Background and Purpose
Unlike pernicious anemia, neurological complications of cobalamin
deficiency is increasing in the aged population. Nutritional and digestive
problems, instead of autoimmune disorder, are more common causes of cobalamin
deficiency in the elderly.
Diagnosis of cobalamin deficiency depends on clinical symptoms and
signs in conjunction with the laboratory evidence of either the metabolic consequences of this
deficient state or a serum cobalamin level below normal range. The availability
of laboratory tests varies in different parts of the world. In some countries,
MCV is the only test available and therapy begins without further confirmation
tests. In Taiwan, serum level of cobalamin has been used as one of the required
screen test for treatable dementia by the National Health Insurance (NHI). This
practice guideline is not without question.
In recent years, it becomes clear that a normal cobalamin (cbl) level is
not sufficient to exclude cobalamin deficiency as the cause of polyneuropathy,
depression or dementia. In our previous study on cobalamin levels in long term
nursing home residents with history of strokes, MCV above 100
was seen in only 4 out of 11 subjects with low cobalamin, low folic acid levels or both in serum. In
countries where determination of methyl malonic acid (MMA) level is
available, the diagnosis of cbl deficiency as the cause of polyneuropathy,
depression, mild cognitive impairment (MCI), or dementia can easily be
established. In other countries where mma level can not be obtained, MCI, early
cases of dementia or polyneuropathy from
cbl deficiency may be missed if the level of cbl is in low normal range.In
order to detect these difficult cases, we add the homocysteine (Hcy) level and
the clinical response to cbl supplement to the diagnostic criteria of probable cbl
deficiency in clinical practice.
Method
A prospective observational study on all patients referred to the
neurology service for evaluation of sensory complaints, MCI and dementia. All
patients with clinical manifestations compatible with cbl deficiency were
carefully evaluated, and pertinent laboratory data obtained (Group I). Patients with clinical and
laboratory evidence of cbl deficiency were grouped as clinical definite.
Patients with cbl level in low normal range (low: below 200pg/ml,low normal :
200-350pg/ml) , increased Hcy level (over 12 micro mol /L) and response to cbl
replacement were grouped as clinical probable (GroupⅡ). The clinical and laboratory features of these patients were
compared.
Results
Ten patients (Group I) were identified as clinical
definite cases of cbl deficiency. Four patients (GroupⅡ) were found to have cbl level in low normal range and normal Folic acid level but with elevated Hcy level and improvement of dementia and
polyneuropathy after cbl supplement. (Table 1)
In Group I, there were three patients
with cobalamin deficiency from autoimmune disorders (Gr.Ia), all were males
above age 65 and averaged age was 69 at the time of diagnosis. One had subacute
combined degeneration of cord, polyneuropathy and depressed mood without
dementia or MCI. The other two had polyneuropathy and MCI (MMSE 28/30). Seven patients had
cobalamin deficiency from dietary nutritional causes and digestive problems or
post-subtotal gastrectomy state were grouped as Gr.Ib.
The average age of this group is 80 and male to female ratio is 3 to 4. Three
presented with polyneuropathy, two presented with dementia and the rest two, with combined dementia and
polyneuropathy.
GroupⅡ has 4 male patients , age ranged from 55 to 89, averaged at 75.
One presented with sensory complaint only, two with MCI or dementia plus
polyneuropathy. The last one was with persistent dizzy feeling responded to
cobalamin supplement. Two younger patients were vegetarian without dietary
supplement of vitamin. The other two patients were elderly with mixed nutritional and digestive
problems.
Conclusion
1.
Under-diagnosis
and delayed-diagnosis of cobalamin deficiency is a problem of geriatric health
care in Taiwan.
2.
In order to
treat or prevent dementia, early diagnosis and treatment of cobalamin
deficiency is important. Along this line of thinking, the “normal range” of
serum cobalamin level can be miss-leading and addition of a warning to
physician may be necessary.
3.
Although
most patients of cbl deficiency can easily be diagnosed by careful clinical
evaluation and cbl level. there are patients with normal cbl level and clinical
evidence of cbl deficiency in neurological service. In countries where MMA level
is not available, Hcy level and empirical treatment with cbl may be a practical
way to manage these patients.
4.
Autoimmune
disease, thyroid-gastric type of pernicious anemia, sub-acute combined
degeneration of spinal cord exists in Taiwanese population. Three female cases
had been reported in Taiwanese medical literature before this study.
Discussion
In Taiwan, as in many other country with growing elderly
population, cobalamin deficiency is becoming a problem of public health rather
than a problem of individual patient. Current diagnostic criteria applied in
the neurology community as well as adopted by the NHI has apparent
shortcomings, and from the stand point of preventive medicine, is
inappropriate. It is quite obvious that, in patients with low normal serum
cobalamin level, and in some other patients with abnormal cobalamin binding
protein or increased proportion of biologically inactive form of cobalamin, a
laboratory test measuring the levels of a product of the metabolic pathways which require cobalamin as
coenzyme is necessary. MMA is the best choice but the availability is limited
due to the cost and technical problems. Alternatively, measuring Hcy level and
therapeutic trial with oral methylcobalamin may be a reasonable choice in these
countries.
Legends: (figures1,2), Male:25;Female:32, Total:57, mean
age:78.8. 7% had low Vitamin B12, 17.5% had low folic acid, total 11
subjects, only 4 had MCV >100. In 7 subjects with MCV>100,4 had either
Folic acid or Vitamin B12 level below normal. (Nutritional status,
Folic acid and Vitamin B12 level in Nursing Home Residents,
TMC89-Y05-A115)
References
1.
Pernicious
Anemia in Two Cases of Subclinical Hypothyroidism
Jin-Yng Lu et al 內科學誌 2000;11:126-131
2.
Development
of Rheumatoid Arthritis in a Patient with Pernicious Anemia: Case Report
Pao-Lin Wang, MD et al Chang Gung Med J
Vol.24 No.2 February 2001 125-128
這幾年
藥物引起的
笑氣濫用
浮出檯面
多注意麻醉
笑氣
其他慢性用藥。糖尿病用藥。
