Table 1 Genetic, biochemical, clinical and therapeutics data concerning the cohort of 13 Portuguese PDC deficient patients
Patient | 1-JCF | 2-MJG | 3-DMN | 4-GCNa | 5-RCNa | 6-JAR | 7-ARV | 8-GMR | 9-MJP | 10-LCM | 11-AVB | 12-MBS | 13-MMS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
General information | |||||||||||||
Year of birth | 1996 | 2000 | 2005 | 2011 | 2011 | 2015 | 1983 | 2002 | 2018 | 2015 | 1988 | 2004 | 2001 |
Gender | M | M | M | M | M | M | F | M | F | F | F | F | F |
Consanguinity | N | N | NA | N | N | N | N | Y | Y | N | N | Y | N |
Age of onset (years) | 1.9 | 2 | Neonatal period | 0.6 | Neonatal period | 0.5 | 1 | 0.5 | Neonatal period | 0.5 | Neonatal period | Neonatal period | 0.4 |
Age of diagnosis (years) | 9 | 5.3 | 0.4 | 0.6 | 0.6 | 1 | 6 | 2 | Neonatal period | 3.3 | Neonatal period | 0.5 | 17 |
Actual age (years) | 23 | 19 | 14 | 8 | 8 | Deceased at 3.3 | 36 | 17 | 1 | 4 | 31 | 15 | 18 |
Genetic findings | |||||||||||||
Affected gene | PDHA1 | PDHA1 | PDHA1 | PDHA1 | PDHA1 | PDHA1 | PDHA1 | PDHX | PDHX | PDHX | PDHX | PDHX | DLD |
Affected protein componente | E1α | E1α | E1α | E1α | E1α | E1α | E1α | E3BP | E3BP | E3BP | E3BP | E3BP | E3 |
Nucleotide exchange | c.615C>G | c.757A>G | c.905G>A | c.1132C>T | c.1132C>T | c.1132C>T | c.1133G>A | c.850C>T/c.850C>T | c.850C>T/c.850C>T | c.850C>T/c.850C>T | c.850C>T/c.483delC | c.160+1G>A/c.160+1G>A | c.259C>T/c.803_804delAG |
Precursor protein Exchange | p.F205L | p.R253G | p.R302H | p.R378C | p.R378C | p.R378C | p.R378H | p.R284X/p.R284X | p.R284X/p.R284X | p.R284X/p.R284X | p.R284X/p.P161Pfs*17 | p.G26Vfs*7/p.G26Vfs*7 | p.P87S/p.Q268Rfs*3 |
Localization of mutation | Exon 7 | Exon 7 | Exon 10 | Exon 11 | Exon 11 | Exon 11 | Exon 11 | Exon 7 | Exon 7 | Exon 7 | Exon 7/Exon 4 | Intron 1 | Exon 4/Exon 9 |
Mutation type | Missense | Missense | Missense | Missense | Missense | Missense | Missense | Nonsense | Nonsense | Nonsense | Nonsense/frameshift | Splicing | Missense/frameshift |
Biochemical findings | |||||||||||||
Highest plasma lactate (mmol L−1) | 7.9 | 4.0 | 9.1 | 9.4 | 6.6 | 8.9 | 4.5 | 3.5 | 17.0 | 3.0 | 4.4 | 12.2 | 3.0 |
Highest plasma pyruvate (mmol L−1) | 0.527 | 0.300 | 0.398 | NA | 0.810 | 0.631 | 0.274 | 0.331 | 0.610 | 0.270 | 0.270 | 0.569 | NA |
Ratio L/P in same sample | 14 | 12 | 20 | NA | 8 | 14 | 16 | 16 | 14 | 9 | 16 | 16 | NA |
Enzyme activity in lymphocytes | 30 | 13 | 25b | 28 | 40 | 8.5 | 19 | 30 | 25 | 30 | 21.3/16.3b | 29 | 29 |
Clinical features | |||||||||||||
DD/MR/PMR | Moderate | Mild | Severe | Severe | Severe | Moderate | Moderate | Severe | Severe | Severe | Severe | Severe | Moderate |
Hypotonia | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | N | Y | Y |
Seizures | N | N | Y | Y | Y | Y | Y | Y | N | N | N | N | Y |
Microcephaly | Y | N | Y | N | N | N | Y | N | Y | Y | N | N | N |
Dystonia | Y | N | Y | Y | Y | Y | N | Y | N | N | Y | Y | Y |
Ataxia | Y | Y | N | Y | Y | N | N | Y | N | N | Y | Y | Y |
Peripheral neuropathy | Y | Y | NA | N | N | N | N | N | N | N | N | N | N |
Facial dysmorphisms | N | N | N | N | N | N | Y | N | N | N | N | N | N |
Spasticity | Y | N | Y | Y | Y | N | N | N | N | N | N | N | N |
Respiratory distress | N | N | Y | N | Y | Y | N | N | N | N | N | N | N |
Ocular manifestations | N | N | Cortical blindness | N | N | N | N | Strabismus | Nystagmus, loss of visual acuity | Loss of visual acuity | N | Nystagmus, strabism | Astigmatism |
Brain malformations | |||||||||||||
Basal ganglia abnormalities | Y | N | Y | Y | Y | Y | N | N | N | N | N | N | N |
Cerebral brain atrophy | Y | N | Y | N | N | N | N | Y | Y | Y | N | N | Y |
Cerebellar brain atrophy | Y | N | Y | N | N | N | N | N | N | N | N | N | N |
Therapy | |||||||||||||
Ketogenic diet | N | N | N | Y | Y | Y | N | Y | Y | Y | N | Y | N |
Thiamine | N | Y | N | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Arginine aspartate | N | Y | N | N | N | N | N | N | Y | Y | N | N | N |
Antiepiletic drugs | N | N | Y | Y | Y | Y | Y | N | N | N | N | N | Y |