Table 2:
Clinical symptoms and signs, morphological and biochemical findings, and serum FGF-21 concentrations in children with mitochondrial disorders, child disease controls, and children with LCHADs, listed by participants’ numbers
| Sex | Age at onset (years) | Age at serum sampling (years) | Age at death (years) | Main clinical features | Lactate (mmol/L) | Pyruvate (μmol/L) | Lactate: pyruvate | CK (U/L) | Liver dys-function* | Muscle histology | Biochemical analysis | DNA diagnosis | FGF-21 (Pg/mL) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Muscle-manifesting mitochondrial disorders | ||||||||||||||
| 64 | M | 0.3 | l.3† | 1.4 | Alpers-Huttenlocher syndrome | 7.2‡ | 156‡ | 46‡ | 163 | Yes | RRF, COX-neg | CI, CIV | POLG heterozygous | 4358‡ |
| 65 | M | 0.2 | 0.3† | Alive | Reversible COX deficiency | 7.0‡ | 125‡ | 56‡ | 662‡ | No | RRF, COX-neg | CIV | mtDNA, tRNA-Glu | 4248‡ |
| 66 | F | 7.0 | 10.0† | Alive | Encephalomyopatty, cardiomyopathy | 15.0‡ | 319‡ | 47‡ | 2288‡ | No | RRF, few COX - neg | CI, CIV | mtDNA, tRNA-Leu | 4232‡ |
| 67 | M | 0.1 | 0.1† | Alive | Reversible COX deficiency | 7.5‡ | 118‡ | 64‡ | 193 | No | RRF, COX-neg | CIV | mtDNA, tRNA-Glu | 4161‡ |
| 68 | M | 0.8 | NA | 2 | Psychomotor retardation, epilepsy | 20.0‡ | ND | ND | ND | ND | ND | ND | POLG p.A467T/G848S | 4126‡ |
| 69 | F | 16.0 | NA | 16 | Alpers-Huttenlocher syndrome | 2.8‡ | ND | ND | ND | ND | Critical illness myopathy | ATP 34 nmol/h | POLG c.13399G→A | 3901‡ |
| 70 | M | At birth | 0.2 | Alive | LCHAD crisis, delayed growth decreased liver function | ND | ND | ND | 294‡ | Yes | ND | ND | HADHA c.1528G→C homozygous | 3314‡ |
| 71 | M | At birth | NA | Alive | Severe myopathy | 6.3‡ | ND | ND | ND | ND | Fat droplets | CIV (23%) | Unknown | 3001‡ |
| 72 | M | 7.0 | 13.5† | Alive | Retinitis pigmentosa, short stature | 3.4‡ | 137‡ | 25 | 325‡ | No | RRF, COX-neg | CIV | mtDNA, tRNA-Arg | 2134‡ |
| 73 | F | At birth | NA | Alive | Psychomotor retardation, vision impairment | 4.7‡ | ND | ND | ND | ND | COX-neg general | CI (4%), CIV (19%) | Unknown | 1866‡ |
| 74 | M | 3.0 | 13.8† | Alive | MERRF | 6.4‡ | 84‡ | 76‡ | 229‡ | ND | RRF, COX-neg | CI, CIV | mtDNA, tRNA-Lys | 1612‡ |
| 75 | F | 0.2 | 0.3† | Alive | Reversible COX-deficiency | 3.9‡ | 73‡ | 53‡ | ND | No | RRF, COX-neg | CIV | mtDNA, tRNA-Glu | 1465‡ |
| 76 | M | 0.8 | NA | Alive | Leigh syndrome | 4.3‡ | ND | ND | ND | ND | ND | ND | NDUFS7 | 1335‡ |
| 77 | F | 6.0 | 9.9† | Alive | MELAS | 7.0‡ | 122‡ | 57‡ | 205 | no | RRF, COX-pos | CI | mtDNA, tRNA-Leu | 1090‡ |
| 78 | F | 2.0 | 3.5 | Alive | Alpers’ hepato-encephalopathy, refractoiy epilepsy, psychomotor retardation | ND | 37 | 22 | ND | No | No findings | ND | POLG p.W748S/T914P | 1062‡ |
| 79 | F | 14.0 | 17† | Alive | Mitochondrial myopathy | 5.7‡ | 118‡ | 48‡ | 247‡ | No | RR COX-neg | CI, CIV | mtDNA, tRNA-Phe | 728‡ |
| 80 | F | At birth | NA | Alive | Mitochondrial myopathy, failure to thrive LVH | 5.8‡ | ND | ND | ND | ND | Type I predominance | CI(30%), CIII (13%), CIV (62%) | Unknown | 638‡ |
| 81 | M | 0.8 | NA | Alive | Leigh syndrome | 3.2‡ | ND | ND | ND | ND | Basophilic | CI 70% | mtDNA, 3697G→A | 576‡ |
| 82 | F | At birth | NA | Alive | Psychomotor retardation | 10.5‡ | ND | ND | ND | ND | COX-neg general | CI (16%), CIV (16%) | Unknown | 442‡ |
| 83 | F | At birth | 220 | Alive | Leigh syndrome | 2.6‡ | 38 | 68‡ | ND | ND | No findings | CI | mtDNA, 10191T→C70% | 439‡ |
| 84 | M | At birth | NA | Alive | Psychomotor retardation, PEO | 2.1‡ | ND | ND | ND | ND | RRF, COX-neg | ND | mtDNA deletion | 436‡ |
| 85 | M | 0.5 | 3.3 | Alive | Leigh syndrome | 4.4‡ | 161‡ | 27 | 620‡ | no | COX-neg general | CIV | SURF1 | 335‡ |
| 86 | F | 14.0 | NA | Alive | Severe myopathy | 2.3 | ND | ND | ND | ND | Type I low | CI (7%) | LHON mtDNA, 3460G→A | 116 |
| No severe respiratory chain deficiency or non-mitochondrial disease | ||||||||||||||
| 87 | M | At birth | 2.8 | 3.0 | Progeria, cardiomyopathy, Raynaud’s syndrome, growth retardation | 1.8 | 63 | 29 | 70 | ND | Normal | Normal | LMNC mutation p.L306R | 556‡ |
| 88 | F | At birth | 14.0 | Alive | Smith-Lemly-Opitz syndrome | ND | ND | ND | ND | ND | ND | ND | KCNMA1§ | 89 |
| 89 | F | At birth | NA | Alive | Leigh | 3.3‡ | ND | ND | ND | ND | ND | CII (73%) | Unknown | 76 |
| 90 | F | 3.0 | 11.0 | Alive | Failure to thrive, cardiomyopathy | 3.4‡ | ND | ND | ND | ND | ND | ND | SLC22A5¶ | 65 |
| 91 | M | 0.5 | NA | Alive | Psychomotor retardation | 1.8 | ND | ND | ND | ND | ND | ATP 14 nmol/h | Unknown | 58 |
| 92 | M | 2.0 | 6.0 | Alive | Duchenne muscular dystrophy | ND | ND | ND | 16000‡ | ND | Dystrophy | ND | Deletion in exons 45–50 of DMD | 34 |
| 93 | M | At birth | NA | Alive | Dysmorphia | 0.8 | ND | ND | ND | ND | ND | ATP 22 nmol/h | Unknown | 32 |
| 94 | F | 1.1 | NA | Alive | Psychomotor retardation, epilepsy | 2.0 | ND | ND | ND | ND | ND | ATP 25 nmol/h | Unknown | 22 |
| 95 | M | 0.5 | 16.0 | Alive | Feeding difficulties | 2.7‡ | ND | ND | ND | ND | ND | ND | Gyrate atrophy II | 17 |
| 96 | M | 1.4 | NA | Alive | Failure to thrive | 2.0 | ND | ND | ND | ND | ND | ND | Unknown | 5 |
| 97 | F | 2.0 | NA | Alive | Slight mental retardation | 1.9 | ND | ND | ND | ND | ND | CI (91%) | Unknown | 1 |
| 98 | F | At birth | 10.0 | Alive | Myopathy | ND | ND | ND | ND | ND | ND | ND | Fatty acid oxidation | 0 |
| LCHAD in diet | ||||||||||||||
| 99 | F | At birth | 9.2 | Alive | LCHAD in diet | 1.0 | ND | ND | 437‡ | Yes | ND | ND | HADHA c.1528 G→C homozygous | 185 |
| 100 | F | At birth | 9.0 | Alive | LCHAD in diet, cardiomyopathy | 2.7‡ | ND | ND | 43740‡ | Yes | ND | ND | HADHA c.1528 G→C homozygous | 83 |
| 101 | F | At birth | 0.7 | Alive | LCHAD in diet, delayed growth, cardiomyopathy, mild retinopathy | ND | ND | ND | 390‡ | ND | ND | ND | HADHA c.1528 G→C homozygous | 76 |
CK=creatine kinase. M=male. RRF=ragged red fibre. COX-neg=cytochrome-c-oxidase-negative muscle fibres. CI=respiratory chain complex I deficiency. CIV=respiratory chain complex IV deficiency. mtDNA=mitochondrial DNA. tRNA=transfer RNA. F=female. NA=not available. ND=not determined. ATP=measurement of adenosine triphosphate and phosphocreatine production from pryruvate (reference range 42.1-81.2 nmol/h). MERRF=myoclonic epilepsy with ragged red fibres. MELAS=mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. LVH=left ventricular hypertrophy.
CIII=respiratory chain complex III deficiency. PEO=progressive external ophthalmoplegia. CII=respiratory chain complex II deficiency. LCHAD=long-chain 3 hydroxyacyl CoA dehydrogenase deficiency.
For liver function test results see webappendix p2.
Measured in plasma samples.
Abnormal biomarker values.
Previously SLO.
Also known as OCTN2.