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  3. Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria
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Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria


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Other Names:
Mitochondrial encephalomyopathy aminoacidopathy; Mitochondrial dna depletion syndrome, encephalomyopathic form with methylmalonic aciduria, autosomal recessive; Booth-Haworth-Dilling syndrome; Mitochondrial encephalomyopathy aminoacidopathy; Mitochondrial dna depletion syndrome, encephalomyopathic form with methylmalonic aciduria, autosomal recessive; Booth-Haworth-Dilling syndrome; mtDNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria; SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria; Mitochondrial DNA depletion syndrome 9 See More
Categories:
Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases; Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases; RDCRN See More
This disease is grouped under:
Mitochondrial DNA depletion syndrome

Summary Summary


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Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (MTDPS9) affects the brain, nervous system, and muscles. Symptoms are different from person to person. They may include muscle weakness, hearing loss, and difficulty feeding and breathing. Other symptoms may include severe low muscle tone, developmental delay, and cognitive impairment. Symptoms usually begin in early infancy and get worse over time, often leading to death in infancy. MTDPS9 is caused by genetic variants in the SUCLG1 gene (also known as the SUCLA1 gene) and is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, clinical exam, imaging studies, and the removal of a small piece of muscle for examination (muscle biopsy). The diagnosis may also be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms and providing support.[1][2]
Last updated: 11/30/2020

Symptoms Symptoms


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The following list includes the most common signs and symptoms in people with mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria. These features may be different from person to person. Some people may have more symptoms than others, and they can range from mild to severe. This list does not include every symptom that has been described in the condition.

Symptoms of mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria may include:[1][2]
  • Muscle weakness
  • Difficulty feeding
  • Inability to sit or hold the head up
  • Hearing loss
  • Poor growth (failure to thrive)
  • Difficulty breathing due to muscle weakness
  • Developmental delay
  • Cognitive impairment
Other symptoms include high levels of lactic acid in the blood and low blood sugar. Symptoms typically begin in early infancy and get worse over time, leading to early death.  Other less common symptoms include stiff joints, an enlarged heart, and eye abnormalities. Not many people with this condition have been reported in the medical literature.[1][2]
Last updated: 11/30/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 41 |
Medical Terms Other Names
Learn More:
HPO ID
1%-4% of people have these symptoms
Areflexia
Absent tendon reflexes
0001284
Death in childhood 0003819
Death in infancy
Infantile death
Lethal in infancy
[ more ]
0001522
Elevated lactate:pyruvate ratio 0032653
Elevated serum alanine aminotransferase 0031964
Elevated serum aspartate aminotransferase 0031956
Feeding difficulties
Feeding problems
Poor feeding
[ more ]
0011968
Focal T2 hyperintense basal ganglia lesion 0007183
Generalized neonatal hypotonia
Generalized low muscle tone in neonate
0008935
Hearing impairment
Deafness
Hearing defect
[ more ]
0000365
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased
[ more ]
0000975
Hypoglycemia
Low blood sugar
0001943
Hypothermia
Abnormally low body temperature
0002045
Increased CSF lactate 0002490
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Infantile onset
Onset in first year of life
Onset in infancy
[ more ]
0003593
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation
[ more ]
0010864
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ]
0001511
Lactic acidosis
Increased lactate in body
0003128
Lacticaciduria
High urine lactic acid levels
0003648
Methylmalonic aciduria 0012120
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Neonatal death
Neonatal lethal
0003811
Neonatal onset 0003623
Persistent head lag 0032988
Poor head control 0002421
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Cerebral atrophy
Degeneration of cerebrum
0002059
Decreased activity of mitochondrial complex I 0011923
Decreased activity of mitochondrial complex III 0011924
Decreased activity of mitochondrial complex IV 0008347
Depletion of mitochondrial DNA in muscle tissue 0009141
Elevated brain lactate level by MRS 0012707
Encephalopathy 0001298
Failure to thrive
Faltering weight
Weight faltering
[ more ]
0001508
Global developmental delay 0001263
Hyperglycinemia
Elevated blood glycine levels
0002154
Hypertaurinemia 0500181
Neonatal respiratory distress
Infantile respiratory distress
Newborn respiratory distress
Respiratory distress, neonatal
[ more ]
0002643
Respiratory failure 0002878
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ]
0003202
Showing of 41 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 1/1/2021

Cause Cause


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Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria occurs when the SUCLG1 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1][2]
Last updated: 11/30/2020

Inheritance Inheritance


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Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria is inherited in an autosomal recessive pattern.[2] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must have a pathogenic variant to cause the condition.
 
People with autosomal recessive conditions inherit one variant from each of their parents. The parents, who each have one gene variant, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Last updated: 11/30/2020

Diagnosis Diagnosis


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Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria is diagnosed based on the symptoms, clinical exam, imaging studies, and the removal of a piece of muscle for examination (muscle biopsy). In addition, blood and urine testing to look for high levels of lactic acid and methylmalonic acid may be helpful. The diagnosis may be confirmed by the results of genetic testing.[1][2]
Last updated: 11/30/2020

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment


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Treatment for mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria is focused on managing the symptoms, and providing enough nutrition and support.[2]

Specialists involved in the care of someone with mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria may include:
  • Neurologist
  • Gastroenterologist
  • Orthopedist
  • Physical therapist
  • Medical geneticist
  • Ear, nose, and throat physician
  • Cardiologist
  • Ophthmologist
  • Audiologist
  • Dietician
Last updated: 11/30/2020

Statistics Statistics


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It is unclear how many people have mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria. There have been about 30 cases of this condition described in the medical literature.[2] 
Last updated: 11/30/2020
Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist


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If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research


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Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • The North American Mitochondrial Disease Consortium (NAMDC) is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria:
    Mitochondrial Disease Community Registry
     

Organizations Organizations


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Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

  • MitoAction
    PO Box 51474
    Boston, MA 02205
    Toll-free: 1-888-648-6228
    Telephone: 1-888-MITO-411 (648-6411) for support line
    E-mail: info@mitoaction.org
    Website: https://www.mitoaction.org/
  • United Mitochondrial Disease Foundation
    8085 Saltsburg Road, Suite 201
    Pittsburgh, PA 15239
    Toll-free: 1-888-317-8633
    Telephone: +1-412-793-8077
    Fax: +1-412-793-6477
    E-mail: info@umdf.org
    Website: https://www.umdf.org
Do you know of an organization? We want to hear from you.

Learn More Learn More


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These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers


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Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References


  1. Basel D. Mitochondrial DNA Depletion Syndromes. Clin Perinatol. Mar 2020; 47(1):123-141. https://pubmed.ncbi.nlm.nih.gov/32000920/.
  2. El-Hattab AW, Saglia F.. SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria. GeneReviews. Mar 30, 2017; https://pubmed.ncbi.nlm.nih.gov/28358460/.
Do you know of a review article? We want to hear from you.
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You can help advance rare disease research!
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