What are the other Names for this Condition? (Also known as/Synonyms)

• 2-Ketoglutarate Dehydrogenase Deficiency
• Alpha-KGD Deficiency
• Oxoglutaric Aciduria

What is Alpha-Ketoglutarate Dehydrogenase Deficiency? (Definition/Background Information)

• Alpha-Ketoglutarate Dehydrogenase Deficiency, also known as oxoglutaricaciduria, is a very rare tricarboxylic acid cycle disorder, resulting from a deficiency in alpha-ketoglutarate dehydrogenase (one of the three subunits of the alpha-ketoglutarate dehydrogenase complex)
• The disorder most often presents in the neonatal period with hypotonia, severe encephalopathy, extrapyramidal signs, pyramidal tract dysfunction and seizures and that frequently results in death in early childhood
• Metabolic acidosis, elevated lactate and glutamate levels and variable degrees of glutaric aciduria are noted
• Sudden death, myocardiopathy, and hepatic disorders have also been reported in some cases

(Source: Oxoglutaricaciduria; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Alpha-Ketoglutarate Dehydrogenase Deficiency? (Age and Sex Distribution)

• Alpha-Ketoglutarate Dehydrogenase Deficiency is a rare congenital disorder. The presentation of symptoms occur after birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Alpha-Ketoglutarate Dehydrogenase Deficiency? (Predisposing Factors)

• Currently, no risk factors have been clearly identified for Alpha-2 Deficient Collagen Disease

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Alpha-Ketoglutarate Dehydrogenase Deficiency? (Etiology)

The cause of development of Alpha-Ketoglutarate Dehydrogenase Deficiency is unknown.

What are the Signs and Symptoms of Alpha-Ketoglutarate Dehydrogenase Deficiency?

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of Alpha-Ketoglutarate Dehydrogenase Deficiency cases:

• Abnormal urine alpha-ketoglutarate concentration
• Ataxia
• Hypertonia
• Skeletal muscle atrophy

Frequently present symptoms in 30-79% of Alpha-Ketoglutarate Dehydrogenase Deficiency cases:

• Alpha-KGD Deficiency
• Abnormality of movement
• Abnormality of the salivary glands
• Hydrocephalus

Other signs and symptoms of Alpha-Ketoglutarate Dehydrogenase Deficiency may include:

• Congenital lactic acidosis
• Increased serum lactate
• Metabolic acidosis
• Muscular hypotonia

(Source: Alpha-Ketoglutarate Dehydrogenase Deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is Alpha-Ketoglutarate Dehydrogenase Deficiency Diagnosed?

Alpha-Ketoglutarate Dehydrogenase Deficiency is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Alpha-Ketoglutarate Dehydrogenase Deficiency?

The complications of Alpha-Ketoglutarate Dehydrogenase Deficiency may include:

• Seizures
• Dysfunction of the heart and liver
• Severe neurological damage
• Death in childhood

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Alpha-Ketoglutarate Dehydrogenase Deficiency Treated?

There is no cure for Alpha-Ketoglutarate Dehydrogenase Deficiency. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Alpha-Ketoglutarate Dehydrogenase Deficiency be Prevented?

• Currently, Alpha-Ketoglutarate Dehydrogenase Deficiency is not preventable, since the cause of the disorder is unknown
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Alpha-Ketoglutarate Dehydrogenase Deficiency? (Outcomes/Resolutions)

• The prognosis of Alpha-Ketoglutarate Dehydrogenase Deficiency is dependent upon the severity of the signs and symptoms and associated complications, if any
• The symptoms of the disorder are most often severe and Alpha-KGD Deficiency is known to be typically fatal during early childhood. In some cases, sudden deaths are also reported

Additional and Relevant Useful Information for Alpha-Ketoglutarate Dehydrogenase Deficiency:

Alpha-Ketoglutarate Dehydrogenase Deficiency is also known by the following names: 

• 2 Alpha Ketoglutarate Dehydrogenase Deficiency
• Oxoglutaricaciduria

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/