Table 1.
Clinical, biochemical and molecular data of Brazilian MSUD patients
| ID | Gender | Age at diagnosis | Plasma isoleucine (μMol/L) at diagnosis | Plasma leucine (μMol/L) at diagnosis | Plasma valine (μMol/L) at diagnosis | Time from diagnosis to onset of dietary manegement | Outcome | Family history | Consanguinity | Clinical phenotype | Genetic subtype | Gene | Type | Mutation at nucleotide level cDNA |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1a,b | Female | 60d | 699.5 | 3252.5 | 999.5 | 60d | Severe DD + died | No | Yes | Classic | EIb | BCKDHB | Dup | c.[92_102dup11]; [92_102dup11] |
| 2c,d | Female | 30d | 45.7 | 278.9 | 35.1 | NA | Severe DD + died | Yes | Yes | Classic | EII | DBT | M | c.[346G > A];[346G > A] |
| 3c | Male | 15d | 224.4 | 2646.1 | 371.1 | 15d | Slight DD | Yes | Yes | Classic | EII | DBT | M | c.[346G > A];[346G > A] |
| 4 | Male | 26d | 149.0 | 2037.8 | 263.3 | 1d | Moderate DD | No | No | Classic | EIb | BCKDHB | D | c.[595_596delAG];[595_596delAG] |
| 5e,f,j | Male | 17d | 207.0 | 2914.0 | 304.5 | 20d | Slight DD | NA | NA | Classic | EIb | BCKDHB | D/I + D + M + M | c.[436delinsCA; 445_446delTT];[620G > T; 633G > C] |
| 6f | Female | 17d | 482.7 | 1484.0 | 942.1 | 3d | Normal neurodevelopment | No | No | Classic | EIb | BCKDHB | M + D | c.[498G > C];[595_596delAG] |
| 7 | Female | 16m | 333.0 | 1503.1 | 938.9 | NA | Slight DD | No | No | Intermediate | EII | DBT | N | c.[442G > T];[442G > T] |
| 8j | Female | 26d | 179.5 | 1488.7 | 235.1 | 15d | Severe DD | Yes | No | Classic | EIb | BCKDHB | M + D + D | c.[506A > G]; [743delC; 764_840 + 4del; 840 + 9_ + 22del] |
| 9 | Female | 60d | 1336.0 | 5002.0 | 979.0 | 15d | Severe DD | No | No | Classic | EIb | BCKDHB | N + ? | c.[853C > T];[?] |
| 10g,h | Female | NA | NA | NA | NA | NA | NA | NA | NA | NA | EIa | BCKDHA | N + SS | c.[859C > T];[109-3575_288 + 4del] |
| 11j | Male | 17d | 340.1 | 2000.0 | 409.1 | 2d | Slight DD | No | Yes | Classic | EIb | BCKDHB | D |
c.[743delC; 764_840 + 4del; 840 + 9_ + 22del]; [743delC; 764_840 + 4del; 840 + 9_ + 22del] |
| 12g | Male | 30d | 25.4 (Ile + Leu) | 3.7 | 60d | Severe DD | No | NA | Classic | Eia | BCKDHA | I + ? | c.[740_741insT];[?] | |
| 13g | Male | 30d | 31.0 | 904.1 | 406.6 | 20d | Moderate DD | Yes | No | Classic | EIb | BCKDHB | M + D | c.[502C > T];[595_596delAG] |
| 14a | Male | NA | NA | NA | NA | NA | NA | NA | NA | NA | EIb | BCKDHB | M + M | c.[605C > T];[641 T > A] |
| 15i | Male | 24 m | 895.4 | 1782.2 | 1038.2 | NA | NA | No | NA | NA | Eia | BCKDHA | M | c.[659C > T];[659C > T] |
| 16a | Female | NA | NA | NA | NA | NA | NA | NA | NA | NA | EIb | BCKDHB | M | c.[392G > T];[392G > T] |
| 17g | Female | 35d | 1700.0 | 1700.0 | NA | 10d | Severe DD | No | NA | Classic | EIb | BCKDHB | D + SS | c.[595_596delAG];[343 + 2 T > G] |
| 18 | Male | 3d | 755.0 (Ile + Leu) | 345.0 | 0d | NA | Yes | No | NA | EIb | BCKDHB | M + M | c.[392G > T];[641 T > A] | |
| 19a | Female | NA | NA | NA | NA | NA | NA | NA | NA | NA | EII | DBT | N | c.[442G > T];[442G > T] |
| 20 | Female | 14y | 220.8 | 564.6 | 493.3 | NA | Moderate or severe DD | No | No | Intermediate | EIa | BCKDHA | D + M | c.[357_358delCT];[454G > A] |
| 21 | Male | 12y | 151.2 | 580.9 | 444.3 | 2y | Moderate DD | No | No | Intermediate or thiamine responsive | EIa | BCKDHA | I + ? | c.[740_741insT];[?] |
Novel Mutations are highlighted in bold
ID patient identification, m months, d days, a years, DD developmental disability, NA data not available, M missense, Dup duplication, D deletion, I insertion, N nonsense, SS splice site
aPatient also carries the non disease-causing variation c. 116C > A in one BCKDHA allele (p.Pro39His) and the non disease-causing variation c.166G > C in one BCKDHA allele (p.Gly56Arg)
bPatient also carries the non disease-causing variation c.188_189delinsCA in one BCKDHB allele (p.Arg63Pro) and the damaging variation c.92_102dup11 in two BCKDHB alleles (p.Phe35Trpfs * 41)
cSiblings
dPatient also carries the non disease-causing novel variation c.1250A > T in one DBT allele (p.Glu417Val), probably a polymorphism in this case
ePatient also carries the non disease-causing variation c.116C > T in one BCKDHA allele (p.Pro39Leu)
fPatient also carries the non disease-causing variation c.1150A > G in one DBT allele (p.Ser384Gly)
gLiver Transplant
hPatient also carries the non disease-causing variation c. 116C > A in two BCKDHA alleles (p.Pro39His)
iPatient also carries the non disease-causing variation c.166G > C in one BCKDHA allele (p.Gly56Arg)
jPatient carries more than 2 variants, but without parental testing, it is impossible to determine which of the variants are in cis or trans configuration and what the genotype is (disease-causing and non disease-causing variations, exactly)