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Table 1 Genetic, biochemical, clinical and therapeutics data concerning the cohort of 13 Portuguese PDC deficient patients

From: Pyruvate dehydrogenase complex deficiency: updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese 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
  1. DD/ MR/PMR—development delay, mental retardation, psychomotor retardation
  2. Normal levels of plasma lactate—< 2.2 mmol/L
  3. Normal levels of plasma pyruvate—< 0.180 mmol/L
  4. Normal L/P ratio—< 20
  5. Y—yes; N—no; NA—not available
  6. aTwins
  7. bEnzyme activity in fibroblasts
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