Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Title

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

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

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.

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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: 2/1/2021

Cause Cause

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

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

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

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

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

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Find a Specialist Find a Specialist

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 MedlinePlus Genetics.

Research Research

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

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 Providing General Support

MitoAction
PO Box 310
Novi, MI 48376
Toll-free: 888-648-6228
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

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Learn More Learn More

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

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

Basel D. Mitochondrial DNA Depletion Syndromes. Clin Perinatol. Mar 2020; 47(1):123-141. https://pubmed.ncbi.nlm.nih.gov/32000920/.
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/.

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