Phosphofructokinase Deficiency Glycogen Storage Disease

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Synonyms: Tarui's disease, glycogen storage disease type VII, muscle phosphofructokinase deficiency

Phosphofructokinase (PFK) deficiency is a glycogen storage disorder. It is rare and is inherited as an autosomal recessive disorder. There is a mutation in the gene encoding muscle PFK on chromosome 12.[1] There is also reduced activity of red cell PFK.[2] The main clinical features include exercise intolerance, muscle cramping, exertional myopathy, compensated haemolysis and myoglobinuria.[1] There are three subtypes:[2]

  • Infantile-onset (a few rare cases have been reported).
  • Classic (most common).
  • Late-onset.

Phosphofructokinase (PFK) is needed for glycolysis. The enzyme deficiency results in the accumulation of glycogen in the tissues. The enzyme deficiency can also lead to increased uric acid production and therefore possible gout. There may be a compensated haemolytic anaemia.

PFK has muscle, liver and platelet subunits. In muscle tissue, it is only composed of muscle subunits but erythrocyte PFK is composed of both muscle and liver subunits. This means that in classic PFK deficiency, there is no PFK activity in muscle and about 50% activity in erythrocytes.

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  • It is very rare and has been reported in approximately 100 patients worldwide.[3]
  • Symptoms may be mild in some people so there may be some cases that go unrecognised.[2]
  • Males appear to be affected more commonly than females.[2]
  • It is more common in Ashkenazi Jews.[1][4]
  • Infantile-onset form:
    • The cases reported have presented under the age of 1 year.
    • Clinical features can include myopathy, psychomotor retardation, cataracts and joint contractures.
    • Death has occurred during childhood in all but one of the reported cases.[6][7] There is a 2007 case report of a boy with phosphofructokinase (PFK) deficiency who presented, aged 3 days, with neonatal seizures and early infantile nonprogressive muscle weakness. He was gaining in his developmental milestones and his seizures were controlled on medication.[8]
  • Classic form:
  • Late-onset form:
    • This presents in adults as progressive muscle and limb weakness without cramps or myoglobinuria.[11]
  • Blood tests:
  • Urinalysis:
    • There may be myoglobinuria after exercise.
  • Imaging and electrophysiology:
    • Cortical atrophy and ventricular dilatation may be seen on brain imaging in the infantile form.
    • Electromyography (EMG) may show changes consistent with myopathy or may be normal.[2][5]
  • Ischaemic forearm test:[2]
    • Inflate a blood pressure cuff around the arm to above systolic pressure.
    • Ask the patient to grasp an object in the hand of their same arm at a rate of 1-2 times per second for 2-3 minutes.
    • Take blood for creatine kinase, ammonia, and lactate as well as urinalysis for myoglobin 5, 10 and 20 minutes after inflating the cuff. (Also carry out these tests as a baseline just before the cuff is inflated.)
    • If lactate levels do not rise with ammonia levels, this is a positive test and is evidence of either Tarui's disease, Cori's disease (glycogen storage disease type III) or McArdle's disease (glycogen storage disease type V).
  • Muscle biopsy:
    • Assay of phosphofructokinase (PFK) in muscle tissue shows reduced levels and can give a definitive diagnosis.[2]
  • No specific treatment exists.
  • The patient (or parents/carers) should be given information about the disorder and advised to avoid high-carbohydrate meals, as they can exacerbate exercise intolerance.[2]
  • There is evidence that a high-protein diet may improve muscle function and slow progression of the disease.[5]
  • Vigorous exercise should be avoided, as it causes myoglobinuria.[2]
  • Renal function should be monitored.
  • Genetic counselling should be offered. Prenatal detection may be possible in families with identifiable mutations.[2]
  • Gene therapy may be possible for the future.
  • Myoglobinuria and, rarely, renal failure.
  • Haemolysis and jaundice.
  • Gallstones.
  • Gout.
  • Heart muscle involvement.[9]
  • The few reported cases with the infantile variant have died during early childhood (with the exception of the recent case report which may be a different variant).[2]
  • Other types should be relatively mild disorders, only requiring minor lifestyle restrictions to avoid complications such as renal failure.[2]

Further reading & references

  1. Glycogen storage disease VII, Online Mendelian Inheritance in Man (OMIM)
  2. Ierardi-Curto L; Genetics of Glycogen-Storage Disease Type VII, Medscape, Feb 2009
  3. Toscano A, Musumeci O; Tarui disease and distal glycogenoses: clinical and genetic update. Acta Myol. 2007 Oct;26(2):105-7.
  4. Raben N, Sherman JB, Adams E, et al; Various classes of mutations in patients with phosphofructokinase deficiency (Tarui's disease). Muscle Nerve. 1995;3:S35-8.
  5. Anderson WE, Glycogen storage disease type VII, Medscape, Jan 2010
  6. Danon MJ, Carpenter S, Manaligod JR, et al; Fatal infantile glycogen storage disease: deficiency of phosphofructokinase and phosphorylase b kinase. Neurology. 1981 Oct;31(10):1303-7.
  7. Amit R, Bashan N, Abarbanel JM, et al; Fatal familial infantile glycogen storage disease: multisystem phosphofructokinase deficiency. Muscle Nerve. 1992 Apr;15(4):455-8.
  8. Al-Hassnan ZN, Al Budhaim M, Al-Owain M, et al; Muscle phosphofructokinase deficiency with neonatal seizures and nonprogressive course. J Child Neurol. 2007 Jan;22(1):106-8.
  9. Finsterer J, Stollberger C, Kopsa W; Neurologic and cardiac progression of glycogenosis type VII over an eight-year period. South Med J. 2002 Dec;95(12):1436-40.
  10. Finsterer J, Stollberger C; Progressive mitral valve thickening and progressive muscle cramps as manifestations of glycogenosis VII (Tarui's Disease). Cardiology. 2008;110(4):238-40. Epub 2007 Dec 12.
  11. Danon MJ, Servidei S, DiMauro S, et al; Late-onset muscle phosphofructokinase deficiency. Neurology. 1988 Jun;38(6):956-60.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Michelle Wright
Current Version:
Peer Reviewer:
Prof Cathy Jackson
Last Checked:
Document ID:
2607 (v23)