我對台灣B12缺乏的臨床觀察 澳洲發表

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 

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