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66 patient data entries in database for mutation G848S.

Entry
#
Mutations
allele 1allele 2
Clinical representationSymptomsAge groupAge of onsetAge of patientAge of deathReference
5G848S1
A143V1
Evidence of maternal inheritance, developmental delay, hypotonia, dementia/encephalopathy, seizures, myoclonic seizures, hepatic failure, elevated transaminases, high CSF lactate, abnormal EEG, leukodystrophy, MRS/lactate peak, abnormal MRI. 71% mtDNA copy number in blood.
-myoclonic seizures
-liver failure
-hypotonic
-encephalopathy
-developmental delay
-dementia
childhood
n/a4n/aTang et al, 2011;

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6G848S1
A143V1
Ataxia, peripheral neuropathy, hearing loss, abnormal MRI, COX deficiency, developmental delay, seizure, delayed gastric emptying, CPK abnormalities, sister died at 2.5 years. 111% mtDNA copy number in blood. Patient II-49.
-movement disorder (ataxia)
-peripheral neuropathy
-developmental delay
-delayed gastric emptying
-CPK abnormalities
-hearing loss
adult
n/a38n/aTang et al, 2011;

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7G848S1
A143V1
Seizures, intractable seizure, abnormal EEG, abnormal MRI. 43% mtDNA copy number in blood.
-intractable seizure
childhood
n/a8n/aTang et al, 2011;

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8G848S1
A143V1
Leigh disease, developmental delay, FTT, abnormal EEG/MRI, hypotonia, seizures, vomiting, hemiplegia, behavior change. 136% mtDNA copy number in muscle and 57% mtDNA copy number in blood.
-hemiparesis
-failure to thrive
-hypotonic
-developmental delay
-vomiting
-leigh syndrome
childhood
n/a4n/aTang et al, 2011;

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15G848S1
R227W4
Born with severe hypotonia, general muscle weakness, hearing loss, GI problems, mild cerbral atrophy, mtDNA depletion in muscle and GI, death via respiratory failure at 20 days.
-muscle weakness
-hypotonic
-GI problems
-respiratory deficiency
-hearing loss
infantile
0.01n/a0.1Giordano et al, 2009;

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21G848S1
R232H4
Hypotonia, microcephaly, abnormal MRI, hepatomegaly, FTT, hypoglycaemia, ptosis. Onset at 6 months with Leighs syndrome and death at 23 months. 3% mtDNA copy number in muscle and 12% mtDNA copy number in liver.
-ptosis
-failure to thrive
-hypotonic
-hepatomegaly
-microcephaly
infantile
0.5n/a2Taanman et al, 2009;

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27G848S1
T251I
P587L2
Ocular bulbar weakness, peripheral neuropathy, muscle weakness, CPEO, ptosis, hypothyroidism, abnormal muscle histology, abnormal muscle ultrastructure, large mitochondrial proliferation, ragged red fibers. 96% mtDNA copy number in blood. Patient II-44.
-peripheral neuropathy
-abnormal muscle histology
-abnormal muscle ultrastructure
-ragged red fibers
-muscle weakness
-ptosis
-PEO
-ocular bulbar weakness
-hypothyroidism
adult
n/a81n/aTang et al, 2011;

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111G848S1
A467T2
Onset at 6 months with FTT, dementia, hypotonia, seizures, hepatopathy, aplasia cutis, delayed myelinisation. Death at 15 months.
-delayed myelination
-failure to thrive
-hypotonic
-dementia
infantile
0.5n/a1.3de Vries et al, 2007;

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112G848S1
A467T2
Alpers, seizures, developmental delay, liver failure, hypotonia, impaired vision, renal stones, mtDNA depletion in muscle. 5% COX deficient fibers.
-liver failure
-hypotonic
-developmental delay
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
0.7n/an/aStewart et al, 2009;

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145G848S1
R627Q5
vomiting, headache, sensory ataxia, areflexia, focal seizures, status epilepticus. MELAS.
-status epilepticus
-focal seizures
-movement disorder (ataxia)
-sensory ataxia
-headache/ migraine
-vomiting
-areflexia
adult
21n/an/aDeschauer et al, 2007;

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147G848S1
R627Q5
At 35 years of age, dysarthria/dysphagia, sensory neuropathy, PEO, distal muscle wasting, phobia anxiety disorder, mild cerebellar atrophy (MRI)
-cerebellar atrophy
-PEO
-dysphagia
-dysarthria
-distal muscle wasting
adult
2935n/aSchulte et al, 2009;

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155G848S1
G746S5
E1143G
Ataxia, PEO, axonal neuropathy, cerebellar atrophy. 3% COX deficient fibers.
-movement disorder (ataxia)
-cerebellar atrophy
-demyelinating neuropathy
-PEO
juvenile
16n/an/aStewart et al, 2009;

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169G848S1
W748S5
E1143G
Onset at 6.5 years with alpers syndrome and death at 7.8 years. 23% mtDNA copy number in liver.
-Alpers syndrome
-encephalopathy
-developmental delay
-epilepsy
childhood
6.5n/a7.8Taanman et al, 2009;

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170G848S1
W748S5
E1143G
Partial status epilepticus, epilepsia partialis, continua, hemiparesis, myoclonus, loss of vision, optical atrophy, pschomotor regression, liver dysfunction, death via pneumonia.
-status epilepticus
-myoclonic seizures
-hemiparesis
-epilepsia partialis
-liver dysfunction
-pschomotor regression
infantile
1n/a11Isohanni et al, 2011;

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171G848S1
W748S5
Headaches/migrains, seizures, intractable seizure, cortical blindness. 32% mtDNA copy number in blood.
-intractable seizure
-headache/ migraine
-cortical blindness
childhood
n/a7n/aTang et al, 2011;

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173G848S1
W748S5
Hypotonia, myoclonus, or myoclonic seizures, intractable seizure, hepatic failure, abnormal EEG. 38% mtDNA copy number in blood.
-myoclonic seizures
-intractable seizure
-liver failure
-hypotonic
childhood
n/a5n/aTang et al, 2011;

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174G848S1
W748S5
Reported as Alpers, onset at 6 years, presenting encephalopathy with epilepsy, hepatopathy absent, and movement disorder (ataxia).
-epilepsy
-movement disorder (ataxia)
-encephalopathy
-Alpers syndrome
-developmental delay
childhood
6n/an/aAshley et al, 2008;

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182R1096C3
G848S1
Developmental delay, hypotonia, dementia/encephalopathy, exercise intolerance, muscle weakness, easy fatigability, ptosis, GI reflux, delayed gastric emptying, cyclic vomiting, hepatic failure, elevated transaminases, lactic acidosis, short statue, FTT. 53% mtDNA copy number in blood.
-lactic acidosis
-muscle weakness
-exercise intolerance
-ptosis
-liver failure
-failure to thrive
-hypotonic
-encephalopathy
-developmental delay
-dementia
-vomiting
-GI reflux
-cyclic vomiting
-delayed gastric emptying
infantile
n/a2n/aTang et al, 2011;

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183P1073L3
G848S1
pschomotor delay, seizures, liver disease, GI dysmotility, lactic acidosis.
-lactic acidosis
-liver dysfunction
-GI dysmotility
infantile
0.4n/a0.9Kurt et al, 2010;

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184P1073L3
G848S1
Hypotonia, FTT, gastro-oesophaeal reflux. 36% mtDNA copy number in muscle, 62% mtDNA copy number in blood.
-failure to thrive
-hypotonic
infantile
n/a2n/aTang et al, 2011;

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185G848S1
G848S1
Seizures, SIDS/unexplained death, MRS/lactate peak, abnormal MRI, abnormal respiratory enzymes. 7% mtDNA copy number in muscle.
-no known symptoms
childhood
n/a5n/aTang et al, 2011;

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237W748S5
E1143G
G848S1
hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion, microvesicular steatosis.
-liver failure
-hepatocerebral
-developmental delay
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
0.1n/a0.9Davidzon et al, 2005;

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250G848S1
T251I
P587L2
PEO, severe ophthalmoplegia and ptosis, which appeared insidiously and had been present clinically since the age of 55. Muscle biopsy at age 68 revealed mitochondrial myopathy, as well as muscle inflammation with granulomas. multiple mtDNA deletions in muscle tissue.
-myopathy
-mitochondrial myopathy
-ptosis
-PEO
-ophthalmoplegia
adult
5575n/aKollberg et al, 2005;

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252W748S5
E1143G
G848S1
hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion
-liver failure
-hepatocerebral
-developmental delay
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
0.7n/a2.5Davidzon et al, 2005;

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253W748S5
E1143G
G848S1
hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion, microvesicular steatosis,
-liver failure
-hepatocerebral
-developmental delay
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
1n/a6.5Davidzon et al, 2005;

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255W748S5
E1143G
G848S1
hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, microvesicular steatosis, fibrosis
-liver failure
-hepatocerebral
-developmental delay
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
0.3n/a1Davidzon et al, 2005;

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257W748S5
E1143G
G848S1
Refractory seizures, psychomotor regression, liver disease, presenting symptom was status epilepticus, Transient hypoglycemia, Transient lactic acidemia
-lactic acidosis
-status epilepticus
-intractable seizure
-liver dysfunction
-hypoglycemia
infantile
1n/a1.7Nguyen et al, 2005;

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259A467T2
G848S1
Refractory seizures, psychomotor regression, liver disease, presented with liver failure
-intractable seizure
-liver failure
-liver dysfunction
infantile
1n/a1.3Nguyen et al, 2005;

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260A467T2
G848S1
Refractory seizures, psychomotor regression, liver disease, Transient hypoglycemia, Transient lactic academia, Elevated CSF protein, presented with epilepsia partialis continua,
-intractable seizure
-epilepsia partialis
-liver dysfunction
-hypoglycemia
infantile
0.9n/a1.8Nguyen et al, 2005;

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287G848S1
W748S5
Developemental delay, status epilepticus onset at 6 years 7 months, valproic acid therapy 6 weeks, liver failure with transplant, epilepsia partialis continua, elevated CSF lactate, elevated CSF protein, mtDNA depletion in liver
-status epilepticus
-epilepsia partialis
-liver failure
infantile
6.67.8n/aWolf et al, 2009;

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288G848S1
W748S5
status epilepticus onset epilepsia partialis continua, elevated CSF lactate, elevated CSF protein,
-status epilepticus
-epilepsia partialis
childhood
10.67n/a11.5Wolf et al, 2009;

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311G848S1
A467T2
Cyclic vomiting, episodic hypoglycemia then seizure onset at 6 years, generalized seizures, GI dysmotility, eyelid ptosis,ophthalmoplegia, sensorineural hearning loss, absent smooth pursuit eye movements
-ptosis
-ophthalmoplegia
-GI dysmotility
-vomiting
-cyclic vomiting
-hypoglycemia
childhood
611n/aSaneto et al, 2010;

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312G848S1
W748S5
seizure onset at 2 years, complex partial seizure and epilepsia partialis continua myoclonus, Truncal ataxia, intention tremor
-myoclonic seizures
-epilepsia partialis
-movement disorder (ataxia)
-tremor
infantile
24n/aSaneto et al, 2010;

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313G848S1
T251I
P587L2
progressively droopy eyelids, double vision, gait instability, proximal arm weakness, ragged red and ragged blue (succinate dehydrogenase–positive) fibers in about 3% and 6% of all muscle fibers, bilateral ptosis, diplopia, dysarthria, myopathy involving the facial muscles, sensory ataxic polyneuropathy
-polyneuropathy
-ragged red fibers
-myopathy
-ptosis
-diplopia
-dysarthria
adult
n/a80n/aWeiss and Saneto, 2010;

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316G848S1
W748S5
Myoclonic Seizures, Generalized tonic-clonic seizures, Focal motor seizures, Epilepsia partialis continua, Developmental Delay or Regression, ataxia, Abnormal Liver Enzymes, Serum Lactate, liver mtDNA depletion, Alpers
-myoclonic seizures
-epilepsia partialis
-movement disorder (ataxia)
-developmental delay
-Alpers syndrome
-encephalopathy
infantile
2n/a6.33Hunter et al, 2011;

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317G848S1
W748S5
Myoclonic Seizures, Generalized tonic-clonic seizures, Focal motor seizures, Epilepsia partialis continua, Developmental Delay or Regression, ataxia, Abnormal Liver Enzymes, Serum Lactate, Alpers
-myoclonic seizures
-epilepsia partialis
-movement disorder (ataxia)
-developmental delay
-Alpers syndrome
-encephalopathy
childhood
6n/a6.75Hunter et al, 2011;

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318G848S1
A467T2
Myoclonic Seizures, Epilepsia partialis continua, Developmental Delay or Regression, ataxia, Abnormal Liver Enzymes, Serum Lactate, liver mtDNA depletion, Alpers
-myoclonic seizures
-epilepsia partialis
-movement disorder (ataxia)
-developmental delay
-Alpers syndrome
-encephalopathy
infantile
0.5n/a3.33Hunter et al, 2011;

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319G848S1
A467T2
Myoclonic Seizures, Generalized tonic-clonic seizures, Focal motor seizures, Developmental Delay or Regression, hypotonia, tremor, Abnormal Liver Enzymes, Serum Lactate, liver mtDNA depletion, death by liver failure, Alpers
-myoclonic seizures
-liver failure
-hypotonic
-developmental delay
-Alpers syndrome
-tremor
-encephalopathy
-epilepsy
infantile
0.83n/a0.92Hunter et al, 2011;

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328G848S1
A467T2
focal seizures, elevated liver transaminases, Elevated CSF protein, patient died several weeks later
-focal seizures
infantile
0.8n/a1McCoy et al, 2011;

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336R227W4
G848S1
Complex I deficiency, Hypotonia, lethargy, respiratory distress, metabolic acidosis, FTT, encephalopathy
-failure to thrive
-hypotonic
-encephalopathy
infantile
0.010.06n/aCalvo et al, 2012;

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345G848S1
A467T2
presented with hypoglycemia, lactic acidosis, moderate ketosis and liver dysfunction, generalized hypotonia, progressive jaundice and abdominal distension with ascites, status epilepticus with generalized tonico-clonic seizures. She had an intermittent tremor, moderate truncal ataxia with a wide-based gait, myoclonic seizures, epilepsia partialis continua,
-lactic acidosis
-status epilepticus
-myoclonic seizures
-epilepsia partialis
-movement disorder (ataxia)
-liver dysfunction
-jaundice
-hypotonic
-ketosis
-hypoglycemia
-tremor
infantile
0.29n/a5Scalais et al, 2012;

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359G848S1
G746S5
CPEO, peripheral neuropathy, ataxia, dysarthria, COX-deficient fibers, presence of mitochondrial dna deletions in muscle, Severe sensory and moderate motor neuronopathy, Distal and proximal neurogenic change
-movement disorder (ataxia)
-peripheral neuropathy
-PEO
-dysarthria
adult
2636n/aLax et al, 2012a;

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408G848S1
A467T2
Delayed motor and mental development, From the age of 3 years his psychomotor development declined and epilepsy, visual impairment and sensorineuronal deafness, epilepsia partialis continua. Bilateral ptosis, generalized hypotonia, ataxia, absent reflexes and hyperlaxity by age 5.
-epilepsy
-epilepsia partialis
-movement disorder (ataxia)
-ptosis
-hypotonic
infantile
35n/ade Vries et al, 2008;

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438G848S1
T251I
CPEO, multiple mtDNa deletions.
-PEO
adult
45n/an/aRouzier et al, 2013;

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447G848S1
A467T2
Alpers, status epilepticus and somnolence, ataxia with dysmetria and muscular hypotonia. Healthy unrelated parents. Laboratory investigations revealed myoclonic epilepsy with ragged red fibers,
-status epilepticus
-epilepsy
-movement disorder (ataxia)
-ragged red fibers
-hypotonic
-Alpers syndrome
-encephalopathy
-developmental delay
infantile
2.23.55.5Hasselmann et al, 2010;

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470G848S1
A467T2
Epilepsy, stroke-like episodes.
-epilepsy
-stroke
-stroke-like episodes
infantile
0.6n/a0.6Tzoulis et al, 2013;

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478G848S1
Q497H2
W748S5
E1143G
The index patient presented at the age of 8 months with microcephaly, seizures, and developmental delay. From the time of the first observation she rapidly developed epilepsia partialis continua, multifocal myoclonic jerks, and progressive psychomotor retardation. MRI performed at 8 months was generally unremarkable. By 9 months of age the brain MRI showed signifi cant changes including a diffuse severe cerebral and cerebellar atrophy involving gray and white matter.
-epilepsia partialis
-cerebellar atrophy
-developmental delay
-retardation
-microcephaly
infantile
n/a0.61Brunetti-Pierri et al, 2008;

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479G848S1
Q497H2
W748S5
E1143G
He exhibited a very similar phenotype to his sister, with a catastrophic onset of intractable seizures at the age of 9 months, progressive encephalopathy with epilepsia partialis continua and myoclonic jerks, and developmental regression. MRI imaging was not performed.
-intractable seizure
-epilepsia partialis
-encephalopathy
infantile
0.51.25n/aBrunetti-Pierri et al, 2008;

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480G848S1
Q497H2
W748S5
E1143G
He exhibited a very similar phenotype to his sister, with a catastrophic onset of intractable seizures at the age of 9 months, progressive encephalopathy with epilepsia partialis continua and myoclonic jerks, and developmental regression. MRI imaging was not performed.
-intractable seizure
-epilepsia partialis
-encephalopathy
infantile
0.51.25n/aBrunetti-Pierri et al, 2008;

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517S1104C1
G848S1
Ataxia, Dementia, Peripheral neuropathy, Areflexia, Myopathy, fatigue, depression, Ophthalmoplegia, Dysarthria, Osteoporosis, arPEO.
-movement disorder (ataxia)
-peripheral neuropathy
-myopathy
-PEO
-ophthalmoplegia
-dementia
-dysarthria
-areflexia
adult
2259n/aLax et al, 2012b;

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521G848S1
A467T2
Alpers, Epilepsy, developmental delay, COX deficient fibres.
-epilepsy
-developmental delay
-Alpers syndrome
-encephalopathy
infantile
1n/an/aStewart et al, 2009;

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529G848S1
A467T2
mtDNA depletion. severe hypoglycemia, liver biopsy shows micronodular cirrhosis. At 3 y 9 m, status epilepticus develops which occurs again at 4 y and is difficult to control. myoclonia. She dies from bronchopulmonary infection when 5 y old. COX negative fibers.
-status epilepticus
-hypoglycemia
infantile
0.2545Roels et al, 2009;

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542G848S1
A467T2
Ragged Red Fibers, COX-Deficient Fibers. The boy had feeding difficulties with failure to thrive since 3 months of age. Delayed motor development. general muscle weakness and ataxia. compromised liver function.
-movement disorder (ataxia)
-ragged red fibers
-muscle weakness
-failure to thrive
infantile
0.33n/a1.33Kollberg et al, 2006;

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559G848S1
A467T2
Epilepsy, stroke-like episode.
-epilepsy
-stroke
infantile
0.6n/a0.6Tzoulis et al, 2014;

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574G848S1
S1104C1
The patient first presented at the age of 22 years with left-sided ptosis, which slowly progressed over the next 20 years to an almost complete ophthalmoplegia. He developed proximal muscle weakness at age 50 and his first Parkinsonian features at age 51. rigidity, tremor, bradykinesia and difficulty performing fine motor tasks. Proximal myopathy. sensorimotor neuropathy. Dysphagia.
-muscle weakness
-myopathy
-ptosis
-ophthalmoplegia
-dysphagia
-tremor
adult
225759Betts-Henderson et al, 2009;

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604G848S1
T251I
P587L2
PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle.
-ragged red fibers
-cox-negative
-PEO
adult
n/an/an/aLamantea et al, 2002;

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629G848S1
A467T2
Developmental delay, dementia, seizures, Alpers, Ataxia
-movement disorder (ataxia)
-developmental delay
-dementia
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
2n/an/aWong et al, 2008;

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630G848S1
A467T2
Developmental delay, dementia, seizures, Alpers, Lactic acidosis, Stroke
-lactic acidosis
-stroke
-developmental delay
-dementia
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
2n/an/aWong et al, 2008;

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631G848S1
A467T2
Developmental delay, dementia, seizures, Alpers, Lactic acidosis, Cortical athrophy, hypoglycemia
-lactic acidosis
-developmental delay
-dementia
-Alpers syndrome
-hypoglycemia
-encephalopathy
-epilepsy
infantile
1.5n/an/aWong et al, 2008;

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632G848S1
A467T2
Developmental delay, dementia, seizures, Alpers, Stroke, ataxia, exercise intolerance
-movement disorder (ataxia)
-exercise intolerance
-stroke
-developmental delay
-dementia
-Alpers syndrome
-encephalopathy
-epilepsy
childhood
9n/an/aWong et al, 2008;

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633G848S1
A467T2
Developmental delay, dementia, seizures, Alpers, hypotonia, failure to thrive
-failure to thrive
-hypotonic
-developmental delay
-dementia
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
0.8n/an/aWong et al, 2008;

[view data]

634G848S1
A467T2
Developmental delay, dementia, seizures, Alpers
-developmental delay
-dementia
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
2n/an/aWong et al, 2008;

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639G848S1
T251I
P587L2
Alpers
-Alpers syndrome
-encephalopathy
-developmental delay
-epilepsy
infantile
0.5n/an/aWong et al, 2008;

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641G848S1
Q497H2
W748S5
E1143G
developmental delay, dementia, seizures, Alpers, Family history of Alpers syndrome.
-developmental delay
-dementia
-Alpers syndrome
-encephalopathy
-epilepsy
infantile
1n/an/aWong et al, 2008;

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689G848S1
A467T2
Hepatopathy, Epilepsy, Hepatopathy,
-epilepsy
infantile
1.5n/an/aAshley et al, 2008;

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702G848S1
A467T2
He developed normally in the first 6 months. Refusal of food and failure to thrive were noted from the 7th month of life. At 1 year of age, increased transaminase levels in the blood were accompanied by liver enlargement and hyperecogenicity. Motor development was delayed. hypoglycaemic episodes and lactic acidosis. A liver biopsy at the age of 16 months revealed steatosis and fibrosis. At 20 months of age, he had numerous episodes of status epilepticus and epilepsia partialis continua. The patient died at 2.5 years of age during an episode of status epilepticus. Alpers’ syndrome.
-lactic acidosis
-status epilepticus
-epilepsia partialis
-failure to thrive
-Alpers syndrome
-encephalopathy
-developmental delay
infantile
0.5n/a2.5Ferrari et al, 2005;

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1-5 pathogenic cluster assignment of mutations. Mutations displayed without a superscript number are outside of the assigned pathogenic clusters. See cluster definitions for details.

Number of displayed patient cases: 66
Avg age of onset in displayed cases: 8.6
Std dev in onset in displayed cases: 16.9

Search criteria for patient entries:
Mutations Entry IDs Clusters Reference Residue range
Mutations:
Allele 1:Allele 2:
Separate multiple mutations with commas.
Use "PNF" for non-missense mutations.
Match: Inclusive Exact
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