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Disease Profile

Phosphoglycerate kinase deficiency

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

Childhood

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ICD-10

E74.0

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)

PGK deficiency; Phosphoglycerate kinase 1 deficiency; PGK1 deficiency

Categories

Blood Diseases; Congenital and Genetic Diseases; Metabolic disorders;

Summary

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

Orpha Number: 713

Definition
A rare inborn errors of metabolism characterized by variable combinations of non-spherocytic hemolytic anemia, myopathy, and various central nervous system abnormalities.

Epidemiology
Phosphoglycerate kinase (PGK) deficiency prevalence is unknown but about 30 unrelated affected families have been reported so far.

Clinical description
The majority of patients present with chronic hemolytic anemia, which may be severe in some cases. Myopathy is a common finding and is characterized by exercise-intolerance, muscle weakness, cramping, myalgia and episodes of myoglobinuria. Rhabdomyolysis has also been reported in a few patients. Intellectual deficit is frequent, and other central nervous system manifestations may be also present including hemiplegic migraines, epilepsy, ataxia and tremor. Only a few patients show all three cardinal features of the disorder (hemolytic anemia, central nervous system abnormalities and myopathy), and several cases of PGK deficiency with myopathy in the absence of hemolytic anemia have been reported. Only one asymptomatic patient has been described with mild PGK deficiency.

Etiology
PGK deficiency is caused by mutations in the PGK1 gene (Xq13.3) and around 20 different disease-causing variants have been identified so far in affected families. PGK is a key enzyme in the glycolytic pathway catalyzing the conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate and generating ATP. PGK is a ubiquitous enzyme expressed in all tissues except the testes.

Diagnostic methods
Diagnosis is made on the basis of the clinical picture, together with biochemical studies revealing low erythrocyte and muscle PGK enzyme activity (below 23% and 25% of normal respectively), and identification of PGK1 gene mutations by molecular analysis.

Differential diagnosis
The differential diagnosis should include other causes of hereditary non-spherocytic hemolytic anemia.

Antenatal diagnosis
Molecular prenatal diagnosis is feasible for families of an index case.

Genetic counseling
PGK deficiency is inherited as an X-linked trait and most of the reported patients were hemizygous males. However, heterozygous females may have a variable degree of hemolytic anemia. All women born to affected men will be carriers (mild manifesting or not) with no male to male transmission. Female carriers have a 50 % risk of an affected male or female carrier with each pregnancy.

Management and treatment
In patients with severe chronic anemia, regular blood transfusions are required. Splenectomy has been shown to be beneficial in some cases.

Prognosis
The prognosis is variable, depending on the severity of the anemia and on the presence of the other manifestations.

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
30%-79% of people have these symptoms
Ataxia
0001251
Decreased hemoglobin concentration
0020062
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Exercise-induced muscle fatigue
0009020
Exercise-induced myalgia
Exercise-induced muscle pain
Muscle pain on exercise
Muscle pain with exercise
Muscle pain, exercise-induced

[ more ]

0003738
Global developmental delay
0001263
Hemolytic anemia
0001878
Hyperbilirubinemia
High blood bilirubin levels
0002904
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Muscle spasm
0003394
Muscle weakness
Muscular weakness
0001324
Myoglobinuria
0002913
Myopathy
Muscle tissue disease
0003198
Reticulocytosis
Increased immature red blood cells
Increased number of immature red blood cells

[ more ]

0001923
Rhabdomyolysis
Breakdown of skeletal muscle
0003201
Tremor
0001337
5%-29% of people have these symptoms
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Retinal dystrophy
Breakdown of light-sensitive cells in back of eye
0000556
Visual loss
Loss of vision
Vision loss

[ more ]

0000572
1%-4% of people have these symptoms
Blindness
0000618
Percent of people who have these symptoms is not available through HPO
Emotional lability
Emotional instability
0000712
Exercise intolerance
Decreased ability to exercise
Inability to exercise

[ more ]

0003546
Exercise-induced muscle cramps
Exercise-induced muscle cramping
Muscle cramps following exercise
Muscle cramps on exercise
Muscle cramps on exertion
Muscle cramps with exertion

[ more ]

0003710
Exercise-induced myoglobinuria
0008305
Seizure
0001250
X-linked recessive inheritance
0001419

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 Phosphoglycerate kinase deficiency. This website is maintained by the National Library of Medicine.

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.