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Disease Profile

Sengers syndrome

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

Q87.8

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)

Cardiomyopathy and cataract; Cataract and cardiomyopathy; cardiomyopathic mitochondrial DNA depletion syndrome 10;

Categories

Congenital and Genetic Diseases; Eye diseases; Heart Diseases;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 1369

Definition
Congenital cataract hypertrophic cardiomyopathy mitochrondrial myopathy (CCM) is a mitochondrial disease (see this term) characterized by cataracts, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise.

Epidemiology
Prevalence of CCM is unknown; approximately 40 cases have been reported to date in disparate locations throughout the world.

Clinical description
Clinical features include congenital cataract (total or rapidly progressive), hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise. CCM may present in two forms, a neonatal lethal form or a chronic form. Hypertrophic cardiomyopathy is diagnosed at birth in half of the patients in both forms. Approximately half of the patients die within the first year of life due to cardiac failure. Nystagmus, strabismus, hypotonia, hyporeflexia and delayed motor development are occasional features. Marked lactic acidemia occurs with even limited muscular exertion. Patients who survive neonatal period and infancy, manifest the chronic form with stable cardiomyopathy and myopathy and have a normal intellect. Physical mobility is impaired due to muscular weakness in most patients.

Etiology
In the majority of CCM patients mutations (nonsense, frame-shift, start codon or splice site) in the AGK gene have been identified. The AGK gene encodes the mitochondrial acylglycerol kinase which plays a role in the assembly of adenine nucleotide translocator (ANT), an essential component of the oxidative phosphorylation in mitochondria. Two patients with distinct autosomal recessive SLC25A4 mutations have been reported (one of whom had cardiomyopathy but not cataract). The SLC25A4 gene encodes the heart and muscle specific isoform 1 of the mitochondrial ANT. The etiology remains genetically unsolved in the rest of cases of CCM. The milder affected individuals carried either splice site or start codon mutations.

Diagnostic methods
Diagnostic procedures include serum and urine analysis for lactic acid, radiology and echocardiogram for findings of cardiomyopathy. Muscle biopsy from cardiac and skeletal muscle reveals storage of lipid and glycogen, mitochondrial abnormalities, ANT deficiency and mild decrease of respiratory chain complexes I and IV. Genetic testing may reveal autosomal recessive mutations in AGK and SLC25A4 and it should be considered early in diagnostic workup.

Differential diagnosis
Differential diagnoses include mitochondrial encephalo-cardio-myopathy due to TMEM70 deficiency, isolated ATP synthase deficiency and Barth syndrome (see these terms).

Antenatal diagnosis
Prenatal genetic testing may be possible for families with affected children.

Genetic counseling
The reported mutations are transmitted in an autosomal recessive manner.

Management and treatment
CCM patients require cataract surgery during infancy and medical management of cardiomyopathy with standard therapy. Patients may require palliative care and a wheelchair for locomotion.

Prognosis
Approximately half of the reported patients die in the first year of life due to cardiac failure. The longest surviving patients are in their fifth decade of life.

Visit the Orphanet disease page for more resources.

Symptoms

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
80%-99% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Lactic acidosis
Increased lactate in body
0003128
Myopathy
Muscle tissue disease
0003198
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
30%-79% of people have these symptoms
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
5%-29% of people have these symptoms
Abnormal electroretinogram
0000512
Corneal dystrophy
0001131
Glaucoma
0000501
Thrombocytopenia
Low platelet count
0001873
Percent of people who have these symptoms is not available through HPO
3-Methylglutaconic aciduria
0003535
Autosomal recessive inheritance
0000007
Developmental cataract
Clouding of the lens of the eye at birth
0000519
Easy fatigability
0003388
Exercise intolerance
Decreased ability to exercise
Inability to exercise

[ more ]

0003546
Exercise-induced lactic acidemia
0004901
Fatigue
Tired
Tiredness

[ more ]

0012378
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Increased serum lactate
0002151
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Mitochondrial myopathy
0003737
Motor delay
0001270
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Respiratory insufficiency
Respiratory impairment
0002093
Variable expressivity
0003828

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. 
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
    • PubMed is a searchable database of medical literature and lists journal articles that discuss Sengers syndrome. Click on the link to view a sample search on this topic.