Table 2.
Clinical and molecular information of the proband and relatives with mutation in α-galactosidase A (GLA). Normal values of α-galactosidase A activity assayed in whole blood are >2.6 μmol/l/h. Normal values of lyso-Gb3 are <1.8 ng/mL. The cause of end-stage renal disease refers only to kidney transplant recipients (proband).
| Patient | Kinship | Gender | Age at Diagnosis | Cause of ESRD | Enzimatic Activity | Lyso Gb3 | Mutation in cDNA | Protein Change | Classification of GLA Mutation | Clinical Information | Treatment | Serum Creatinine (Mg/dl) | Follow Up |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Proband | F | 60 | Unknown | 1.6 | 1.2 | heterozygous mutation c.337T > C(p.Phe113Leu) | p.F113L | Pathogenic | ESRD. No other Fabry-related symptoms | None | End-stage renal disease | 3 years. No new events |
| Sister | F | 50 | 1.5 | 2.6 | heterozygous mutation c337T > C (p.Phe113Leu) | p.F113L | Pathogenic | Proteinuria (>2 g/die), Cerebral disorders, mild renal impairmaent | algasidase α | 1.1 | 3 years. Stable renal function. One episode of transient ischemic attack | ||
| Sister | F | 61 | 3.25 | 1.6 | heterozygous mutation c337T > C (p.Phe113Leu) | p.F113L | Pathogenic | Asymptomatic | 0.8 | 3 years. No new events | |||
| Sister | F | 63 | 3.65 | 1.5 | heterozygous mutation c337T > C (p.Phe113Leu) | p.F113L | Pathogenic | Asymptomatic | 0.9 | 3 years. No new events | |||
| Son | M | 40 | 0.3 | 3.1 | heterozygous mutation c.337T > C | p.F113L | Pathogenic | Proteinuria (>600 mg/die) | Migalastat | 0.8 | 3 years. Stable renal function | ||
| Daughter | F | 33 | 3.4 | 1.5 | hemizygous mutation c337T > C (p.Phe113Leu) | p.F113L | Pathogenic | Asymptomatic | 0.7 | 3 years. No new events | |||
| Daughter | F | 36 | 3.5 | 1.7 | heterozygous mutation c337T > C (p.Phe113Leu) | p.F113L | Pathogenic | Asymptomatic | 0.6 | 3 years. No new events | |||
| Daughter | F | 36 | 2.8 | 1.7 | hemizygous mutation c.337T > C (p. Phe113Leu) | p.F113L | Pathogenic | Asymptomatic | 0.7 | 3 years. No new events | |||
| Nephew | F | 26 | 2.9 | 1.1 | heterozygous mutation c.337T > C (p.Phe113 Leu) | p.F113L | Pathogenic | Asymptomatic | 0.6 | 3 years. No new events | |||
| 2 | Proband | M | 52 | Unknown | <0.1 | 4.3 | hemizygous mutation c493G > C (p.Asp165His) | p.D165H | Pathogenic | End-stage renal disease, hypertrophic cardiomyopathy, abdominal pain, angiokeratomas | algasidase α | 1.7 | 8 years. Worsening of renal function. Heart dysfunction. Angiokeratomas |
| Daughter | F | 23 | 0.9 | 2.2 | heterozygous mutation c493G > C (p.Asp165His) | p.D165H | Pathogenic | Proteinuria (>600 mg/die) | algasidase α, then migalastat | 0.9 | 8 years. Stabilization of renal function | ||
| 3 | Proband | F | 36 | Unknown | NA | 1.5 | heterozygous variant c.937G > T (p.Asp313Tyr) | p.D313Y | Uncertain | ESRD. No other Fabry-related symptoms | 2.4 | 8 years. Worsening of renal function | |
| Father (living donor) | M | 58 | 2.7 | hemizygous variant c.937G > T (p.Asp313Tyr) | p.D313Y | Uncertain | Asymptomatic | 0.8 | 8 years. No new events | ||||
| 4 | Proband | F | 44 | Unknown | NA | 1.4 | heterozygous mutation c.376A > G (p.Ser126Gly) | p.S126G | Pathogenic | End-stage renal disease. No other Fabry-related symptoms | 0.9 | 3 years. No new events | |
| 5 | Proband | F | 58 | Unknown | 8 | 3.2 | heterozygous mutation c.658 C > T (p.R220X) | p.R220X | Pathogenic | End-stage renal disease, hypertrophic cardiomyopathy | algasidase β | 1 | 8 years. Stabilization of renal fucntion and cardiomyopathy |
| Brother | M | 53 | 1.4 | 3.5 | hemizygous mutation c.658 C > T (p.R220X) | p.R220X | Pathogenic | Cerebral disorders | algasidase α | 0.8 | 8 years. No new events | ||
| Sister | F | 62 | 6 | 3.8 | heterozygous mutation c.658 C > T (p.R220X) | p.R220X | Pathogenic | Cerebral disorders | algasidase α | 0.8 | 8 years. No new events | ||
| 6 | Proband | F | 59 | Hemolytic-uremic syndrome | 4.9 | 1.3 | heterozygous mutation c. 937 g > T (p. D313Y) | p.D313Y | Benign | End-stage renal disease. No other Fabry-related symptoms | 0.9 | 5 years. No new events | |
| Mother | F | 86 | 5.4 | 1.2 | heterozygous mutation c. 937 g > T (p. D313Y) | p.D313Y | Benign | Asymptomatic | 0.7 | 5 years. No new events | |||
| Daughter | F | 22 | 4.21 | 1.3 | heterozygous mutation c. 937 g > T (p. D313Y) | p.D313Y | Benign | Asymptomatic | 0.7 | 5 years. No new events | |||
| Daughter | F | 25 | 5.8 | 1.4 | heterozygous mutation c. 937 g > T (p. D313Y) | p.D313Y | Benign | Asymptomatic | 0.7 | 5 years. No new events | |||
| 7 | Proband | F | 60 | Interstitial nephritis | NA | 1.1 | heterozygous mutation c.376AA > G (p.Ser126Gly) | p.S126G | Pathogenic | End-stage renal disease No other Fabry-related symptoms | 0.9 | 2 years. No new events | |
| Sister | F | 56 | NA | 1.3 | heterozygous mutation c.376AA > G (p.Ser126Gly) | p.S126G | Pathogenic | Asymptomatic | 0.6 | 2 years. No new events |
ESRD: end-stage renal disease.