Alpers' disease: Difference between revisions
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==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
*Prognosis is generally poor, | *Prognosis is generally poor, | ||
*Common complications of Alpers disease include [[seizures]], [[liver failure]] poor growth, infection-associated [[encephalopathy]], increased muscle tone, [[gastrointesinal dysfunction]], [[dilated cardiomyopathy]], [[dementia]], [[cortical blindness]], [[spasticity]], [[jaundice]] and/or [[ascites]]. | |||
==Diagnosis== | ==Diagnosis== | ||
Revision as of 19:28, 27 August 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[3]
Synonyms and keywords: Alpers-Huttenlocher Syndrome, Progressive Infantile Poliodystrophy, Mitochondrial Deoxyribonucleic acid (DNA) depletion syndrome-4A
Overview
Alpers' disease is an autosomal recessive genetic syndrome characterized by seizures, hepatopathy, and progressive cognitive impairment. It is caused by mutation in the POLG gene resulting in mitochondrial DNA depletion.
Classification
- There is no established system for the classification of Alpers disease.
Pathophysiology
- Alpers disease is inherited in an autosomal recessive pattern.
- Mutation in POLG1 gene reduces polymerase gamma functionality resulting in defective mitochondrial DNA replication and causing depletion of mitochondrial DNA. [1]
- Brain, liver and skeletal muscles are most involved due to high number of mitochondria.[2]
Causes
- Alpers disease is a mitochondrial disorder caused by a mutation in the POLG1 gene.[3]
Differentiating Alpers disease from other Diseases
- Alpers disease must be differentiated from other mitochondrial diseases caused POLG gene mutation:
- Childhood Myocerbrohepatopathy Spectrum Disorder[4]
- Myoclonus epilepsy myopathy sensory ataxia (MEMSA)
- Progressive external ophthalmoplegia[5]
Epidemiology and Demographics
- The prevalence of Alpers disease is approximately 1 per 100,000 individuals worldwide.
- Alpers disease affects men and women equally.
- Higher carrier frequency is seen in the Northern European population.[2]
Risk Factors
- There are no established risk factors for Alpers disease.
Screening
- There is insufficient evidence to recommend routine screening for Alpers disease.
Natural History, Complications, and Prognosis
- Prognosis is generally poor,
- Common complications of Alpers disease include seizures, liver failure poor growth, infection-associated encephalopathy, increased muscle tone, gastrointesinal dysfunction, dilated cardiomyopathy, dementia, cortical blindness, spasticity, jaundice and/or ascites.
Diagnosis
Diagnostic Study of Choice
History and Symptoms
- Alpers disease has a bimodal age of onset. The majority cases present in first two years of life and the rest present between the ages of 2 and 25.[6]
- Alpers disease is characterized by a triad of refractory seizures, psychomotor regression and hepatopathy.
- Other symptoms may include vision changes, migraines, hallucinations, cognitive impairment, depression, anxiety and/or ataxia.[7]
Physical Examination
- Common physical examination findings of Alpers disease include spasticity, ataxia, altered muscle tone.
- Other physical findings include poor growth, developmental delay, failure to thrive, and/or vision changes.
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography or Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
- There is no treatment for Alpers disease and no way to slow its progression; the mainstay of therapy is supportive and palliative care.
- Seizure management should be achieved by with drugs with newer generation drugs(lamotrigine, primidone, topiramate, oxcarbazepine) with low hepatic impact.
- Valproic acid should be avoided for seizure management as it can worsen liver disease.[8]
- Physical therapy may help relieve spasticity.
- Occupational/speech therapies may also help with neurological deficits.
- Tracheostomy, gastric feeding tube, and/or artificial ventilation may be helpful once the disease progresses.[9]
Surgery
- Surgical intervention is not recommended for the management of Alpers disease.
Primary Prevention
- There are no established measures for the primary prevention of Alpers disease.
Secondary Prevention
- There are no established measures for the secondary prevention of Alpers disease.
Notes
- ↑ Copeland WC (2012). "Defects in mitochondrial DNA replication and human disease". Crit Rev Biochem Mol Biol. 47 (1): 64–74. doi:10.3109/10409238.2011.632763. PMC 3244805. PMID 22176657.
- ↑ 2.0 2.1 Saneto RP, Cohen BH, Copeland WC, Naviaux RK (2013). "Alpers-Huttenlocher syndrome". Pediatr Neurol. 48 (3): 167–78. doi:10.1016/j.pediatrneurol.2012.09.014. PMC 3578656. PMID [1] 23419467]] Check
|pmid=value (help). - ↑ Qian Y, Ziehr JL, Johnson KA (2015). "Alpers disease mutations in human DNA polymerase gamma cause catalytic defects in mitochondrial DNA replication by distinct mechanisms". Front Genet. 6: 135. doi:10.3389/fgene.2015.00135. PMC 4391263. PMID 25914719.
- ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301791.
- ↑ Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C; et al. (2008). "Molecular and clinical genetics of mitochondrial diseases due to POLG mutations". Hum Mutat. 29 (9): E150–72. doi:10.1002/humu.20824. PMC 2891192. PMID 18546365.
- ↑ Hayhurst, Hannah; Anagnostou, Maria‐Eleni; Bogle, Helen J.; Grady, John P.; Taylor, Robert W.; Bindoff, Laurence A.; McFarland, Robert; Turnbull, Doug M.; Lax, Nichola Z. (2018). "Dissecting the neuronal vulnerability underpinning Alpers' syndrome: a clinical and neuropathological study". Brain Pathology. 29 (1): 97–113. doi:10.1111/bpa.12640. ISSN 1015-6305.
- ↑ Saneto RP (2016). "Alpers-Huttenlocher syndrome: the role of a multidisciplinary health care team". J Multidiscip Healthc. 9: 323–33. doi:10.2147/JMDH.S84900. PMC 4968991. PMID 27555780.
- ↑ Saneto RP, Cohen BH, Copeland WC, Naviaux RK (2013). "Alpers-Huttenlocher syndrome". Pediatr Neurol. 48 (3): 167–78. doi:10.1016/j.pediatrneurol.2012.09.014. PMC 3578656. PMID 23419467.
- ↑ Giordano C, Sebastiani M, De Giorgio R, Travaglini C, Tancredi A, Valentino ML; et al. (2008). "Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion". Am J Pathol. 173 (4): 1120–8. doi:10.2353/ajpath.2008.080252. PMC 2543079. PMID 18787099.
References
"Alpers' Disease Information Page". (Website). National Institute of Neurological Disorders and Stroke, U.S. National Institutes of Health.