At a Glance

compare MELAS vs MIDD

Understanding what the names mean, where symptoms overlap, and how CPEO fits in.

event Editorial update September 2026
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MELAS vs MIDD - quick summary

MELAS

MELAS includes stroke-like episodes and variable neurological and other organ problems. It can begin at different ages. MELAS requires a stroke-like episode and has variable encephalomyopathic and multisystem manifestations. 12

MIDD

MIDD combines diabetes and hearing loss, often in adulthood. It can also involve other organs and should not automatically be called mild. MIDD is a mitochondrial diabetes/hearing phenotype with variable onset and multisystem burden. 3

CPEO & other patterns

Other patterns include drooping eyelids and limited eye movements, muscle symptoms, or mixed features. These are not fixed stages between MIDD and MELAS. CPEO, myopathic, non-syndromic and overlap phenotypes occur; labels do not define a linear severity scale. 45

Useful next steps

Discuss appropriate testing, monitoring and medicine review with your team. Individualise molecular investigation, organ surveillance and medication review. 6789

Explanation

Different names, overlapping experiences

If you have been reading about m.3243A>G, you have probably come across both MIDD and MELAS. It is easy to wonder whether they are two names for the same thing. Both can be caused by this DNA change, and there is a lot of overlap, but the names describe different patterns of symptoms. MIDD and MELAS can both be manifestations of m.3243A>G. They describe distinct clinical syndromes within an overlapping spectrum, rather than interchangeable diagnoses. 45

MIDD stands for maternally inherited diabetes and deafness: diabetes and hearing loss are its main features. MELAS stands for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. The key distinction is the occurrence of stroke-like episodes. Someone with MELAS may also have diabetes and hearing loss, so their experience can overlap with MIDD. MIDD describes maternally inherited diabetes and deafness. MELAS describes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes; a stroke-like episode is required for the MELAS diagnosis. Diabetes and sensorineural hearing loss may occur in MELAS, and overlap phenotypes are recognised. 12345

The overlap goes beyond the symptoms in the names. Fatigue, muscle weakness, digestive difficulties and problems affecting the heart or kidneys can be part of m.3243A>G disease. You may have some of these features without fitting neatly into either MIDD or MELAS, and having one diagnosis does not mean you will develop every symptom associated with it. Fatigue, myopathy, gastrointestinal dysfunction, cardiomyopathy and renal involvement occur across the m.3243A>G spectrum. Syndromic labels do not capture every combination of manifestations or predict all future organ involvement. 45717

CPEO is another pattern you may come across. The full name, chronic progressive external ophthalmoplegia, describes a gradual weakening of the muscles that move the eyes, making eye movements more limited. The eyelids may also droop, and some people have weakness in other muscles. CPEO can occur alongside features of MIDD or MELAS; it is not a stage in between the two. Chronic progressive external ophthalmoplegia (CPEO) involves progressive limitation of eye movements, often with ptosis and sometimes with more general myopathy. m.3243A>G can cause CPEO or overlap syndromes involving MIDD or MELAS. These labels do not form a sequence of disease stages. 45

These names also do not tell you how much support someone needs. MIDD can affect much more than hearing and blood sugar, while the effects of MELAS vary from person to person. The label is a starting point for understanding your health, rather than a complete picture of it. Neither syndrome label is a complete measure of disease burden. MIDD can involve multiple organs, and MELAS has variable neurological and systemic severity. 2312

MELAS and MIDD side by side

Read this as a guide to the patterns behind the names. For more detail, see the MELAS guide or MIDD guide.

Symptoms and care in MELAS and MIDD associated with m.3243A>G
Feature bolt MELAS hearing MIDD
Typical onset Childhood or adulthood Any age, including onset after 40 12 Often adulthood; varies Frequently adult onset; variable 3
Hearing loss Can occur Sensorineural loss may occur 1314 Core feature; timing varies Characteristic sensorineural loss; variable chronology 3
Diabetes Can occur Mitochondrial diabetes may coexist 3 Core feature Characteristic mitochondrial diabetes 3
Stroke-like episodes Required for the MELAS label Required by current syndrome definition 12 Would prompt reassessment for overlap An episode prompts phenotypic reassessment 2
Seizures May occur during or between episodes Epilepsy is a recognised manifestation 12 Possible; not a defining feature Possible in the broader m.3243A>G phenotype 45
Lactic acid build-up May occur; needs assessment Hyperlactataemia/acidosis requires interpretation 12 Variable Biochemical expression varies 12
Migraine Can occur Migraine-like headache can occur 12 Can occur Migraine can occur 510
Muscle weakness Weakness and low stamina may occur Myopathy and exercise intolerance 12 Weakness and low stamina may occur Variable myopathic features 510
Eyes Episodes may affect vision Cortical visual disturbance during episodes 215 Retinal changes may occur Macular pattern dystrophy may occur 716
Brain MRI May show changing stroke-like lesions Evolving non-territorial stroke-like lesions 215 Depends on neurological involvement Investigate according to neurological phenotype 45
Care priorities Seizure treatment and individual organ support Acute seizure management and individual supportive care 27 Individual diabetes and hearing care Individualised glycaemic and audiological management 371819

Can the diagnosis change over time?

Someone diagnosed with MIDD can later develop stroke-like episodes and be described as having features of MELAS too. That is possible, but it is not an inevitable next stage. The diagnosis describes the pattern seen so far; it does not set out a fixed path for your future. People initially diagnosed with MIDD may later develop stroke-like episodes and meet criteria for MELAS or an overlap phenotype. This is not an inevitable or predictable transition. 245

Ongoing follow-up gives you and your team a chance to discuss changes and adapt your care. An individual emergency plan can also help other clinicians know what to do if you become unwell. Surveillance should reflect current manifestations and evolving symptoms. An individual emergency plan supports care during acute illness. 27

warning When to seek urgent help

Neurological changes: some people also develop stroke-like episodes. Seek emergency help for new weakness, speech or vision changes, confusion or seizures. Phenotypic overlap: m.3243A>G can also cause stroke-like episodes. New focal deficits, encephalopathy or seizures require urgent assessment. 27

Why the same mutation can affect people differently

A cell can contain both changed and unchanged copies of mitochondrial DNA. This mixture is called heteroplasmy, and its proportions can differ between organs and between people. Heteroplasmy is the coexistence of variant and reference mtDNA molecules. Variant fractions differ across tissues and individuals. 151011

The proportion of changed mitochondrial DNA is called heteroplasmy. It differs between tissues and can change with age. There is no reliable blood or urine percentage range that defines MIDD or predicts your future health. Heteroplasmy varies by tissue and age. Blood levels of m.3243A>G often decline over time. Neither fixed tissue ranges nor a single measurement reliably define MIDD or predict individual progression. 5610

Your team puts the result together with your symptoms, family history and other tests. If you want to understand your own percentage, the guide to the mutation explains what it can and cannot tell you. Interpret heteroplasmy alongside the sampled tissue, age, phenotype and family history. See the mutation guide for the limits of individual prognostic interpretation. 510

What this means for your care

You do not need to settle every question about the label before discussing the care you need. Start with the symptoms affecting you, the checks your team recommends and anything that has changed since your last appointment. The questions for your doctor can help you prepare. Care and surveillance should be based on current manifestations, baseline findings and evolving symptoms. Use the appointment questions to discuss an individual plan. 7

A low or negative blood result may need further investigation if your history suggests mitochondrial disease. The genetics team may use urine or another sample and a sensitive test. A negative blood result does not exclude low-level m.3243A>G. Sample selection and assay sensitivity should match age, phenotype and clinical suspicion; urine may improve detection. 6 Read more about testing and diagnosis.

Medicine choices also depend on your particular situation, including your genetic diagnosis, kidney and liver function, and what the treatment is for. The medication safety guide explains the questions to discuss with your team. Medication decisions require the specific genotype, indication and organ function to be considered. See the medication safety guide for individual review, including metformin. 78918

The variant can be passed through the mother; the amount inherited and health effects vary. Maternal transmission with variable segregation of heteroplasmic mtDNA and uncertain phenotype prediction. 2021 The family planning guide goes into this in more detail.

References

21 sources

Sources for the information on this page.

  1. El-Hattab AW, Adesina AM, Jones J, Scaglia F. (2015). MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options. Molecular genetics and metabolism. ReviewDOI↑ Back to text
  2. Mancuso M, Bellusci M, Carelli V, de Coo I, Diodato D, Distelmaier F, Hikmat O, Hirano M, Horvath R, Karaa A, Klopstock T, Koenig MK, Kornblum C, La Morgia C, Lopriore P, Martikainen MH, McFarland R, Musumeci O, Pitceathly RDS, Primiano G, Rahman S, Scaglia F, Schaefer A, Schiff M, Semmler L, Lamperti C, Servidei S. (2026). Diagnostic Criteria and Management of MELAS and Stroke-Like Episodes: Consensus-Based Statements. European journal of neurology. Clinical guidanceDOIFull text↑ Back to text
  3. Chanoine JP, Thompson DM, Lehman A. (2025). Diabetes Associated With Maternally Inherited Diabetes and Deafness (MIDD): From Pathogenic Variant to Phenotype. Diabetes. ReviewDOIFull text↑ Back to text
  4. Nesbitt V, Pitceathly RD, Turnbull DM, Taylor RW, Sweeney MG, Mudanohwo EE, Rahman S, Hanna MG, McFarland R. (2013). The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation--implications for diagnosis and management. Journal of neurology, neurosurgery, and psychiatry. Research articleDOI↑ Back to text
  5. Pickett SJ, Grady JP, Ng YS, Gorman GS, Schaefer AM, Wilson IJ, Cordell HJ, Turnbull DM, Taylor RW, McFarland R. (2018). Phenotypic heterogeneity in m.3243A>G mitochondrial disease: The role of nuclear factors. Annals of clinical and translational neurology. Research articleDOIFull text↑ Back to text
  6. Mavraki E, Labrum R, Sergeant K, Alston CL, Woodward C, Smith C, Knowles CVY, Patel Y, Hodsdon P, Baines JP, Blakely EL, Polke J, Taylor RW, Fratter C. (2023). Genetic testing for mitochondrial disease: the United Kingdom best practice guidelines. European journal of human genetics : EJHG. Clinical guidanceDOIFull text↑ Back to text
  7. Sue CM, Balasubramaniam S, Bratkovic D, Bonifant C, Christodoulou J, Coman D, Crawley K, Edema-Hildebrand F, Ellaway C, Ghaoui R, Kava M, Kearns LS, Lee J, Liang C, Mackey DA, Murray S, Needham M, Rius R, Russell J, Smith NJC, Thyagarajan D, Wools C. (2022). Patient care standards for primary mitochondrial disease in Australia: an Australian adaptation of the Mitochondrial Medicine Society recommendations. Internal medicine journal. Clinical guidanceDOIFull text↑ Back to text
  8. De Vries MC, Brown DA, Allen ME, Bindoff L, Gorman GS, Karaa A, Keshavan N, Lamperti C, McFarland R, Ng YS, O'Callaghan M, Pitceathly RDS, Rahman S, Russel FGM, Varhaug KN, Schirris TJJ, Mancuso M. (2020). Safety of drug use in patients with a primary mitochondrial disease: An international Delphi-based consensus. Journal of inherited metabolic disease. Clinical guidanceDOIFull text↑ Back to text
  9. Mancuso M, Papadopoulou MT, Ng YS, Ardissone A, Bellusci M, Bertini E, Di Vito L, Evangelista T, Fons C, Hikmat O, Horvath R, Klopstock T, Kornblum C, Lamperti C, Licchetta L, Molnar MJ, Varhaug KN, O'Callaghan M, Pressler RM, Schiff M, Servidei S, Szabo N, Gorman GS, Cross JH, Rahman S. (2024). Management of seizures in patients with primary mitochondrial diseases: consensus statement from the InterERNs Mitochondrial Working Group. European journal of neurology. Clinical guidanceDOIFull text↑ Back to text
  10. Grady JP, Pickett SJ, Ng YS, Alston CL, Blakely EL, Hardy SA, Feeney CL, Bright AA, Schaefer AM, Gorman GS, McNally RJ, Taylor RW, Turnbull DM, McFarland R. (2018). mtDNA heteroplasmy level and copy number indicate disease burden in m.3243A>G mitochondrial disease. EMBO molecular medicine. Research articleDOIFull text↑ Back to text
  11. Goto Y, Nonaka I, Horai S. (1990). A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. Research articleDOI↑ Back to text
  12. Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, Battista V, Koenigsberger DY, Pascual JM, Shanske S, Sano M, Mao X, Hirano M, Shungu DC, Dimauro S, De Vivo DC. (2011). Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. Research articleDOIFull text↑ Back to text
  13. Sue CM, Lipsett LJ, Crimmins DS, Tsang CS, Boyages SC, Presgrave CM, Gibson WP, Byrne E, Morris JG. (1998). Cochlear origin of hearing loss in MELAS syndrome. Annals of neurology. Observational studyDOI↑ Back to text
  14. Chinnery PF, Elliott C, Green GR, Rees A, Coulthard A, Turnbull DM, Griffiths TD. (2000). The spectrum of hearing loss due to mitochondrial DNA defects. Brain : a journal of neurology. Research articleDOI↑ Back to text
  15. Tang H, Liu J, Cai X, Leng F, Hu J, Zhao Y, Wang Z, Yu L. (2026). Analysis of acute stroke-like lesions in MELAS: Distribution, potential boundaries and spreading pattern. Neuroimage. Reports. Research articleDOIFull text↑ Back to text
  16. Massin P, Virally-Monod M, Vialettes B, Paques M, Gin H, Porokhov B, Caillat-Zucman S, Froguel P, Paquis-Fluckinger V, Gaudric A, Guillausseau PJ. (1999). Prevalence of macular pattern dystrophy in maternally inherited diabetes and deafness. GEDIAM Group. Ophthalmology. Observational studyDOI↑ Back to text
  17. Guéry B, Choukroun G, Noël LH, Clavel P, Rötig A, Lebon S, Rustin P, Bellané-Chantelot C, Mougenot B, Grünfeld JP, Chauveau D. (2003). The spectrum of systemic involvement in adults presenting with renal lesion and mitochondrial tRNA(Leu) gene mutation. Journal of the American Society of Nephrology : JASN. Research articleDOI↑ Back to text
  18. Chaudhry A, Thompson DM, Chanoine JP. (2026). Diabetes management in maternally inherited diabetes and deafness (MIDD): A review and a proposed treatment algorithm. Diabetes, obesity & metabolism. ReviewDOIFull text↑ Back to text
  19. Varga L, Borecka S, Skopkova M, Rambani V, Sklenar M, Cipkova K, Kickova T, Ugorova D, Kabatova Z, Stanik J, Profant M, Gasperikova D. (2026). Screening for Maternally Inherited Diabetes and Deafness in Large Cohorts of Hearing Impaired and Diabetic Patients. Ear and hearing. Research articleDOIFull text↑ Back to text
  20. Smeets HJM, Sallevelt SCEH, Herbert M. (2023). Reproductive options in mitochondrial disease. Handbook of clinical neurology. ReviewDOI↑ Back to text
  21. Castelluccio N, Spath K, Li D, De Coo IFM, Butterworth L, Wells D, Mertes H, Poulton J, Heindryckx B. (2025). Genetic and reproductive strategies to prevent mitochondrial diseases. Human reproduction update. ReviewDOI↑ Back to text

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