MELAS syndrome and Alpers-Huttenlocher Syndrome (AHS) are both mitochondrial disorders

By SWA

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

FeatureAlpers-Huttenlocher Syndrome (AHS)MELAS Syndrome
InheritanceAutosomal recessiveMitochondrial (maternal inheritance)
Gene InvolvedMost commonly mutations in POLG (nuclear gene encoding mitochondrial DNA polymerase gamma)Most commonly mutations in MT-TL1 (especially the m.3243A>G mutation in mitochondrial DNA)






Age of Onset

AHSMELAS
Typically presents in infancy or early childhoodTypically presents in childhood or early adulthood, but variable






Major Clinical Features

FeatureAHSMELAS
SeizuresSevere, intractable seizures; often status epilepticusSeizures common, often part of stroke-like episodes
Developmental RegressionYes, after initially normal developmentVariable cognitive impairment; can have regression
Liver DysfunctionProminent feature (hepatic failure), often fatalNot a central feature (may occur rarely)
Stroke-like EpisodesNoHallmark feature: stroke-like episodes before age 40
Other SymptomsHypotonia, visual loss, cortical blindnessLactic acidosis, migraine-like headaches, hearing loss, diabetes, myopathy

 

Diagnostic Clues

AHSMELAS
POLG mutation testing, liver biopsy, EEG abnormalitiesmtDNA testing for m.3243A>G, muscle biopsy shows ragged red fibers, elevated lactate in blood/CSF

 

Prognosis

AHSMELAS
Progressive and often fatal in early childhood, especially with liver failureProgressive but more variable; life expectancy depends on severity

 

Summary:

  • AHS: Early-onset, autosomal recessive, associated with POLG mutations, marked by seizures, hepatic failure, and neurodegeneration.

  • 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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