Table 4.
Pt # | Sex | Ethnic origin | Age at diagnosis | Current age (y) |
Biochemical phenotype |
Carboxylase activities in fibroblasts (pmol/min/mg protein)1 |
Genotype |
Clinical phenotype§ | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
DBS/ plasma |
urine |
affected gene |
Nucleotide change (at RNA level) |
Amino acid change (predicted from RNA) | |||||||||
C5OH | 3-HIVA | 3MCG | MCC | PCC | Allele 1 Allele 2 | ||||||||
37 |
f |
Asian |
32 years |
40 |
++ |
++ |
++ |
9.6 |
1268 |
MCCC2 |
c.1367C>T |
p.A456V |
asymptomatic (ltf) |
|
|
|
|
|
|
|
|
|
|
|
c.1367C>T |
p.A456V |
|
51 |
f |
Asian |
24 years |
32 |
++ |
na |
na |
0 |
475 |
MCCC2 |
c.351_353delTGG◊ - |
p.G118del - |
asymptomatic (ltf) |
73c |
f |
Faroe Islands |
29 years |
37 |
++ |
++ |
++ |
na |
na |
MCCC1 |
c.1526delG |
p.C509Sfs*14 |
asymptomatic (fr) |
|
|
|
|
|
|
|
|
|
|
|
c.1526delG |
p.C509Sfs*14 |
|
83 |
f |
Caucasian |
? |
38 |
++ |
++ |
++ |
na |
na |
MCCC1 |
c.539G>T |
p.G180V |
asymptomatic (fr) |
|
|
|
|
|
|
|
|
|
|
|
c.558delA |
p.Q186Hfs*6 |
|
85 |
f |
Caucasian |
38 years |
49 |
++ |
+ |
n |
na |
na |
MCCC2 |
c.517dupT |
p.S173Ffs*25 |
asymptomatic (ltf) |
|
|
|
|
|
|
|
|
|
|
|
c.599T>A |
p.I200N |
|
100 |
f |
Caucasian |
29 years |
34 |
++ |
++ |
++ |
na |
na |
MCCC2 |
c.505T>G |
p.Y169D |
asymptomatic (fr) |
|
|
|
|
|
|
|
|
|
|
|
c.1073-12C>G |
|
|
|
|
|
|
|
|
|
|
|
|
|
(r.1073_1216del+ r.1073insr.1073- 48_r.1073-1) |
(p.G358Vfs*6+ p.G358Afs*12) |
|
66 |
f |
Caucasian |
34 years |
41 |
+ |
+ |
++ |
10.0 |
807 |
MCCC2 |
c.436T>Ac.416_427del12ins16 |
p.Y146Np.T139_G143> RWVPGEfs*35 |
several metabolic crises with hypoglycemia during febrile illnesses, metabolic stroke, cardiomopathy, paraesthesias (ltf) |
87 |
f |
Faroe Islands |
28 years |
33 |
++ |
n |
n |
13.0 |
826 |
MCCC1 |
c.1526delGc.1526delG |
p.C509Sfs*14p.C509Sfs*14 |
chronic tiredness (fr), otherwise asymptomatic |
33 |
f |
Turkish |
36 years |
45 |
++ |
++ |
++ |
4.6 |
520 |
MCCC2 |
c.282-1G>C |
p.S95_G128del |
? |
c.282-1G>C | p.S95_G128del |
1 control values measured in 53 cell lines, expressed as median value and (range): MCC activity, 305 pmol/min/mg protein (134-671); PCC activity, 583 (208-1165); ratio of PCC/MCC activity, 1.93 (1.19 – 2.58).
§ information in brackets: fr followed regularly, ltf lost to follow-up, age of last follow-up, if known.
+ slightly elevated.
++ massively elevated; C5OH 3-hydroxyisovalerylcarnitine; DBS dried blood spots; 3-HIVA 3-hydroxyisovaleric acid; 3-MCG 3-methylcrotonylglycine; f female; fr followed regularly; ltf lost to follow-up; m male; MCC methylcrotonyl-CoA carboxylase
n normal; na not available; NBS newborn screening; PCC propionyl-CoA carboxylase; Pt # Patient number; RNA nd RNA not detectable; SMS selective metabolic screening; y years
◊ mutation heterozygous on genomic PCR, homozygous in RT-PCR; # diagnosed following the positive NBS result of their baby; ? not known.