Brennan P & Parkes O. Case-finding in Fabry disease: experience from the North of England

SUPPLEMENTARY ONLINE MATERIAL

Male:female ratios in ‘cascade positive’ relatives

M / F / M:F
Symptomatic
first degree relatives / 4 / 4 / 1
second degree relatives / 2 / 2 / 1
> second degree relatives / 6 / 5 / 1.2
All symptomatic relatives / 12 / 11 / 0.9
Asymptomatic
first degree relatives / 5 / 18 / 0.3
second degree relatives / 3 / 9 / 0.3
> second degree relatives / 1 / 2 / 0.5
All asymptomatic relatives / 9 / 29 / 0.3
All positive cascades / 21 / 40 / 0.5

Age at diagnosis in index cases and cascade positive relatives

Group / Age range / Median age
Indexcases / 17-59 / 38
Firstdegree relatives, positive cascade / 3 - 71 / 38
Firstdegree relatives, positive cascade, symptomatic / 20 - 60 / 46
Seconddegree relatives, positive cascade / 5 - 69 / 24.5
Seconddegree relatives, positive cascade, symptomatic / 19 - 69 / 23.5
> second degree relatives, positive cascade / 13 - 63 / 42.5
> second degree relatives, positive cascade, symptomatic / 13 - 63 / 42
ALL relatives, positive cascade / 3 - 71 / 38
ALL relatives, positive cascade, symptomatic / 13 - 69 / 42

Details of patients identified with low α-galactosidase activity on dried blood spot testing (includes patients with a known diagnosis of AFD).

Patient ID / Source / Year of sample / Sex / DBS result* / Plasma
α-galactosidase / DNA analysis / Comment
1 / Metabolic medicine / 2009 / F / 3.2 / ND / ND / Known Fabry heterozygote
2 / Renal medicine / 2009 / F / 5.23 / low / IVS6-1G>C / Fabry confirmed
3 / Cardiology / 2009 / M / 1.88 / ND / c.955A>T / Fabry confirmed
4 / Metabolic medicine / 2009 / M / 3.07 / ND / ND / Known Fabry hemizygote
5 / Metabolic medicine / 2009 / M / 4.06 / ND / ND / Known Fabry hemizygote
6 / Cardiology / 2009 / M / 2.78 / ND / c.902G>A / Fabry confirmed
7 / Cardiology / 2010 / F / 2.62 / low / c.718_719del / Fabry confirmed
8 / Clinical genetics / 2010 / F / 3.95 / ND / ND / Known Fabry heterozygote
9 / Renal medicine / 2010 / M / 2.98 / normal / ND / Fabry excluded
10 / Renal medicine / 2010 / M / 1.12 / ND / ND / Known Fabry hemizygote
11 / Cardiology / 2011 / M / 4.42 / normal / ND / Fabry excluded
12 / Metabolic medicine / 2011 / F / 4.94 / low / c.718_719del** / Known Fabry heterozygote
13 / Neurology / 2011 / M / 2.98 / ND / ND / Fabry excluded
14 / Renal medicine / 2011 / M / 4.52 / normal / ND / Fabry excluded
15 / Metabolic medicine / 2011 / F / 3.03 / ND / ND / Known Fabry heterozygote
16 / Metabolic medicine / 2011 / F / 3.12 / ND / ND / Known Fabry heterozygote
17 / Renal medicine / 2011 / M / 3.69 / normal / ND / Fabry excluded
18 / Renal medicine / 2011 / M / 2.5 / normal / ND / Fabry excluded

* pmol/punch/hour (normal range = 6.3 – 47) ; ND = not done

**this patient was a known heterozygote relative of patient 7