Table 1.

Comparison of published cases with FASTKD2-related mitochondrial disease (FASTKD2-MD).

	Patient 1 Ghezzi et al. (11)	Patient 2 Ghezzi et al. (11)	Patient 3 Yoo et al. (10)	Patient 4 Wei et al. (12)	Patient 5 Wei et al. (12)	Patient 6 Wei et al. (12)	Patient 7 Astner-Rohracher et al. (19)
FASTKD2 mutation	Homozygous non-sense mutation in the KIAA0971 gene p.R416X + p.R416X	Homozygous non-sense mutation in the KIAA0971 gene p.R416X+ p.R416X	Compound heterozygous mutations p.R205X (c.613C>T) + p.L255P (c.764T>C)	Homozygous mutation at p.L270fs*11 (c.808_809insTTTCAG TTTTG)	Homozygous mutation p.R290 (c.868C>T)	Two compound heterozygous mutations at c.1859delT/c.868C>T and p.S621Lfs*14/p.R290	Homozygous mutation p.[Arg358Ter]; [Arg358Ter] (c.[1072C>T]; [1072C>T])
Ethnics/nationality	Bedouin (Israel) sister	Bedouin (Israel) Brother	Korean	Chinese	Chinese	Chinese	Austrian
Consanguinity	Yes (first degree cousins)	Yes (first degree cousins)	No	No	Yes	No	No
Sex	Female	Male	Male	Female	Female	Female	Male
Age at disease onset	7 months	1 year	15 years	6 months	22 months	1 year	14 years
First symptom	Fever associated seizure	Fever associated subacute neurological deterioration (Muscle hypotonia, extrapyramidal movements left>right)	Generalized tonic clonic seizure	Axial hypotonia + dyskinesia	Seizure	Seizure	Focal to bilateral tonic clonic seizure -> refractory SE (NORSE)
Developmental delay	Delayed development from age 7 months, at age 14 y: follows simple commands, 20 words vocabulary, can sit, is not able to walk	Deterioration of neurological development from age 1 year, at 4 years bed-ridden with neither communication nor any voluntary activity.	No	Delayed motor development, able to sit at the age of 9 months, walks at the age of 3	Yes, no further information given	Delayed development from the beginning, unable to sit until 7 months and walk until 22 months of age	No
Status epilepticus (SE)	No	Repeated SE	1st SE at age 18 y, 2nd SE at age 26 y	No	No epilepsy	No	Refractory SE at age 14 y and age 21 y
Clinical manifestations	Developmental delay, Myoclonic and gelastic seizures, optic atrophy, spastic left-sided hemiparesis	Developmental delay, refractory seizures with repeated SE, optic atrophy, muscle hypotonia, extrapyramidal symptoms	Stroke-like episode with visual field deficit left, epilepsy, Bilateral optic atrophy	Developmental delay, axial hypotonia, dyskinesia	Dyskinesia, unconscious shaking of hands, occasional convulsions at 3 years	Nystagmus, hypotonia, slurred speech, diminished deep tendon reflexes in the lower limbs.	Refractory status epilepticus twice, drug-resistent focal epilepsy, mild psychomotor slowing, myopathy, spastic atactic gait
Brain MRI	MRI at age 7 months: Generalized Symmetric atrophy CT at age 5y: Right hemispheric atrophy	MRI at age 1 y: Hyperintensity left nucleus caudatus, globus pallidus, and crus cerebri CT at age 2.5 y: Generalized atrophy, more pronounced on the left basal ganglia, bilateral dilatation of ventricles + basal cysternae	Right occipital lobe infarction	MRI at age 14 months:high T2 signal intensity in bilateral globus pallidus, medulla oblongata, and mesencephalon	MRI at age 9 years:bilateral symmetrical hyperintensity in globus pallidus	MRI at age 1 year 8 months:Brain atrophy, bilateral symmetrical hyperintensity signals in globus pallidus, putamen, and caudate nucleus MRI at age 2.5 years: T2 hyperintensity bilateral basal ganglia and cerebral atrophy	MRI at age 14 years: Diffusion restriction and FLAIR hyperintensity right temporo-occipital MRI at age 22 years: atrophy right temporo-parietal
EEG	Bilateral epileptiform discharge left > right	Right hemispheric attenuation + triphasic waves over left hemisphere	Slowing right hemisphere, sharp transients right parieto-occipital region	Not performed	Abnormal (not specified)	Not reported	Bilateral synchronous spike and wave with right posterior maximum
Lactate level	Serum 2.4–3.2 mM (normal < 1.8 mM)	CSF 3.8 mM (normal < 1.8 mM),	Serum 2.2 mM (normal < 1.6 mM)	Serum 3.4 mM (normal < 2.1 mM)	Normal: 1.9 mM (normal < 2.1 mM)	Serum 6.3 (normal < 2.1 mM)	Serum 2.2 mmol/l CSF 2.2 mmol/l (normal 1.1–2.2 mmol/l)
Abdominal sonography	Normal	Normal	Normal	Not performed, laboratory testing normal	Not reported	Not reported	Normal
Renal function	Normal	Normal	Normal	Normal	Not reported	Not reported	Normal
Specific therapy	Not reported	Not reported	Coenzyme Q10	Not reported	Not reported	Not reported	Coenzyme Q10
Echocardiography	Normal	Normal	Normal	Not reported	Hypertrophic cardiomyopathy, sinus tachycardia	Not reported	Normal
Optic nerve	Bilateral opticatrophy	Bilateral opticatrophy	Bilateral opticatrophy	Not reported	Not reported	Not reported	Bilateral mild atrophy of temporal fibers
Muscle biopsy	COX activity reduced to 21% of controls, other respiratory chain complexes: normal	Not performed	SDH, COX, mGT stain: normal	Not performed	Not performed	Not performed	COX, citrate synthase, respiratory chain complexes I, II, III, V: normal
Skin fibroblasts	Normal activity of MRC	Normal activity of MRC					OCR: no decrease of basal or maximal respiration
Immortalizedlym phozytes	Not performed	Decreased COX activity		16s-rRNA 30% lower compared to controls; 8.5-fold higher extracellular lactate generation	16s- rRNA 54% lower compared to controls; 4.3-fold higher extracellular lactate generation	Not performed	Not performed
Visual evoked potentials	Not performed	Not performed	Delayed	Not performed	Not performed	Not performed	Not performed

COX, cytochrome C oxidase; mGT, modified Gomori trichrome; MRC, mitochondrial respiratory chain complex; NORSE, new-onset refractory status epilepticus; OCR, oxygen consumption rate; SE, status epilepticus; SDH, succinate dehydrogenase.