A Common, Yet Often Undiagnosed Problem

I first met Mr. M, a 79-year-old man, after he fell and fractured his femur. He reported to me that for the past two years he has noted reduced sensation from his knees down and has not felt steady ambulating. This has progressed to the point where he currently spends most of his day in a wheelchair. He uses a walker or cane when transferring from his bed, chair, or car. He has continued to drive, though admitted he recognizes that it is not safe since he cannot feel the bottom of his feet, and at times is not sure whether he is applying the brakes correctly. Mr. M stated that he tries to drive on roads that are less crowded, but said that this is not always possible.

When the patient presented to the hospital with his fractured femur, the radiologist noted that he also had radiological evidence of Paget’s disease with involvement in the bone that fractured. The orthopedic surgeon chose to repair his leg in two stages, with the first being a bone biopsy to assess the integrity of his bone and to rule out Paget’s disease transformation to osteogenic sarcoma, a rare but often deadly occurrence.

He was taking thyroid medication for hypothyroidism that had been diagnosed several years ago and some medications for high blood pressure. Mr. M was anemic with borderline high mean corpuscular volume levels. He had no position or vibratory sense in his feet and was unable to feel either sharp or dull stimuli below his knees when tested. His attention span was good, though he could remember only one of three objects in five minutes, and his family reported a decline in his cognition over the past few years. Clinically, I was convinced that he had a B₁₂ deficiency and suggested that a level be obtained. His B₁₂ level returned low at 152, and a diagnosis of B₁₂ deficiency was confirmed.

While this patient is not uncommon and clearly has several serious problems, I could only wonder whether he would have been in this same situation if he had been diagnosed with a B₁₂ deficiency earlier. He reported going to a physician for his ongoing medical care and seemed to have been resigned to his disability, though he admitted that no explanation was given to him as to why he had lost his independence.

I have seen several other similar cases in the past few months, and therefore thought it would be a good idea to review B₁₂ deficiency and to raise the level of suspicion of this treatable but potentially devastating problem. While many persons who are vitamin B₁₂-deficient have a megaloblastic anemia, this is not an essential part of the problem, and other serious sequelae may be present prior to anemia being manifest, including impaired sense of smell, loss of deep-tendon reflexes, personality or memory changes, tachycardia, tingling, and numbness of the hands and feet, unsteady gait, difficulty in proprioception, neuropathic pain, and glossitis, among many others. Anemia has its own set of symptoms, including fatigue.

Dr. Thomas Addison was the first to describe what is now called pernicious anemia, though it was originally referred to as Addison’s anemia. In 1907, Dr. Richard Cabot reported a series of 1200 patients with this disorder. They had an average survival of 1-3 years, and thus the name “pernicious anemia.” In a study worthy of medical history, Dr. William Bosworth Castle was said to have performed a study whereby he ate raw hamburger meat and regurgitated it after 1 hour; he fed his stomach’s content to a group of 10 patients and compared effects to a control group that was fed untreated raw hamburger meat. The study group reportedly responded to this treatment with improvement in their anemia, leading to the conclusion that there was some “intrinsic factor” present in gastric juice that was essential.

Until 1920, pernicious anemia was considered to be a fatal disease. Dr. George Hoyt Whipple suggested using raw liver as treatment, and in 1926, it became practice to treat this disorder with daily ingestion of ½ pound of raw liver or raw liver juice from an equivalent amount of liver. In 1928, a concentrate of liver juice was marketed. For the discovery of the cure of pernicious anemia, Drs. Whipple, George Richards Minot, and William Parry Murphy were awarded the 1934 Nobel Prize in Medicine. In 1928, Edwin Cohn prepared an injectable form of liver extract, and in 1948, Drs. Karl Folkers and Alexander Todd identified cobalamin, or vitamin B₁₂, as the key factor in this extract that resulted in a cure. In the 1950s, this vitamin was purified, and methods to mass produce it were developed.

While there are several causes of vitamin B₁₂ deficiency, including bacterial overgrowth in the intestine, parasitic infestation, and rare nutritional deficiencies, most cases in the elderly are due to an autoimmune atrophic gastritis leading to reduced quantities of intrinsic factor in the gastric mucosa and a decreased ability to absorb vitamin B₁₂. This results from autoantibodies that are directed against the parietal cells leading to their loss, as well as antibodies that act against the intrinsic factor itself preventing binding to vitamin B₁₂. On occasion, parietal cell loss may result from a nonautoimmune atrophic gastritis, as may occur following chronic Helicobacter pylori infection. It should be noted that while approximately 90% of persons with pernicious anemia have antibodies against parietal cells, only 50% of individuals in the general population with these same antibodies have pernicious anemia.

Treatment is simple. For most elderly persons, vitamin B₁₂ injections can ensure an adequate circulating level of vitamin B₁₂. One should start with a daily injection of vitamin B12 1 mg for 5 days, and then change to a weekly injection of 1 mg for 1-2 months until the vitamin B₁₂ level returns to normal. Following this, a monthly injection of 1 mg is usually sufficient to maintain adequate levels. While most laboratories list the lower limit of normal serum vitamin B₁₂ as 200 pg/mL (150 pmol/L), there is some variation from lab to lab. Studies suggest, however, that associated symptoms may be present in older persons with vitamin B₁₂ levels less than 300 pg/mL, and therefore a trial of vitamin B₁₂ treatment for these individuals is worth considering. Rarely is there a need to perform the classic Schilling test in the elderly to determine the specific etiology, as a good history is usually sufficient to identify other causes, as listed above. Some advocate trying oral supplementation with vitamin B₁₂ with measurements of serum levels prior to immediately using intramuscular injections, which have become the “gold standard” for treating vitamin B₁₂ deficiencies.

As you may determine, I have been troubled by this case because I believe that early recognition and treatment of a simple vitamin deficiency may have improved this person’s functional status and quality of life. I hope that the next time you hear of similar symptoms, you too will consider a vitamin B₁₂ deficiency—a common but all-too-often forgotten problem.

Dr. Gambert is Professor of Medicine and Associate Chair for Clinical Program Development, Co-Director, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, Director, Geriatric Medicine, University of Maryland Medical Center and R Adams Cowley Shock Trauma Center, and Professor of Medicine, Division of Gerontology and Geriatric Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Send comments to Dr. Gambert at: medwards@hmpcommunications.com