Table 1.
Clinical findings in individuals with homozygous OGDH pathogenic variants, including already reported homozygous variant p.Asn320Ser4
| General and Clinical Information | Individual 1 | Individual 2 | Individual 3 | Individual 4 | Individual 5 Yap et al4 | Individual 6 Yap et al4 |
|---|---|---|---|---|---|---|
| Sex | F | M | F | F | M | F |
| Variant | c.890C>A,p.(Ser297Tyr) | c.890C>A p.(Ser297Tyr) |
c.566C>T p.(Pro189Leu) |
c.935G>A p.(Arg312Lys)/p.(Phe264_Arg312del)a |
c.959A>G p.(Asn320Ser) | c.959A>G p.(Asn320Ser) |
| Homozygous | + | + | + | + | + | + |
| Variant transcript | NM_002541 | NM_002541 | NM_002541 | NM_002541 | NM_002541.3 | NM_002541.3 |
| Age at presentation | 4 mo | 9 mo | 6 wk | 2 mo | 3 y | 8 mo |
| Age at last evaluation | 4 y | 3 y 5 months | 3 y 2 mo | Deceased at 12 mo | 6 y | 17 y |
| Global developmental delay HP:0001263 | + | + | + | + | + | + |
| Seizures HP:0001250 | + | + | – | – | – | + |
| Hypotonia HP:0001252 | + | + | + | + | + | + |
| Dystonia HP:0001332 | + | + | + | – | + | + |
| Ataxia HP:0001251 | + | + | – | – | + | – |
| Abnormal nasal bridge morphology HP:0000422 | – | + | + | + | – | – |
| Microcephaly HP:0000252 | – | + | + | + | NA | NA |
| Ventriculomegaly HP:0002119 | + | + | – | – | + | – |
| Brain atrophy HP:0012444 | + | + | – | – | – | + |
| Basal ganglia abnormality HP:0002134 | – | – | + | – | – | + |
| Corpus callosum agenesis HP:0001274 | + | – | + | – | – | – |
| Metabolic acidosis HP:0001942 | + | + | + | + | NA | NA |
| Hyperglutaminemia HP:0003217 | + | NA | + | + | NA | – |
| Hyperammonemia HP:0001987 | + | + | – | + | – | – |
| Increased serum lactate HP:0002151 | + | + | + | + | + | + |
| Elevated urinary α-ketoglutarate HP:0012401 | NA | NA | + | + | – | – |
F, female; M, male; NA, not available; +, feature present; –, feature absent.
a
The c.935G>A:p.(Arg312Lys)/p.(Phe264_Arg312del variant was found to affect splicing and cause a deletion in a mini-gene splicing assay (Figure 2F and G).