Rare Endocrinology News

Disease Profile

Glutaric acidemia type II

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.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

All ages

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ICD-10

E71.3

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)

Glutaric acidemia type 2; Glutaric acidemia 2; Glutaric aciduria 2;

Categories

Congenital and Genetic Diseases; Heart Diseases; Metabolic disorders;

Summary

Glutaric acidemia type II (GA2) is a disorder that interferes with the body's ability to break down proteins and fats to produce energy. The severity of GA2 varies widely among affected individuals. Some have a very severe form which appears in the neonatal period and may be fatal; individuals with this form may be born with physical abnormalities including brain malformations, an enlarged liver, kidney malformations, unusual facial features, and genital abnormalities. They may also emit an odor resembling sweaty feet. Others have a less severe form which may appear in infancy, childhood, or even adulthood. Most often, GA2 first appears in infancy or early childhood as a sudden episode of a metabolic crisis that can cause weakness, behavior changes (such as poor feeding and decreased activity) and vomiting.[1] GA2 is inherited in an autosomal recessive manner and is caused by mutations in the ETFA, ETFB, or ETFDH genes.[1] Treatment varies depending on the severity and symptoms but often includes a low fat, low protein, and high carbohydrate diet.[2]

Symptoms

Signs and symptoms of glutaric acidemia type II (GA2) can vary widely depending on the age of onset and severity of the condition in each affected individual. In most cases, the condition appears in infancy or early childhood as a sudden episode called a metabolic crisis which causes weakness; behavior changes such as poor feeding and decreased activity; and vomiting. These crises can be life-threatening and may be triggered by common childhood illnesses or other stresses on the body.

The most severe cases may appear in the neonatal period (within the first 4 weeks of life) and may also be characterized by the presence of physical abnormalities at birth. These abnormalities may include brain malformations; an enlarged liver (hepatomegaly); a weakened and enlarged heart (dilated cardiomyopathy); fluid-filled cysts and other malformations of the kidneys; unusual facial features; and genital abnormalities. Some affected individuals have a characteristic odor resembling sweaty feet.

Other cases are less severe and may appear later in childhood, in adolescence, or in adulthood. In the most mild cases, muscle weakness may be the first sign of the disorder.[3]

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
30%-79% of people have these symptoms
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

0003236
Exercise-induced muscle fatigue
0009020
Hypoglycemia
Low blood sugar
0001943
Muscular hypotonia
Low or weak muscle tone
0001252
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
5%-29% of people have these symptoms
3-Methylglutaric aciduria
0003344
Abnormality of the pinna
Abnormally shaped ears
Auricular malformation
Deformed ears
Malformed ears

[ more ]

0000377
Areflexia
Absent tendon reflexes
0001284
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

0001635
Decreased liver function
Liver dysfunction
0001410
Decreased plasma carnitine
0003234
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Difficulty climbing stairs
Difficulty walking up stairs
0003551
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Dyspnea
Trouble breathing
0002094
Elevated hepatic transaminase
High liver enzymes
0002910
Elevated plasma acylcarnitine levels
0045045
Ethylmalonic aciduria
0003219
Exercise intolerance
Decreased ability to exercise
Inability to exercise

[ more ]

0003546
Fatigable weakness of neck muscles
0030199
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Glutaric aciduria
0003150
Hepatic periportal necrosis
0002614
Hepatomegaly
Enlarged liver
0002240
High forehead
0000348
Hyperammonemia
High blood ammonia levels
0001987
Hyperlordosis
Prominent swayback
0003307
Increased intramyocellular lipid droplets
0012240
Increased lactate dehydrogenase level
0025435
Lactic acidosis
Increased lactate in body
0003128
Lacticaciduria
High urine lactic acid levels
0003648
Metabolic acidosis
0001942
Respiratory failure
0002878
Seizure
0001250
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Telecanthus
Corners of eye widely separated
0000506
Vomiting
Throwing up
0002013
Wide anterior fontanel
Wider-than-typical soft spot of skull
0000260
1%-4% of people have these symptoms
Abnormality of the genital system
Genital abnormalities
Genital abnormality
Genital anomalies
Genital defects

[ more ]

0000078
Acute pancreatitis
Acute pancreatic inflammation
0001735
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Cardiomyopathy
Disease of the heart muscle
0001638
Cardiorespiratory arrest
0006543
Encephalopathy
0001298
Gliosis
0002171
Gray matter heterotopia
0002282
Inability to walk
0002540
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Polycystic kidney dysplasia
0000113
Poor head control
0002421
Restrictive ventilatory defect
Stiff lung or chest wall causing decreased lung volume
0002091
Reye syndrome-like episodes
0006582
Rhabdomyolysis
Breakdown of skeletal muscle
0003201
Scapular winging
Winged shoulder blade
0003691
Percent of people who have these symptoms is not available through HPO
Abnormal facial shape
Unusual facial appearance
0001999
Acidosis
0001941
Autosomal recessive inheritance

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
  • The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.
  • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

    Treatment

    The goal of treatment is to prevent long-term problems. However, children who have repeated metabolic crises may develop life-long learning problems. Individuals with glutaric acidemia type II should consult with a metabolic doctor and a dietician who can help to develop an appropriate dietary plan. Some treatments may be recommended for some children but not for others. When necessary, treatment should be continued throughout the lifetime. The following treatments are often recommended:[4][5]

    • Avoidance of fasting. Infants and young children with glutaric acidemia type II should eat frequent meals in order to prevent hypoglycemia and metabolic crises.
    • A low-fat, lowprotein, high-carbohydrate diet may be advised.
    • Riboflavin, L-carnitine and glycine supplements may be needed. These supplements help the body create energy.
    • Alert the child's doctor if they should become ill, as illness can trigger a metabolic crisis.

    Management Guidelines

    • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

      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

        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.

          Where to Start

          • Genetics Home Reference (GHR) contains information on Glutaric acidemia type II. This website is maintained by the National Library of Medicine.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
          • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

            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 Glutaric acidemia type II. Click on the link to view a sample search on this topic.

              References

              1. Glutaric acidemia type II. Genetics Home Reference (GHR). July 2008; https://www.ghr.nlm.nih.gov/condition/glutaric-acidemia-type-ii. Accessed 11/14/2011.
              2. Glutaricaciduria II. NORD. May 10, 2008; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/378/viewAbstract. Accessed 8/16/2013.
              3. Glutaric acidemia type II. Genetics Home Reference. July 2008; https://www.ghr.nlm.nih.gov/condition/glutaric-acidemia-type-ii. Accessed 8/16/2013.
              4. Glutaric acidemia, type 2. STAR-G Genetic Fact Sheets For Parents. August 16 2013; https://www.newbornscreening.info/Parents/fattyaciddisorders/GA2.html.
              5. Olpin S. Multiple acyl-CoA dehydrogenation deficiency (MADD). Orphanet. February 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=26791.

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