Sengers syndrome

Title

Other Names:

Cardiomyopathy and cataract; Cataract and cardiomyopathy; cardiomyopathic mitochondrial DNA depletion syndrome 10; Cardiomyopathy and cataract; Cataract and cardiomyopathy; cardiomyopathic mitochondrial DNA depletion syndrome 10; Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome See More

Categories:

Congenital and Genetic Diseases; Eye diseases; Heart Diseases; Congenital and Genetic Diseases; Eye diseases; Heart Diseases; Metabolic disorders See More

Summary Summary

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

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.

Last updated: 6/1/2014

Symptoms 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.

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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

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2020

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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 Genetics Home Reference.

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 Supporting this Disease

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

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.

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