LPIN1 Deficiency

Contact our caring team on 0800 652 3181 for help and support. Our phone lines open 10am-4pm, Monday to Friday.

Calls are free from UK landlines and mobiles. Calls from business lines may be charged – please check with your provider.

Prefer to email? Our email address is contact@metabolicsupport.org.

This disorder is caused by a fault in the LPIN1 gene which leads to problems breaking down and using (metabolising) fatty acids. This causes stress to the skeletal muscle resulting in a condition called rhabdomyolysis.

Since first being reported in 2008, this disorder has gained increasing awareness and diagnoses. As of 2022, 71 cases of LPIN1 deficiency have been reported in the literature.

The most prominent symptoms are rhabdomyolysis and exercise intolerance (fatigue).

Rhabdomyolysis is a serious condition in which muscle tissue rapidly breaks down and releases muscle fibres and components into the bloodstream. This can cause severe health problems including a high level of potassium in the blood (hyperkalaemia). Creatine kinase is an enzyme found in muscle fibres, high levels of this in the blood suggest muscle damage and as such is a key finding in rhabdomyolysis.

Myoglobinuria is often an early sign of rhabdomyolysis occurring and often happens prior to a rise in creatine kinase levels. Myoglobinuria may resolve or improve despite other effects of rhabdomyolysis continuing. Myoglobin is a protein found in skeletal muscle and when it enters the bloodstream it can cause significant damage to the kidneys. When myoglobinuria occurs the urine often turns a dark brown colour along with a positive test for the presence of blood.

As well as the clinical findings, rhabdomyolysis causes muscle aches and pain (myalgia) and muscle weakness. Swelling of isolated muscles has also been recorded. Rhabdomyolysis and exercise intolerance occur in episodes which are most commonly triggered by the following:
• Feverish illnesses
• Infections
• Intense exercise
• Long periods without food (fasting)
• Anaesthesia

Certain drugs (theophylline, mefenamic acid, co-trimoxazole, and combined oral contraceptive pills) have also been connected with precipitating episodes.

From case studies in the literature, episodes can be mild or severe. Severe episodes may last for weeks and can cause some or all of the following:
• Muscle aches, pains, and/or swelling
• Weakness in all limbs
• Blue skin and lips (cyanosis) – a result of low oxygen levels in the blood
• Increased respiratory rate and heart rate
• Impaired muscle movement
• Weak muscle tone (hypotonia)
• Reduced reflexes
• Breathing difficulties
• Severe irregular heartbeat (arrhythmia)
• Impaired kidney function

This condition almost always presents in children under the age of 5/6. Rarely it may present in adolescence or adulthood. With age, the frequency and intensity of the attacks reduce. Episodes during childhood can be life-threatening in their severity and in approximately a third of cases the first episode is fatal.

Tests used to diagnose LPIN1 deficiency may include a clinical evaluation, specialised blood and urine tests, heart function tests and monitoring. Rhabdomyolysis is suggestive of a number of different conditions and so diagnosis may be a process of elimination and so awareness is vital. LPIN1 deficiency should be considered for any cases of a genetic or metabolic condition which features rhabdomyolysis. Genetic testing is used to confirm the diagnosis.

There is no cure for LPIN1 deficiency. Treatment is focused on the management of episodes and the avoidance of triggers. An emergency management plan should be implemented with clear instructions on what to do to identify and manage episodes early. In the event of an acute episode the trigger should be removed or treated (in the case of infection). Intensive treatment and haemofiltration may be required to treat severe kidney impairment.

LPIN1 deficiency can severely affect heart functions and certain medications (i.e. oral bronchodilators) which might be considered for use in the management of episodes can contribute to irregular heart rhythms during severe episodes. Therefore those diagnosed with this condition should receive regular heart monitoring and healthcare professionals being aware of safe management strategies for episodes.

Some reports suggest that during exercise, illness, or other situations which increase the risk of an episode occurring, a higher intake of calories, and carbohydrates may reduce the risk. Others report suggest a low fat diet with medium chain triglycerides (MCT) and L-carnitine may be beneficial.

During childhood the intensity of episodes can cause severe cardiac (heart) problems and multi-organ failure, and can be fatal within hours.

A person develops LPIN1 deficiency if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has one copy of the faulty gene is known as a carrier.
If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.

A genetic counsellor can tell you more about the inheritance pattern and help to explain it. They can also advise on genetic testing for the rest of your family and provide any guidance on future family planning.

Milly-Rose sadly passed away in 2023, we are grateful that her parents have decided to share their experiences of LPIN1 and their daughter’s story. You can read Milly-Rose’s story here: Milly’s Story: LPIN1 Deficiency (Exon 18 co-deletion) – Metabolic Support UK

https://pmc.ncbi.nlm.nih.gov/articles/PMC7275236/
https://www.sciencedirect.com/science/article/abs/pii/S0960896622001961
https://discovery.ucl.ac.uk/id/eprint/10102612/1/Pizzamiglio%20et%20al%2C%202020.pdf
https://patient.info/doctor/rhabdomyolysis-and-other-causes-of-myoglobinuria

This information about metabolic diseases is provided by Metabolic Support UK and is intended for educational purposes only. It should not be used for diagnostic or treatment purposes.

Should you require more detailed information please contact Metabolic Support UK by email (contact@metabolicsupport.org) or by telephone ( 0800 652 3181). For specific medical information regarding a disorder or individual please contact your GP or Paediatrician. Metabolic Support UK accepts no responsibility for any errors or omissions nor does Metabolic Support UK assume any liability of any kind for the content of any information contained within this summary or any use that you may make of it.