Supplemental data

Questionnaire

1. At what age was the diagnosis made?
2. What were the clinical symptoms at the time of diagnosis?
3. How was the diagnosis made?
4. What is the exact mutation for this patient?
5. At what age was the treatment started?
6. Mode of treatment (IM vs PO) -until what age for each?
7. What form of B12 was used (hydroxycobalamin, cyanocobalamin)?
8. How often was B12 given? Did you adjust dose based on specific marker(s) and if yes, which marker(s) did you use?
9. If there were any formal developmental assessments what was the outcome? (if none was done, please indicate “N/A”)
10. Outcome:
- How old was the patient at the last evaluation?
- Was the patient at school at the last evaluation? Working?
- Highest Level of education achieved?
- Living independent?
- Did the patient have a family/children?
- Any Medical complications?

Table 6: All TC II cases and mutations identified based on our cohort and literature review

Patient ID # / Mutation
HGMD # Accessed 2013/02/14 / Impact on protein level / Reference
#1-3 / c.427+2T>G
c.427+2T>G
HGMD # CS034069 / in-frame
deletion of 81 nucleotides due to an intron 3 donor splice mutation
activating a cryptic splice site in exon 3 / Namour et al 2003
Bibi et al 1999
#4-5 / c.330dupC
c.330dupC
HGMD # CI096317 / premature stop codon / Ratschmann et al 2009
#6-8 / c.1195C>T
c.1195C>T
HGMD # CM087884 / p.R399X / Prasad et al 2008
#9 / c.348_349delTG
c.348_349delTG
Novel this paper / Hitzig et al 1974
Arlet et al 2002
#10 / Biochemical diagnosis, molecular analysis not performed / Arrabal et al 1998
#11 / Biochemical diagnosis, molecular analysis not performed / Arrabal et al 1998
#12-13 / c.1106+1G>A
c.1106+1G>A
HGMD # CS106900 / p.E371fsX372 Exon 7 skipping / Nissen et al 2010
#14 / c.580+1G>C
c.580+1G>C
HGMD # CS106930 / Exon 4 skipping / Schiff et al 2010
#15 / c.497_498delTC
c.1139dupA / p.L166PfsX7 / Schiff et al 2010
#16 / c.497_498delTC
c.497_498delTC
HGMD # CD106933 / p.L166PfsX7 / Schiff et al 2010
#17 / c.501_503delCCA
c.1115_1116delCA / Schiff et al 2010
Souied et al 2001
#18-19 / c.927-930delTCTG
22q12.2 del involving exons 1 to 7 of TC gene / p.C309WfsX50
22q12.2 deletion leading to loss of exon 1 to 7, / Li et al 1994
#20 / c.423delC
c.937C>T
Novel this paper, both / 141fsX206 p.R313X / Namour et al 2003
Bibi et al 1999
#21 / c.940+283_286delTGGA; c.940+303_1106
+764del2152insCTGG
c.940+283_286delTGGA; c.940+303_1106
+764del2152insCTGG
Novel this paper / Exon 7 is
deleted; fsX383 / New patient
#22-23 / c.497_498delTC
c.497_498delTC
HGMD # CD106933 / p.L166PfsX7 / New patients
#24-25 / c.1013_1014 delinsTAA
c.1013_1014 delinsTAA
Novel this paper / p.S338IfsX27 / New patients
#26-29 / c.1106+1516_1222 +1231del5304
c.1106+1516_1222 +1231del5304
Novel this paper / New patients
#30 / c.744delG
c.744delG / New patient
#31 / c.1236_1237del
c.1236_1237del / stop codon in exon 9 / Schiff et al 2010
#32 / c.580+624A>T / p.fs209X / Haberle et al 2009
#33 / c.940+303_c.1106+746del2152insCTGG / p.fs326X / Haberle et al 2009
#34 / No mutation reported / Gururangan et al 2008
#35 / Biochemical diagnosis, molecular analysis not performed / Grech et al 2001
#36 / r.31C>G / Qian et al 2002
#37 / r.62G>A / Qian et al 2002
#38 / r.79G>A / Qian et al 2002
#39 / r.145C>T / Qian et al 2002
#40 / r.254T>A / Qian et al 2002
#41 / r.257G>A / Qian et al 2002
#42 / r.472G>T / Qian et al 2002
#43 / Biochemical diagnosis, molecular analysis not performed / Thomas et al 1997
#44 / No mutation reported (paper prior to TCN2 gene discovery) / Kaikov et al 1991
#45 / No mutation reported (paper prior to TCN2 gene discovery) / Mayes et al 1987
#46 / No mutation reported (paper prior to TCN2 gene discovery) / Zeitlin et al 1985
#47 / No mutation reported (paper prior to TCN2 gene discovery) / Carmel et al 1984
#48 / No mutation reported (paper prior to TCN2 gene discovery) / Rana et al. 1983
#49 / No mutation reported (paper prior to TCN2 gene discovery) / Burman et al 1979