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Disease Profile

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

G71.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Mitochondrial encephalomyopathy aminoacidopathy; Mitochondrial dna depletion syndrome, encephalomyopathic form with methylmalonic aciduria, autosomal recessive; Booth-Haworth-Dilling syndrome;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases;

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]

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]

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.

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

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]

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]

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 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

    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

      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.

        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/.

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