Clinical details, biochemical data and mutation spectrum in the HMBS gene in South African patients with AIP
| Patient | Sex/race | Clinical information (as far as can be established) | Urinary PBG (<1.6 µmol/mmolcreatine) | Plasma fluorescence emission peak (619 nm) | Urine total porphyrins (<26.2 nmol/mmolcreatine) | Location of mutation | Molecular defect | Predicted protein product |
|---|---|---|---|---|---|---|---|---|
| 1 | F/B* | Tetraparesis | 31.2 | Present | 111.7 | Exon 5 | c.181delG | p.Asp61Thrfs*37 |
| 2–3 | F/MA | Unknown | 28.6 | Present | 46.3 | Exon 8 | c.346C>T | p.Arg116Trp |
| F/MA | Unknown | 142.6 | Present | 888.6 | ||||
| 4 | M/B | Progressive muscular atrophy | 147.8 | Present | 259.2 | Exon 9 | c.445C>T | p.Arg149X |
| 5 | M/B | Unknown | 11.2 | Present | Unknown | Exon 10 | c.583C>T | p.Arg195Cys |
| 6 | F/B | Unknown | 31.1 | Present | 811.9 | Exon 12 | c.706G>A | p.Gly236Ser |
| 7–9 | F/B | Unknown | 58.6 | Present | 256.4 | Exon 12 | c.771_772insT | p.Leu258Leufs*33 |
| F/B | Unknown | 103.5 | Present | 590.2 | ||||
| F/MA* | Unknown | 33.7 | Present | 598.0 | ||||
| 10–13 | M/C† | Abdominal pain | 18.9 | Unknown | 71.1 | Exon 14 | c.848G>A | p.Trp283X |
| F/C† | Acute attack | 65.8 | Unknown | 201.5 | ||||
| M/C‡ | Not performing well at school | 0.4 | Normal | Not done | ||||
| F/C‡ | Asymptomatic | Not done | Not done | Not done | ||||
| 14–17 | F/MA* | Abdominal pain, weakness | 262.2 | Present | 1537.4 | No mutations found in these patients | ||
| F/B | Acute attack | 30.5 | Unknown | 136.5 | ||||
| F/MA | Chronic alcohol abuse, abdominal pain, constipation, seizures, weakness | 65.6 | Unknown | 119.1 | ||||
| F/MA | Unknown | 120.6 | Present | 154.5 | ||||
| 18–19 | M/C | Symptoms triggered by commencement of tuberculosis therapy | 37.8 | Present | 126.7 | Exon 7 | c.292A>G | p.Lys98Glu§ |
| M/C | Unknown | 12.6 | Present | 155.8 | ||||
| 20 | M/MA | Acute attack | 44.3 | Present | 376.5 | Exon 12 | c.689_690delAC | p.Asp230Aspfs*20§ |
| 21 | F/B | Abdominal pain, polyneuropathy | 43.1 | Present | 102.6 | Intron 4 | c.161-1G>A | Splicing aberration§ |
| 22 | F/B | Acute attack | 33.2 | Present | 39.5 | Intron 8 | c.422+3_6delAAGT | Splicing aberration§ |
*Patient deceased.
†Siblings.
‡Siblings and offspring of M/C†.
§Novel mutations.
AIP, acute intermittent porphyria; B: Black; C: Caucasian; F: female; HMBS, hydroxymethylbilane synthase; M: male; MA: mixed ancestry; PBG, porphobilinogen.