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

• Phosphoenolpyruvate Carboxykinase Deficiency Disorder
• Phosphoenolpyruvate Carboxylase Deficiency Disorder
• Phosphopyruvate Carboxylase Deficiency Disorder

What is PEPCK 1 Deficiency Disorder? (Definition/Background Information)

• PEPCK1 Deficiency Disorder is a rare inborn error of metabolism disorder, characterized by the deficiency of the enzyme PEPCK1, one of the enzymes needed for gluconeogenesis, the process by which organisms produce sugars (namely glucose) from non-carbohydrate precursors (such as amino acids)
• The symptoms described in the few cases reported in the medical literature suggest that there may be variation in the severity of the symptoms ranging from severe early-onset cases, to milder late-onset presentations
• In severe cases symptoms may include persistent and very low levels of blood's sugar in newborns (neonatal hypoglycemia), failure to thrive, build-up of lactic acid in the blood (lactic acidosis), liver enlargement (hepatomegaly) and liver failure leading to neurological degeneration
• Milder cases present during childhood with fewer and less serious liver problems. Infections and fasting may trigger the symptoms
• PEPCK1 Deficiency Disorder inheritance is autosomal recessive. It is caused by mutations in the PEPCK1 gene. Some researchers believe that the severity of the disease depend upon the mutations resulting in less or more PEPCK1 activity (the more active the enzyme is, the less severe the disease is, and vice versa)
• The treatment of PEPCK1 Deficiency Disorder depend on the symptoms and may include giving extra carbohydrates during heavy exercise and illness or other times of fasting (formal sick day regimen) by the dietitian
• PEPCK1 Deficiency Disorder is the cytosolic form of the phosphoenolpyruvate carboxykinase (PEPCK) enzyme, the other being the mitochondrial (PEPCK2)

(Source: PEPCK 1 Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets PEPCK 1 Deficiency Disorder? (Age and Sex Distribution)

• PEPCK 1 Deficiency Disorder is a rare congenital disorder, affecting about one in a million individuals
• The presentation of symptoms may occur at birth or in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for PEPCK 1 Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since PEPCK 1 Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for this deficiency disorder

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 PEPCK 1 Deficiency Disorder? (Etiology)

PEPCK 1 Deficiency Disorder is caused by mutation(s) in the PEPCK1 gene.

• This gene codes for the phosphoenolpyruvate carboxykinase-1 enzyme, which catalyzes an important step in the formation of glucose from non-carbohydrate precursors (known as gluconeogenesis)
• The inheritance may be autosomal recessive or mitochondrial

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

If the causative gene for a disease or condition is located on the mitochondrion, then the inheritance is known as mitochondrial.

• Mitochondria are double-membrane cellular organelles present in numerous quantities inside cells
• These organelles are the sites of cellular respiration and energy generation, and are known as the “powerhouses” of cells
• Mitochondria carry their own DNA. Since the egg contributes the cellular environment for fertilization and subsequent embryonic development, the mitochondria are inherited exclusively from the mother (to the offspring)

What are the Signs and Symptoms of PEPCK 1 Deficiency Disorder?

The signs and symptoms of PEPCK 1 Deficiency Disorder may include:

• Apnea
• Cerebral atrophy
• Cyanosis
• EEG abnormality
• Global developmental delay
• Hepatic failure
• Hepatic steatosis
• Hypoglycemia
• Impaired gluconeogenesis
• Infantile onset
• Optic atrophy
• Renal steatosis
• Seizures

(Source: PEPCK 1 Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is PEPCK 1 Deficiency Disorder Diagnosed?

PEPCK 1 Deficiency Disorder 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
• Molecular genetic testing to check for or confirm PEPCK1 gene mutation(s)

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 PEPCK 1 Deficiency Disorder?

The complications of PEPCK 1 Deficiency Disorder may include:

• Sudden falls due to hypoglycemia
• Loss of consciousness
• Ascites
• Gastrointestinal bleeding

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

How is PEPCK 1 Deficiency Disorder Treated?

There is no cure for PEPCK 1 Deficiency Disorder, since it is a genetic condition.

• The treatment is usually given to manage the signs and symptoms and any complication that develops
• Treatment methods may include intake of extra carbohydrates during heavy exercise and illness or other times of fasting, to avoid hypoglycemia

How can PEPCK 1 Deficiency Disorder be Prevented?

Currently, PEPCK 1 Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of PEPCK 1 Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of PEPCK 1 Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for PEPCK 1 Deficiency Disorder:

PEPCK 1 Deficiency Disorder is also known by the following names:

• PEP Carboxykinase Deficiency Disorder
• Phosphoenolpyruvate Carboxykinase-1 (PCK1) Deficiency Disorder

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

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