Appendix 2:

Vitamin-related laboratory tests in patients with definite responses to Cbl therapy




sFol, ng/mL/rFol, g/mL

MMA, nmol/L

HCys, μmol/L

BUN, g/dL/Cr, mg/dL


Case
Cbl, pg/mL
Before Rx
After Rx
Before Rx
After Rx
TSH, mIU/L
EtOH
1   137; 235   18.8/611   ”< 400”   ND   ND   ND   ND   1.6   No  
2   163; 156   17.9/ND   1829   180   40.4   13.9   27/1.0   1.5   Yes  
3*  281; 343   6.6/229   419; 363   183   40.4; 60.7   75.8  11/1.2   2.75   Yes  
4   159   ND/288   ”< 400”   ND   4.5   ND   5/0.4   1.7   No  
5   201; 201   ND/ND   ND   172   ND   ND   19/0.6   0.7   No  
6  216; 275   5.6/ND   600   ND  39.9   ND  42/2.1   1.2   No  
7   356; 234   > 20/280   444; 389   138   5.9   ND   12/0.7   1.3   No  
8   225; 218   ND/ND   549; 497   237   3.0   ND   14/0.7   ND   No  
9   281; 343   > 20/ND   546; 426   209   18.5; 15.5   11.4   25/1.3   2.8   No  
10   416; 806   13.4/ND   321; 274   199   9.8; 11.0   7.9   32/1.1   1.55   No  
11   942   16.3/ND   314   385   16.8   17.8§  26/2.3   ND   No  
12   364; 545   > 20/ND   202; 244   113   16.1; 11.8   9.0   11/1.1   0.38   No  
13   409   ND/ND   145   ND   8.9   ND   19/1.0   ND   No  
14   916   > 20/ND   326; 286   223   16.7; 17.5   14.8   20/1.3   ND   No  
15   567; 706   17.1/ND   323; 313   199   12.2; 13.7   11.5   18/1.2   1.16   No  
16   279; 263   > 20/ND   257   137   13.2   10.4   16/1.0   5.38   No  
17   287; 329   12.7/ND   362; 288   256   17.7; 14.4   8.9   26/0.9   4.6   No  
18   423; 420   12.3/ND   397; 328   253   10.7; 8.0   8.8   22/1.4   1.85   No  
19   297; 298   14.2/ND   478; 377   255   11.9; 11.4   10.7   17/0.8   4.1   No  
20   762   ND/ND   140   ND   9.4   ND   13/1.0   4.08   No  
21   517; 565   13.7/ND   164; 157   ND   12.0; 11.4   ND   12/1.2   2.45   No  
22   344; 337   12.2/ND   309; 261   171   17.9; 17.2   17.1   17/1.1   2.64   Yes  
23   478; 458   > 20/ND   258; 305   166   9.4   ND   16/1.1   1.44   No  
24   522   ND/ND   137   ND   8.7   ND   10/0.9   1.31   No  
25   174; 253   ND/ND   ND   ND   ND   ND   7/0.5   0.80   No  
26   344   14.7/203   375   121   10.4   ND   18/0.7   0.92   No  
27   155   ND/346   1928   189   29.3   7.2   11/0.8   ND   No  
28   587   7.9/ND   255; 298   179   18.1; 18.4   13.8   23/1.4   ND   No  
29   469   > 20/ND   270; 329   202   8.9   7.0   17/0.9   0.72   No  
30   724; 537   > 20/ND   265; 288   222   14.6; 11.1   6.2   15/0.8   3.36   No  
31   540; 605   ND/ND   312; 349   165   4.8; 7.2   ND   10/0.8   2.28   No  
32   286; 357   18.2/ND   590; 487   119   13.6; 18.9   14.0§  58/2.4   1.87   No  
33   161   14.3/ND   1006   133   9.8   5.5   9/0.9   1.29   No  
34   270; 279   ND/ND   425; 639   132   11.3; 13.1   7.8   10/1.0   2.2   No  
35   370   > 20/ND   296   143   9.4   6.5   21/1.1   0.60   No  
36   356   11.0/ND   222   ND   10.5   ND   16/1.3   1.06   No  
37
 
1623; 675
 
> 20/935
 
341; 520
 
300
 
11.4; 17.2
 
9.3
 
23/1.4
 
2.08
 
No
 



sFol, ng/mL/rFol, g/mL

MMA, nmol/L

HCys, μmol/L

BUN, g/dL/Cr, mg/dL


Case
Cbl, pg/mL
Before Rx
After Rx
Before Rx
After Rx
TSH, mIU/L
EtOH
1   137; 235   18.8/611   ”< 400”   ND   ND   ND   ND   1.6   No  
2   163; 156   17.9/ND   1829   180   40.4   13.9   27/1.0   1.5   Yes  
3*  281; 343   6.6/229   419; 363   183   40.4; 60.7   75.8  11/1.2   2.75   Yes  
4   159   ND/288   ”< 400”   ND   4.5   ND   5/0.4   1.7   No  
5   201; 201   ND/ND   ND   172   ND   ND   19/0.6   0.7   No  
6  216; 275   5.6/ND   600   ND  39.9   ND  42/2.1   1.2   No  
7   356; 234   > 20/280   444; 389   138   5.9   ND   12/0.7   1.3   No  
8   225; 218   ND/ND   549; 497   237   3.0   ND   14/0.7   ND   No  
9   281; 343   > 20/ND   546; 426   209   18.5; 15.5   11.4   25/1.3   2.8   No  
10   416; 806   13.4/ND   321; 274   199   9.8; 11.0   7.9   32/1.1   1.55   No  
11   942   16.3/ND   314   385   16.8   17.8§  26/2.3   ND   No  
12   364; 545   > 20/ND   202; 244   113   16.1; 11.8   9.0   11/1.1   0.38   No  
13   409   ND/ND   145   ND   8.9   ND   19/1.0   ND   No  
14   916   > 20/ND   326; 286   223   16.7; 17.5   14.8   20/1.3   ND   No  
15   567; 706   17.1/ND   323; 313   199   12.2; 13.7   11.5   18/1.2   1.16   No  
16   279; 263   > 20/ND   257   137   13.2   10.4   16/1.0   5.38   No  
17   287; 329   12.7/ND   362; 288   256   17.7; 14.4   8.9   26/0.9   4.6   No  
18   423; 420   12.3/ND   397; 328   253   10.7; 8.0   8.8   22/1.4   1.85   No  
19   297; 298   14.2/ND   478; 377   255   11.9; 11.4   10.7   17/0.8   4.1   No  
20   762   ND/ND   140   ND   9.4   ND   13/1.0   4.08   No  
21   517; 565   13.7/ND   164; 157   ND   12.0; 11.4   ND   12/1.2   2.45   No  
22   344; 337   12.2/ND   309; 261   171   17.9; 17.2   17.1   17/1.1   2.64   Yes  
23   478; 458   > 20/ND   258; 305   166   9.4   ND   16/1.1   1.44   No  
24   522   ND/ND   137   ND   8.7   ND   10/0.9   1.31   No  
25   174; 253   ND/ND   ND   ND   ND   ND   7/0.5   0.80   No  
26   344   14.7/203   375   121   10.4   ND   18/0.7   0.92   No  
27   155   ND/346   1928   189   29.3   7.2   11/0.8   ND   No  
28   587   7.9/ND   255; 298   179   18.1; 18.4   13.8   23/1.4   ND   No  
29   469   > 20/ND   270; 329   202   8.9   7.0   17/0.9   0.72   No  
30   724; 537   > 20/ND   265; 288   222   14.6; 11.1   6.2   15/0.8   3.36   No  
31   540; 605   ND/ND   312; 349   165   4.8; 7.2   ND   10/0.8   2.28   No  
32   286; 357   18.2/ND   590; 487   119   13.6; 18.9   14.0§  58/2.4   1.87   No  
33   161   14.3/ND   1006   133   9.8   5.5   9/0.9   1.29   No  
34   270; 279   ND/ND   425; 639   132   11.3; 13.1   7.8   10/1.0   2.2   No  
35   370   > 20/ND   296   143   9.4   6.5   21/1.1   0.60   No  
36   356   11.0/ND   222   ND   10.5   ND   16/1.3   1.06   No  
37
 
1623; 675
 
> 20/935
 
341; 520
 
300
 
11.4; 17.2
 
9.3
 
23/1.4
 
2.08
 
No
 

Normal values not given in the body of text were as follows: sFol, more than 5.4 ng/mL; rFol, 145 ng/mL or more; BUN, 7 to 30 mg/dL; Cr, 0.5 to 1.3 mg/dL; TSH, 0.35 to 5.50 mIU/L.

Cbl indicates cobalamin; sFol, serum folate; rFol; red cell folate; MMA, methylmalonic acid; HCys, homocysteine; BUN, blood urea nitrogen; Cr, serum creatinine; TSH, thyroid stimulating hormone; EtOH; ethanol abuse; before Rx, prior to cobalamin therapy; after Rx, after cobalamin therapy; ND, not done.

*

Patient 3 had both hematologic and neurologic responses to Cbl therapy

HCys level returned to normal when patient 3 abstained from EtOH.

Patient 6 later relapsed off Cbl therapy with an MMA value of 1110 nmol/L and an HCys value of 32.2 μmol/L. Reinstitution of Cbl therapy led to a fall of MMA to 332 nmol/L and HCys to 18.7 μmol/L despite a persistent serum creatinine level of 2.2 mg/dL.

§

Persistent high HCys level in these patients (patients 11 and 32) may relate to chronic renal failure (creatinine, 2.3 and 2.4, respectively).

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