Table 1 Clinical, biochemical, cellular and molecular findings in 17 patients with MPV17 mutations
Family | Patient, sex | Consanguinity (family history) | Clinical information | Age at onset | Age at referral | Deceased/alive, age at death/current age | MPV17 mutations | mtDNA copy number in liver | mtDNA copy number in muscle | PicoGreen analysis of fibroblasts | Muscle/liver histology | Muscle/liver/fibroblasts respiratory chain activities or histochemistry |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 1, F | Y (N) | Hypotonia, progressive liver disease, coagulopathy, hypoglycaemia, developmental delay, raised blood lactate | 4.5 mo | 5 mo | Decd, 6.5 mo | c.62T>G (p.Leu21Arg) hom | ND | ND | ND | ND | ND |
2 | 2, F | N (N) | Poor feeding, FG, progressive liver disease, hypoglycaemia, raised blood lactate, delayed development, vomiting | Birth | 2 mo | Decd, 12 mo | c.67G>C (p.Ala23Pro) & c.135delA (p.Glu45Aspfs*8) | 14% | 51% | Normal | Mus: Normal; Liv: micro-and macro-vesicular change in most hepatocytes, fibrosis, inflammation | Mus: Normal; Liv: CIV↓ |
3 | 3, F | Y (Ya) | IUGR, feeding problems, hypoglycaemia, raised tyrosine within days of birth, raised blood lactate, FG, hypotonia, progressive liver failure, encephalopathy | Birth | 2 mo | Decd, 4 mo | c.107A>C (p.Gln36Pro) hom | 5% | 100% | Mosaic depletion | Liv: severe panlobular loss of hepatocytes and stromal collapse | Mus: Normal; Fib: Normal |
4 | 4, F | Y (Y, sibs P5 & P6) | Progressive neurological deterioration with peripheral neuropathy, progressive liver disease | 5 yr | 5 yr | Alive, 8.5 yr | c.121C>T (p.Arg41Trp) hom | 40% | 46% | Normal/minor changes | Mus: Normal; Liv: microvesicular steatosis and focal fibrosis | Mus: Normal; Liv: Normal |
5, F | Y (Y, sibs P4 & P6) | Progressive liver failure, FG, corneal scarring , progressive neurological deterioration | Birth | 9 mo | Decd, 4 yr 3 mo | c.121C>T (p.Arg41Trp) hom | ND | 38% | N.D. | Mus: Normal Liv: cirrhosis | ND | |
6, M | Y (Y, sibs P4 & P5) | Progressive liver failure, encephalopathy, liver transplant at 15 mo, died 15 mo later following neurological and renal deterioration. | Birth | 9 mo | Decd, 2 yr 6 mo | ND | ND | ND | ND | Liv: Giant cell hepatitis, haemorrhagic necrosis, focal fatty change | ND | |
5 | 7, M | Y (Yb, sib P8) | Poor feeding, hypoglycaemia, FG, raised blood lactate, encephalopathy, progressive liver failure | 3.5 mo | 3.5 mo | Decd, 4 mo | c.130C>T (p.Gln44*) hom | ND | ND | ND | Mus: Fatty infiltration; Liv: fatty infiltration | Mus: CI ↓, CII+III ↓, CIV ↓ |
8, F | Y (Yb, sib P7) | Tachypnoea, hypoglycaemia, raised blood lactate within days of birth, poor weight gain, progressive liver failure | Birth | Birth | Decd, 7.5 mo | c.130C>T (p.Gln44*) hom | ND | ND | Normal/minor changes | ND | ND | |
6 | 9, M | N (N) | FG, liver disease, liver transplant at 3 yr, progressive demyelinating peripheral neuropathy, hypoparathyroidism, severe growth hormone deficiency, gastrostomy | 5 mo | 5 mo | Alive, 11.5 yr | c.191C>G (p.Pro64Arg) & c.293C>T (p.Pro98Leu) | 21% | 80% | Normal | Mus: minor fatty changes; Liv: steatosis, abundant mitochondria with mild pleomorphism | Mus: CI ↓, CIV↓ Liv: CIV ↓ |
7 | 10, M | Y (N) | Neonatal jaundice, FG, hypotonia, microcephaly, progressive liver disease, raised blood lactate, retinal pigmentation | 2 mo | 2 mo | Decd, 5 mo | c.278A>C (p.Gln93Pro) hom | ND | ND | ND | Liv: distension of hepatocytes, few periportal glycogen nuclei, fibrosis, microvesicular steatosis and portal inflammation. | ND |
8 | 11, F | Y (Yc) | Poor feeding, mild hypotonia, jaundice, liver dysfunction, coagulopathy, raised blood lactate | 2 mo | 3.5 mo | Decd, <16 mo | c.278A>C (p.Gln93Pro) hom | 11% | ND | Mosaic depletion | Liv: cholestasis with scattered giant cell hepatocytes and extensive portal - portal bridging fibrosis | ND |
9 | 12, F | Y (Y, sib P13) | Poor feeding, FG, hypotonia, subtle facial dysmorphism, hypoglycaemia, cholestatic jaundice, central hypocortisolism, progressive liver disease | 2 mo | 5 mo | Decd, 8 mo | c.278A>C (p.Gln93Pro) hom | ND | 10% | ND | ND | Mus: CI ↓, CIII ↓, CIV ↓ |
13, F | Y (Y, sib P12) | Neonatal jaundice, FG, hypotonia, recurrent vomiting, progressive liver disease, raised blood lactate, retinal pigmentation | Birth | 5 mo | Alive, 6 mo | c.278A>C (p.Gln93Pro) hom | ND | ND | ND | Liv: large droplet steatosis and microsteatosis, mild iron deposition in Kupffer cells | ND | |
10 | 14, M | Y (Yd) | FG, dev delay, hypotonia, myopathy, liver disease, cholestasis; raised blood lactate | 4 mo | 5 mo | Alive, 14 mo | c.279+1G>T hom | 5% | ND | ND | Liv: micro- and macro-vesicular steatosis with canalicular cholestasis, portal fibrosis and septae formation | ND |
11 | 15, F | Y (N) | Conjugated jaundice, hypothyroidism, hypotonia, FG, developmental delay and dysmorphism | 2.5 mo | 13 mo | Decd, 3 yr | c.461+1G>C hom | ND | 25% | Mosaic depletion | Liv: Patchy hepatocellular oncocytosis and single-cell necrosis | Mus: CI ↓, CII+III ↓, CIV ↓ |
12 | 16, M | Y (N) | Poor weight gain, hypoglycaemia, FG, hypotonia, subtle dysmorphic features, progressive liver failure, encephalomyopathy | 2 mo | 3 mo | Decd, 4 mo | Del exons 3–8 hom | 14% | 17% | ND | Mus: Generalized fibre atrophy, small angular fibres; Liv: cholestasis and steatosis | ND |
17, F | Y(Y, sib P16) | Raised γGT at 6 weeks, progressive liver failure from 4 mo with rapid deterioration | Birth | Birth | Alive, 5 mo | Del exons 3-8 hom | ND | ND | Mosaic depletion | ND | ND |
