Table 1 Clinical characteristics of late-onset type and control GA1 patients (listed according to age at first MRI)
Age at dia-gnosis. | Gender (nation of origin) | Mode of diagnosis | Clinical symptoms until and/or at diagnosis | Clinical status at last follow-up visit (age in years) | Macro-cephaly | Biochem. phenotype: low/high excretor, GA and 3-OH-GA [mmol/mol Crea] at diagnosis unless otherwise stated | Mutation analysis of GCDH gene (chr. 19p13.2) | Resid. enzyme activity | |
|---|---|---|---|---|---|---|---|---|---|
Pat. # | |||||||||
p1 a | 8.5 years | F (German) | targeted metab. scr. | nausea, vertigo | asympt. (17) | no | High GA 973 3-OH-GA 47 | p.Arg128Gln/p.Glu414Lys | n.d. |
p2 b | 15 years | M (German) | targeted metab. scr. | vertigo, headache, ↓motor balance, ↓fine mot. skills | Headaches (15) | yes (since infancy) | High strong elevation (no quantit.) | p.Arg88Cys,/p.Arg88Cys | <1% |
p3 | 22 years | F (Syrian) | targeted metab. scr. | none; path. NBS of 1st child (maternal GA1) | Headaches (22) | no | High GA 1742 3-OH-GA 124 | p.Pro128Gln/p.Pro128Gln | n.d. |
p4 | 29 years | F (German) | targeted metab. scr. | none; path. NBS of 2nd child (maternal GA1) | headaches, coordination deficits, cognitive disability (40) | no | High GA 1527 3-OH-GA 94 | p.Arg128Gln/Arg402Trp | n.d. |
p5 | 18 years | F (German) | targeted metab. scr. | headache | asympt. (31) | no | High GA 1590, 3-OH-GA 133 (at last visit; n.d. at diagnosis) | p.Tyr74Thrfsa68/p.Arg132Gly | n.d. |
p6 | 25 years | F (Turkish) | high risk scr. | none; mother of index patient | headaches, intermitt. vertigo (38) | yes (noted at diagn.) | High strong elevation (no quantit.) | n.d. (Glu365Lys/p.Glu365Lys detected in four other family members) | <1% |
p7 | 71 year | M (German) | targeted metab. scr. | repetitive cerebral ischemia, intention tremor ≥62 years confusion,↓memory ≥ 65 years epilepsy ≥72 years | progressive dementia, tremor, epilepsy, dysdiadochokinesis, incontinence (73) | yes (noted at diagn.) | High GA 2149 (FU: 452) 3-OH-GA 99 on FU (n.d. at diagnosis) | p.Arg402Trp/p.Ala421Val | n.d. |
p8 b | 66 years | M (German) | targeted metab. scr. | headache ≥35 years tremor ≥50 year seizures ≥54 years dementia, ↓speech ≥63 years | dementia, tremor, epilepsy, ↓speech, intermitt. orofac. dyskinesia, dysmetria, ↓fine motor skills (66): | yes (since infancy) | High GA 1595, 3-OH-GA 109 | p.Arg383Cys/p.Arg383Cys | n.d. |
Contr. # | |||||||||
c1 c | 8 d | F (German/ Italian) | NBS | - | asympt. (12) | no | High GA 3695 3-OH-GA 77 | p.Pro248Leu/p.Pro248Leu | 1.5% |
c2 c | 17 d | M (German) | NBS | - | asympt. (13) | no | High GA 4509 3-OH-GA 128 | p.Arg313Trp (maternal origin)/no paternal mutation found | 1% |
c3 | 10 week | F (Swiss) | NBS/targeted metab. scr. | macrocephaly | asympt. (9) | no (init. yes) | Low GA 33; 3-OH-GA 17.5 | p.Arg227Pro/p.Arg88Cys | n.d. |
c4 | 10 d | M (German/ Indonesian) | NBS (younger sib. of c7) | - | asympt. (16) | no | Low GA 7; 3-OH-GA 25 | p.Phe236Leu/p.Ser259Pro | 3% |
c5 | 13 m | F (German/ Mauretania) | high risk scr. (affected twin sister) | - | asympt. (11) | no | Low GA 6 (on FU at 2.5 years) 3-OH-GA 24 (on FU at 2.5 y)rs | p.Ala421.Val/p.Met405.Val | n.d. |
c6 c | pre-natal | M (German) | high risk scr. (younger sib. of c6) | - | asympt. (24) | yes | High GA >2.000 3-OH-GA 50 | p.Gly185Ala/p.Cys176 Arg | n.d. |
c7 | 3 m | M (German) | targeted metab. scr. | macrocephaly | asympt. (26) | yes | High GA 2670, 3-OH-GA elevated (no quant.) | p.Gly185Ala,/p.Cys176Arg | n.d. |
c8 | 36 m | M (German/Indonesian) | targeted metab. scr. | global dev. delay (≥24 m) | vertigo (21) | no | Low GA normal (not detectable), 3-OH-GA 25 | p.Phe236Leu, p.Ser259Pro | 3% |