therefore making vitamin D measurement unnecessary. But again, there is no expert consensus regarding this recommendation, nor is there consensus regarding a recommended dose. Some recommend 800 to 1000IU daily, whereas some vitamin D experts suggest values over 2000IU per day. Vitamin D dosing may differ by age in that older adults likely require higher vitamin D intake because of the lower capability of their skin to produce vitamin D with advancing age. Similarly, clear differences exist between races, with African-Americans requiring higher intake than Caucasian-Americans.
Various “high dose” repletion approaches exist, such as 50,000 IU three times weekly or monthly. There are additional reports of recommendations using more than 600,000 IU administered over two months, plus an additional clinical report of 50,000 IU once weekly for up to three years.
Available data find daily vitamin D supplementation to be less effective than expected at increasing vitamin D status, perhaps because of failure to reliably take the supplements. A reasonable clinical “rule of thumb” is that the addition of 1000 IU of vitamin D3 daily can be expected to increase circulating vitamin D levels by approximately 10 ng/mL. Keep in mind that it can take up to three to six months for serum vitamin D
levels to plateau following initiation of supplementation.
Finally, after complaining to my mother about the nauseating taste of cod liver oil, she put this slimy, putrid medicine into a glass of orange juice, which, unfortunately, did not mask the taste. It was yet another 30 years before I could drink orange juice again. But just yesterday, I sat down to breakfast and I had a plate of geflite fish and a glass of orange juice. I did not recall the terrible taste, but I was reminded of the love and concern my Jewish mother had for my health and welfare.
July 25, 2010 | 7:18 pm
No, familial Mediterranean fever is not a fever you get when you go on a Mediterranean cruise with your family. It is a rare autosomal recessive genetic disease with recurrent fevers, rashes, and painful inflammation of the abdomen, lungs, and joints. The episodes can last up to three days at a time and, if not treated, can lead to certain complications, such as kidney failure. It primarily affects populations emanating from the Mediterranean area. The disease is very ancient – probably beginning over 2500 years ago.
I had the privilege of interviewing Dr. Terri Getzug, who is a specialist in gastroenterology and Associate Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA. Outside of Israel, Dr. Getzug is one of the few experts in Familial Mediterranean Fever (FMF), and at UCLA she directs a premiere dedicated clinic devoted to the recognition and treatment of this complex and challenging disorder.
Dr. Lavin: How do these patients present and what are their symptoms?
Dr. Getzug: Often, patients come to the doctor complaining of recurrent attacks of severe abdominal pain caused by peritonitis (an inflammation of the abdominal cavity) accompanied by fever. Sometimes, chest pain can occur due to pleuritis (an inflammation of the lung cavity). Some patients manifest arthritis (painful swelling of the joints), which occurs in 75% of North African Jews. Others develop a skin rash, and still others present with amyloidosis – a potentially deadly buildup of protein in vital organs, such as the kidney. This is the most severe complication, which, if not prevented and treated, can lead to end-stage kidney failure.
Dr. Lavin: How often do these events occur and at what age?
Dr. Getzug: As FMF is a genetic disease, it can manifest at any age after birth. The peak incidence is between 5 to 15 years of age; although it rarely can begin as late as age 30 (90% of patients are diagnosed by age 20). The frequency of attacks is variable, but specific for each patient; they can occur weekly to once annually. An episode can last 24 – 72 hours, and between attacks, patients are completely well.
Dr. Lavin: Other than the unique clinical presentation, can laboratory tests help make the diagnosis?
Dr. Getzug: Not really. Lab testing during an attack is nonspecific, but genetic testing can help make the diagnosis. This diagnosis generally is based on three factors: (1) typical clinical presentation; (2) a positive response to treatment with a medicine called colchicine; and (3) genetic testing.
Dr. Lavin: What are the long-term complications?
Dr. Getzug: The major cause of morbidity and mortality for FMF patients is secondary amyloidosis, which has declined markedly with the advent of treatment with Colchicine. Amyloid is a protein which forms in response to chronic inflammation. Amyloid deposition occurs in the kidneys, spleen, liver and gut, and to a lesser degree in other organs. The kidney is the most frequently involved organ leading to renal failure if not treated early with colchicine. Another complication is disabling arthritis, usually occurring in the hip joints and sometimes requiring hip replacement.
Dr. Lavin: Tell us about the genetic makeup of patients with FMF.
Dr. Getzug: The cloning of the FMF gene (MEFV) in 1997 made genetic testing possible. Since FMF is inherited as an autosomal recessive trait, two mutations (one from each parent) is required for clinical disease, but some patients have only one mutation and some have none detectable. Currently, with standard genetic testing, we are able to detect 13 of the most common mutations. There is a 1 in 4 chance that a child will inherit normal genes from both parents; therefore, he/she will not get the disease. There is a 2 in 4 chance that a child will inherit one mutated gene from one parent and a normal gene from the other parent; therefore, the child will be a carrier like his parents, but free of disease.
Dr. Lavin: What is the ethnic makeup of these patients?
Dr. Getzug: FMF has been described primarily in Sephardic Jews, Armenians, Turks, North Africans, Arabs and less commonly Greeks and Italians. More than 90% of Jewish FMF patients are of Sephardic or of Middle Eastern origin. In North African Jews, the carrier rate is 1 in 6, with clinical disease occurring in 1 in 256 people of that ethnic population. In Israel, the clinical disease ratio is 1 in 500. FMF affects both sexes in a similar ratio. Even though the prevalence is high, there is incomplete penetrance, so that not everyone who has the two mutated genes has the complete clinical presentation.
Dr. Lavin: What causes FMF? Is it an autoimmune disease?
Dr. Getzug: FMF is not an autoimmune disorder, like lupus for example, since it does not respond to steroids or other immunosuppressant medications, and autoantibodies have never been demonstrated. The specific cause is unknown, but it is probably an inflammatory process in which inflammation sporadically is triggered and runs unchecked, attacking specific tissues in the body.
Dr. Lavin: What is the treatment?
Dr. Getzug: Colchicine (which is used for gout) is the treatment of choice. About 80 – 90% of patients respond with complete remission, and virtually all others show some improvement in attack frequency and severity. Although the exact mechanism of action is unknown, colchicine is believed to exert its effect on a specific type of protein in white cells that may be responsible for the clinical inflammation in this disorder.
Dr. Lavin: Thank you Dr. Getzug for your expertise and your ongoing commitment to enhancing the health of the Jewish Community.
For further information contact:
Terri Getzug, M.D.
Director, Familial Mediterranean Fever Clinic
Division of Digestive Diseases
David Geffen School of Medicine at UCLA
June 6, 2010 | 11:45 pm
Persian Jewry is one of the oldest continuous Jewish communities in the world, having been isolated reproductively from other Jews, as well as other Iranians. Most now live in Israel and the United States, but before the Revolution, 150,000 Jews lived in Iran.
Because of the large Persian community in Los Angeles, Dr. David Rimoin, Director of the Cedars-Sinai Persian Jewish Genetic Screening Program, launched his center in 2009 to detect genetic diseases in this community. Recent advances allowed scientists to identify new markers for recessive genetic disorders in Persian Jews.
David Rimoin, M.D., Ph.D. is a professor at UCLA and a world-renowned genetics scholar. In 1971, he was part of the team that pioneered the first population-based screening program for Ashkenazi Jewish carriers of Tay-Sachs disease. I recently had the privilege of interviewing my esteemed UCLA colleague.
Dr. Lavin: Which disorders are most common in the Persian Jewish community?
Dr. Rimoin: There are four that we screen for at Cedars-Sinai.
(1) Pseudocholinesterase Deficiency causes sensitivity to certain forms of anesthesia, as well as other drugs. It is an inherited blood plasma enzyme abnormality, which should be made known to the anesthesiologist if you are undergoing surgery. When the anesthesiologist administers anesthesia to a patient with pseudocholinesterase deficiency, the patient experiences prolonged respiratory muscle paralysis, requiring mechanical ventilation to save the person’s life. By knowing in advance, safe drugs are selected and the paralysis will not occur. One in ten Persian Jews are carriers for anesthesia sensitivity. In one of 100 couples, both partners will be carriers; therefore 25% of their children may have the disorder.
(2) Congenital Hypoaldosteronism, (a salt-losing disorder) is a rare inherited disorder transmitted as either an autosomal recessive or autosomal trait with mixed penetrance. It is further subdivided into two types (CMO I and CMO II). Aldosterone is a hormone produced in the adrenal gland, which is important for sodium conservation. The clinical presentation of aldosterone deficiency is low sodium, high potassium, and acidosis, accompanied by short stature. Infants often are dehydrated and fail to thrive, but adults usually have no symptoms. Treatment is replacement of the absent hormone. One in 30 Persian Jews are carriers, and one in 900 Persian Jewish couples are at risk of having a child with this disorder.
(3) Autoimmune Polyendocrine Hormone Deficiency. In this condition, several hormones are deficient, but there are three main components, including: (a) a low parathyroid hormone resulting in very low calcium levels, (b) adrenal insufficiency (Addison’s Disease), which causes many symptoms including low blood pressure and weakness and (c) infection with Candida ( a yeast or fungal infection). Additional components may include Diabetes Mellitus Type I, low reproductive hormones, pernicious anemia, alopecia, and/or vitiligo. The frequency in Iranian Jews is 1 per 9,000. One in 50 Persian Jews are carriers.
(4) Hereditary Inclusion Body Myopathy is a progressive muscle disease characterized by muscle weakness developing in adults and is known as type IBM2 (autosomal recessive) in Persian Jews. It does not affect the brain or internal organs. Biopsies of the muscles in these patients reveal vacuoles with inclusions. Additional diagnostic tests include a sample of blood for creatinine kinase as well as nerve conduction studies. An MRI is helpful to determine sparing of the quadriceps and genetic testing confirms the diagnosis. Treatment is palliative – not curative. One in 20 Persian Jews are carriers, and one in 400 couples are at-risk of having a child with this condition.
Dr. Lavin: How often do these disorders occur?
Dr. Rimoin: They are as common in the Persian Jewish community as Tay-Sachs is to the Ashkenazi Jews. The carrier frequency (the possibility that someone will have one affected gene) for the four diseases ranges from 1:10 for pseudocholinesterase to 1:50 for autosomal polyglandular syndrome.
Dr. Lavin: Can we help these patients?
Dr. Rimoin: Yes. (1) For salt-losing Congenital Hypoaldosteronism, medication is readily available. (2) Autosomal Polyglandular Deficiency can also be treated with replacement hormones. (3) Patients with Pseudocholinesterase Deficiency can be easily managed during surgery, but the anesthesiologist must be made aware of this condition. (4) Unfortunately, for Hereditary Inclusion Body Myopathy, there is no cure at the present time, but preconception genetic counseling or prenatal diagnosis is available for couples in which both partners carry the mutated gene.
Dr. Lavin: Where do patients go for help?
Dr. Rimoin: The Medical Genetics Institute at Cedars-Sinai Medical Center is available to all Persian Jews. Simply contact my Center for further information.
Dr. Lavin: Besides these four diseases, are there others that testing is available for in this community?
Dr. Rimoin: Yes. We can also test for (1) Wolman disease – an untreatable illness (lipid storage disorder), which usually results in death in the first year of life and (2) Usher type II – an untreatable illness that causes deafness and poor vision.
Dr. Lavin: Should all Persian Jews be tested?
Dr. Rimoin: Yes, the program is not only for prenatal couples, but it is for every Persian Jew.
Dr. Lavin: What is the cost for testing?
Dr. Rimoin: Approximately $350 for all four tests, and if positive, we will provide genetic counseling.
Dr. Lavin: My colleagues and I applaud your compassion for the Persian Jewish Community as witnessed by the Cedars-Sinai Screening Program for these four diseases.
For further information: Call Cedar-Sinai Genetic Screening Program in Los Angeles, California 310-423-9547
May 12, 2010 | 1:54 pm
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.
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.