Deficienza di fosfoglicerato chinasi 1

Synonyms: Phosphoglycerokinase deficiency, PGK deficiency, PGK1 deficiency, Haemolytic anaemia with PGK Deficiency,

Phosphoglycerate kinase deficiency is a hereditary metabolic disease. Phosphoglycerate kinase (PGK1) is a ubiquitous glycolytic enzyme that catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate generating one molecule of ATP. Its gene lies on the X-chromosome (locus Xq13) and there are related pseudogenes on the X-chromosome and chromosome 19.¹

It is a complex enzyme: several subtypes of deficiency have been identified,² based on the tissues in which the enzyme deficiency occurs and the type of inheritance. Clinically, there are two distinct syndromes:

• A pure muscle syndrome characterized by recurrent cramps and muscle breakdown in response to intense exercise.³

• A "muscle plus" syndrome which may feature mental retardation and/or haemolytic anaemia.

Different mutations of the erythrocyte enzyme PGK1 gene have been identified but the reason for the multifarious clinical manifestations of mutations of the same gene remains unknown.⁴

Epidemiologia

• It is extremely rare.

• The gene encoding the erythrocyte enzyme PGK1 is X-linked and PGK is transmitted as an X-linked recessive disorder in nearly 75%. Females are carriers and have a 50% chance of transmitting the gene to an affected son or a carrier daughter. Affected males produce carrier daughters and unaffected sons.

• It is inherited as an autosomal recessive in about 25%.⁵

Presentazione

• Presentation is variable but occurs between infancy and adolescence.

• Clinical findings include:
  

  • Muscle pain and weakness

  • Rust-coloured urine after vigorous exercise due to myoglobinuria

• Other features are rare and highly variable but may include:
  

  • Nausea after exercise

  • Variable degrees of mental retardation

  • Convulsioni

  • Anemia emolitica

• Some patients may have a purely myopathic syndrome with progressive proximal muscle weakness and episodes of myoglobinuria, exercise intolerance and easy fatigue.

• There can be emotional lability, aphasia with impaired ability to comprehend speech or writing and hemiplegia.

• Female carriers may have haemolytic anaemia.

Diagnosi differenziale

There are a number of enzyme defects that can cause myoglobinuria⁶ as well as other causes to remember:

• Biochemical abnormalities (eg ipokaliemia, hypophosphataemia)

• Miopatie

• McArdle's disease (Glycogen storage disorder V) and Tarui's disease (Glycogen storage disorder VII)

• Acetyl-CoA dehydrogenase deficiency and lactate dehydrogenase deficiency

• Polimiosite e dermatomiosite

• Ipertermia maligna

• Sindrome maligna da neurolettici

• Sindrome da schiacciamento

• Muscle ischaemia secondary to arterial occlusion or insufficiency

• Setticemia

• Drug abuse

Indagini

• Diagnostic testing is available for the absence of the enzyme phosphoglycerate kinase.

• There is recurrent myoglobinuria, especially after exercise.

• Serum CK levels are high or normal.

• Anaerobic exercise produces no rise in lactate.

• Gene mutation identification within family groups.

Gestione

Non-Drug

Strenuous exercise should be avoided.

Farmaci

None are of proven value.

Chirurgia

Splenectomy can reduce the haemolytic anaemia and the need for transfusion.⁷

Complicazioni

Myoglobinuria from prolonged exercise can produce renal damage.

Prognosi

Severity varies but the myopathic syndrome is usually slowly progressive. In one study of a large family, many sufferers died before reaching adulthood.⁸

Prevenzione

Identification of the gene⁹ may permit prenatal diagnosis with a view to termination of pregnancy.