MELAS syndrome and Alpers-Huttenlocher Syndrome (AHS) are both mitochondrial disorders
Alpers-Huttenlocher Syndrome (AHS) and MELAS syndrome are both rare, progressive mitochondrial disorders that affect the nervous system and other organs. Despite sharing a common origin in mitochondrial dysfunction, they differ markedly in their genetic causes, clinical presentation, and age of onset. AHS typically presents in early childhood and is characterized by intractable seizures, developmental regression, and liver failure, often linked to mutations in the nuclear POLG gene.
In contrast, MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) usually manifests later in childhood or early adulthood and is caused by mitochondrial DNA mutations, most commonly the m.3243A>G mutation in the MT-TL1 gene. Some live for years without any symptoms.
Understanding the distinctions between these two syndromes is essential for accurate diagnosis, appropriate genetic counseling, and tailored management strategies.
But they differ significantly in their genetic causes, clinical features, and typical onset. Here's a clear comparison:
Genetic Cause
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Age of Onset
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Major Clinical Features
Feature | AHS | MELAS |
---|---|---|
Seizures | Severe, intractable seizures; often status epilepticus | Seizures common, often part of stroke-like episodes |
Developmental Regression | Yes, after initially normal development | Variable cognitive impairment; can have regression |
Liver Dysfunction | Prominent feature (hepatic failure), often fatal | Not a central feature (may occur rarely) |
Stroke-like Episodes | No | Hallmark feature: stroke-like episodes before age 40 |
Other Symptoms | Hypotonia, visual loss, cortical blindness | Lactic acidosis, migraine-like headaches, hearing loss, diabetes, myopathy |
Diagnostic Clues
AHS | MELAS |
---|---|
POLG mutation testing, liver biopsy, EEG abnormalities | mtDNA testing for m.3243A>G, muscle biopsy shows ragged red fibers, elevated lactate in blood/CSF |
Prognosis
AHS | MELAS |
---|---|
Progressive and often fatal in early childhood, especially with liver failure | Progressive but more variable; life expectancy depends on severity |
Summary:
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AHS: Early-onset, autosomal recessive, associated with POLG mutations, marked by seizures, hepatic failure, and neurodegeneration.
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MELAS: Later-onset, mitochondrial inheritance, caused by mtDNA mutations, marked by stroke-like episodes, seizures, and lactic acidosis.
References:
MELAS https://www.ncbi.nlm.nih.gov/books/NBK1233/
and https://www.orpha.net/en/disease/detail/550
and https://my.clevelandclinic.org/health/diseases/25149-melas-syndrome
Alpers-Huttenlocher
Syndrome: A Rare and Devastating Mitochondrial Disorder
https://swaresearch.blogspot.com/2025/01/alpers-huttenlocher-syndrome-rare-and.html
© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742
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