TABLE 1: Frequency by country of homozygosity and heterozygosity for LYS329GLU (G985A) MCAD allelic variant
| Australia |
1/20,000 |
1/71 |
0 |
5 |
353 |
Anonymous spare Guthrie cards |
7 |
| Belgium |
1/24,000 |
1/77 |
0 |
13 |
998 |
Surveyed newborn blood samples |
8 |
| Bulgaria |
1/33,000 |
1/91 |
1 |
9 |
1005 |
Surveyed newborn blood samples |
8 |
| Czech Republic |
1/231,000 |
1/240 |
0 |
5 |
1201 |
Surveyed newborn blood samples |
8 |
| Denmark |
1/42,000 |
1/102 |
0 |
9 |
921 |
PKU cards |
9 |
| Finland |
1/10,000 |
1/50 |
0 |
4 |
200 |
Blood donors |
10 |
| France |
|
| - Lyon |
|
1/532 |
0 |
2 |
1064 |
Unselected newborn blood spots |
11 |
| - Aquitaine |
1/44,000 |
1/105 |
0 |
20 |
2090 |
Unselected newborn blood spots |
12 |
| - Normandy |
|
1/118 |
0 |
17 |
2000 |
Random newborn blood spots |
13 |
| - Paris |
1/19,000 |
1/140 |
0 |
6 |
414 |
Caucasian blood donors |
14 |
| Germany |
1/53,000 |
1/116 |
0 |
26 |
3015 |
Surveyed newborn blood spots |
8 |
| Hungary |
1/192,000 |
1/168 |
0 |
6 |
1008 |
Surveyed newborn blood spots |
8 |
| Italy |
1/442,000 |
1/333 |
0 |
3 |
997 |
Newborn PKU cards |
15 |
| Japan |
0 |
0 |
0 |
0 |
1000 |
Anonymous spare Guthrie cards |
7, 8 |
| Netherlands |
1/16,000 |
1/63 |
0 |
99 |
6195 |
Anonymous spare Guthrie cards |
16 |
| Poland |
1/38,000 |
1/98 |
0 |
10 |
980 |
Surveyed newborn blood spots |
8 |
| Russia |
1/27,000 |
1/83 |
0 |
5 |
413 |
Unselected newborn blood spots |
17 |
| Scotland |
1/304,000 |
1/276 |
0 |
2 |
552 |
Women AFP lab clotted blood |
18 |
| Spain |
1/82,000 |
1/141 |
1 |
5 |
1000 |
Unspecified newborn blood spots |
8 |
| Switzerland |
1/11,000 |
1/52 |
0 |
22 |
1142 |
Guthrie cards from healthy babies |
19 |
| Turkey |
1/186,000 |
1/216 |
0 |
5 |
1079 |
Surveyed newborn blood spots |
8 |
| UK |
1/17,000 |
1/64 |
0 |
158 |
10,171 |
Surplus dried blood samples |
20 |
| - Trent |
1/18,500 |
1/68 |
0 |
6 |
410 |
Neonatal population |
21 |
| - Birmingham |
1/6,400 |
1/40 |
0 |
12 |
479 |
Anonymous Guthrie cards |
22 |
| US |
|
| - NC |
1/28,000 |
1/84 |
0 |
31 |
2611 |
Caucasian PKU cards |
4 |
| - Texas |
|
1/107 |
0 |
5 |
536 |
Anonymous spare Guthrie cards |
7 |
| - Pennsylvania |
1/20,408 |
† |
4 |
5‡ |
80,371 |
Supple. newborn screening program |
5 |
*estimated from frequency of heterozygosity;
†cannot be calculated-entire population not genotyped;
‡compound heterozygotes, not including carriers
**prospective population-based study
TABLE 2: Documented allelic variants in MCADD individuals by type of mutation (1)
| LYS329GLU (G985A) |
D474 |
1102-1105 |
13-BP DUP 999(T)-1011(C) |
| GLY267ARG (G799A) |
D955-56 |
GLY90DEL & CYS91DEL |
|
| ILE375THR (T1124C) |
1189 |
|
|
| CYS244ARG (T730C) |
|
|
|
| MET149ILE (G447A) |
|
|
|
| C91Y (347G-A) |
|
|
|
| Y133X (474T-G) |
|
|
|
| T168A (577A-G) |
|
|
|
| M301T (977T-C) |
|
|
|
| S311R (1008T-A) |
|
|
|
| R324X (1045C-T) |
|
|
|
| Y327C (1055A-G) |
|
|
|
| E359X (1150G-T) |
|
|
|
| GLY170ARG (G583A) |
|
|
|
| R28C (157C-T) |
|
|
|
TABLE 3: Presenting symptoms observed in MCADD patients
| hypoglycemia |
|
96% |
91% |
| probable infection |
85% |
74% |
|
| lethargy |
84% |
100% |
26% |
| vomiting |
66% |
60% |
52% |
| coma/encephalopathy |
49% |
|
|
| respiratory arrest |
48% |
|
4% |
| hepatomegaly |
44% |
59% |
30% |
| seizures |
43% |
29% |
17% |
| apnea |
37% |
|
|
| cardiac arrest |
36% |
|
|
| sudden death |
18% |
26% |
17% |
TABLE 4: Frequency of the G985A MCAD allelic variant among SIDS patients
| 309 |
USA - Maryland |
1 |
1 |
1/309 |
31 |
| 100 |
France - Aquitaine |
0 |
1 |
1/100 |
12 |
| 1224 |
USA - California |
0 |
3 |
1/375 |
32 |
| 120 |
Denmark - Copenhagen |
0 |
1 |
1/120 |
33 |
| 233 |
W. Scotland |
0 |
3 |
1/78 |
16 |
| 262 |
USA - Maryland |
0 |
3 |
1/88 |
34 |
| 67 |
USA - New York |
0 |
3 |
1/22 |
35 |
| 119 |
USA - N. Carolina |
0 |
4 |
1/30 |
37 |
| 153 |
Germany |
0 |
0 |
|
38 |
| 708 |
Australia |
0 |
7 |
1/101 |
39 |
TABLE 5: Long-term consequences in 97 surviving MCADD patients 6 months to 9 years old (27)
| Developmental disability* |
16% |
| Speech and language delay* |
22% |
| Behavioral problems* |
15% |
| At least one of the above outcomes |
32% |
| Attention deficit disorder* |
12% |
| Proximal muscle weakness |
16% |
| Chronic seizure disorder |
14% |
| Cerebral palsy |
9% |
| Failure to thrive |
10% |
| Complete aphasia following illness |
5% |
*Out of 73 patients for whom psychodevelopmental information was available
TABLE 6: Methods for detection MCAD deficiency in newborns
| DNA/PCR |
ns† |
ns† |
ns† |
43 |
| HPLC |
100% |
75% |
87% |
44 |
| MS/MS |
100% |
100% |
ns† |
45 |
t* positive predictive value;
†ns: not specified or calculated
|
|