Diagnosis, Treatment and Prevention of AFLP

DIAGNOSIS

AFLP can be diagnosed through these methods:

• Perform liver biopsy (viewing liver tissue under a microscope) - not advisable due to increased chance of bleeding in AFLP mothers.

- 3 main types of liver biopsy : Percutaneous (most common), Transvenous and Laparoscopic

Percutaneous liver biopsy
[http://digestive.niddk.nih.gov/ddiseases/pubs/liverbiopsy/images/BiopsyNeedle.jpg]

• Ultrasound / Computed Tomography(CT) scan - to detect accumulation of fats around liver

Ultrasound
[http://www.physics.utoronto.ca/~jharlow/teaching/phy138_0708/lec04/ultrasoundx_files/image001.jpg]

• Blood test -a disorder in fatty acid metabolism will lead to: high white blood cell count, increased amount of liver enzymes, low blood sugar and more

Blood test
[http://blogs.prideangel.com/image.axd?picture=blood+test.jpg]

You also can look out for signs and symptoms of AFLP as mentioned in the previous posts, for early treatment and preparations.

TREATMENT and PREVENTION

Due to complications of coagulation and high changes of bleeding that may occur in some AFLP patients, patients are advise to change their coagulation factors before their cesarean delivery.

Close monitoring of mother and fetus is important before the delivery to prevent other complications that may occur during delivery. For patients of AFLP with severe hypoglycemia, they are advise to take intravenous fluid such as Dextrose solution for regulation of their blood glucose levels. If severe hypoglycemia is not manage properly, it may lead to coma or even death.

To prevent mother and baby from further sufferings and complications, once the mother is diagnosed with AFLP, it is best to deliver the baby as soon as possible. The earlier the baby is born, the lesser the risk poses for both the mother and the baby. The condition of the mother should also improve after the delivery if nothing went wrong with the delivery.

Patients of AFLP should be aware of symptoms of AFLP, so that when signs and symptoms of AFLP surface, they should immediately consult the doctor for early treatment. Should AFLP be diagnosed earlier, latter serious complications maybe minimise.

When the case is serious, a liver transplantation may be required.

References:

Sarah A. 2007. Acute Fatty Liver of Pregnancy (AFLP): What You Need to Know. [ONLINE] Available at:http://voices.yahoo.com/acute-fatty-liver-pregnancy-aflp-need-566729.html?cat=70. [Accessed 15 January 13].
Wikipedia, the free encyclopedia. 2012. Acute fatty liver of pregnancy. [ONLINE]  Available at: http://en.wikipedia.org/wiki/Acute_fatty_liver_of_pregnancy. [Accessed 15 January 2013].
University of Rochester Medical Center . 2013. Acute Fatty Liver of Pregnancy.[ONLINE] Available at: http://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=90&ContentID=P02465. [Accessed 15 January 2013].
National Digestive Diseases Information Clearinghouse . 2013.Liver Biopsy. [ONLINE] Available at:http://digestive.niddk.nih.gov/ddiseases/pubs/liverbiopsy/. [Accessed 15 January 2013].
Medscape: Medscape Access. 2013. Treatment-show all. [ONLINE] Available at: http://emedicine.medscape.com/article/1562425-treatment#showall. [Accessed 19 January 2013].

Causes of AFLP

The general cause of AFLP is unknown, but it is believed to be caused by an autosomal recessive Fatty Acid Oxidation Defect (FAOD) known as LCHAD (Long Chain 3-Hydroxyacyl-CoA Dehydrogenase) deficiency in the fetus. LCHAD, an enzyme in the mitochondria, is responsible for the beta-oxidation of  long-chain fatty acids to give energy.

A deficiency of LCHAD would result in the liver's inability to oxidise these long-chain fatty acids, which blocks the body's energy supply. These unoxidised fatty acids may accumulate in the liver, heart and kidneys and disrupt their functions. It also causes the liver to produce acid to break down the fatty acids, which attacks the mother's and fetus' organs.

AFLP may result in a mother who is a heterozygous carrier of the LCHAD enzyme deficiency and whose unborn child has the same condition.

Source: http://www.socialstyrelsen.se/rarediseases/lchaddeficiency

 If left untreated, AFLP can cause liver failure, which may result in a need for a liver transplant or death. Babies whose mothers have AFLP may also die from cardiac arrest and Hypoxic Ischemic Encephalopathy, which cuts of oxygen supply from the brain, leading to extensive brain damage.





References:
The Swedish Information Centre for Rare Diseases.2011. LCHAD deficiency. [ONLINE] Available at:http://www.socialstyrelsen.se/rarediseases/lchaddeficiency. [Accessed 15 January 2013]
Rachel Slaugh. 1995. Discription of Disorders. [ONLINE] Available at: http://www.fodsupport.org/lchad.htm. [Accessed 15 January 2013].
N Engl J Med .1997. Liver Diseases in Pregnancy. [ONLINE} Available at:http://www.nejm.org/doi/full/10.1056/NEJM199701303360514#t=article. [Accessed 15 January 2013]
Kansas- Department of Health and Environment. 2013. Long Chain 3-hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency Information for Healthcare Professionals. [ONLINE] Available at:http://www.kdheks.gov/newborn_screening/download/ACT/LCHADD_Info_for_Health_Professionals.pdf. [Accessed 15 January 2013].
Marjorie Nimis. 2013. About AFLP. [ONLINE] Available at:http://www.acutefattyliverofpregnancy.co.uk/pageID_7446872.html. [Accessed 15 January 2013].

The Biochemistry of AFLP: Fatty Acid Beta-Oxidation

source: http://lipidlibrary.aocs.org/animbio/fa-oxid/index.htm

As mentioned before, AFLP is thought to be caused by the deficiency of LCHAD (Long-Chain 3-hydroxyacyl-enzyme A dehydrogenase, or 3-hydroxy acyl CoA dehydrogenase as shown in the diagram) , an enzyme that is involved in the beta-oxidation of long-chain  fatty acids in the mitochondria.

Beta-Oxidation is the process of converting large fatty acid molecules into simpler, smaller molecules of acetyl CoA, with the release of FADH2 and NADH, which are used to produce ATP (the energy currency of the body) through the Electron Transport Chain.

When a pregnant woman suffers from AFLP, the enzyme LCHAD is deficient, or absent in the fetus. Thus, L-3-hydroxy acyl CoA cannot be converted to a smaller 3-ketoacyl CoA, which is simpler, smaller ketone body. Without this conversion, the L-3-hydroxy acyl CoA would accumulate in the liver, heart and kidneys, causing disruptions in their function and may lead to other liver function complications.






References:

Fillmore, N., Alrob, O. A., Lopaschuk, G. D., 2011. Fatty Acid β-Oxidation. [ONLINE] Available at: <http://lipidlibrary.aocs.org/animbio/fa-oxid/index.htm> [Accessed 17 January 2013]

Cardiomyopathies. 2012. Cardiomyopathies-Genetic. [ONLINE] Available at:http://neuromuscular.wustl.edu/msys/cardiac2.htm. [Accessed 15 January 2013].

Symptoms of AFLP

Symptoms of AFLP will start to surface around the third trimester of pregnancy. Some symptoms of AFLP may seem similar to other pregnancy complications.

Signs and Symptoms:

•  Severe nausea and vomiting
•  Abdominal pain, especially at upper-abdomen
•  Malaise (general discomfort)
•  Headache
•  Jaundice (yellow colouring of skin, eyes, and mucous membrane)
•  Fever
•  Hypoglycemia
•  Pancreatitis
•  Altered mental state
•  Liver failure - if condition is serious
•  Coagulation 
• Encephalopathy (brain disorder) - may occur in babies. An example will be the babies from the case study in which one of the twins passed away due to severe encephalopathy.

https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjJgGo18D_P7XYzUFIfJoJrD1t_mSIxiTb1nWNqWnSUQbiy0nxW7JZhy9rd5WVy3e3ce_KUYVEyT30xWVgqTjgvzHdezomaX7dgbp79AvQsflz76gMEwRJOC3nVS30PgHskVFciX2zpv80/s200/vomiting.jpg

                                   

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https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiYfGD4ci-uBZukioe2RCfi5eN72D8gZQDMlkLAUTk_TNgt6mw-GWLyMp3cD1BceBv-fvEwr4zTFa3nWNHrJGQsSM0OB9Y0SQXrT-rjrm5KVCnGuiCylmuNhfARKDyXUX82EX63TYZQj9Y/s1600/headache.jpg

AFLP can also be associated with other conditions such as pre-eclampsia and diabetes insipidus (water diabetes) -which can lead to frequent thirst and increased urination.






*NOTE
Symptoms of AFLP may differ in different people.Many other conditions also maybe associated with AFLP depending on how serious is each case.
Always consult the doctor when you feel unwell during your pregnancy.  

References: 

March of Dimes. 2008. Liver disorders. [ONLINE] Available at:http://www.marchofdimes.com/pregnancy/complications_liver.html. [Accessed 17 January 2013].

University of Rochester Medical Center. 2013. Acute Fatty Liver of Pregnancy. [ONLINE] Available at: http://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=90&ContentID=P02465. [Accessed 17 January 2013].
Marjorie Nimis. 2013. Acute Fatty Liver of Pregnancy - About AFLP. [ONLINE] Available at:http://www.acutefattyliverofpregnancy.co.uk/pageID_7446872.html. [Accessed 17 January 2013].
Richard Sammons, (2008), Acute Fatty Liver of Pregnancy [ONLINE]. Available at:http://www.acutefattyliverofpregnancy.co.uk/mediapool/76/765711/data/2008.05.12_-_Daily_Mirror_-_Richard_1_.jpg [Accessed 19 January 13].
Sarah A. 2007. Acute Fatty Liver of Pregnancy (AFLP): What You Need to Know. [ONLINE] Available at:http://voices.yahoo.com/acute-fatty-liver-pregnancy-aflp-need-566729.html?cat=70. [Accessed 19 January 13].
Medscape: Medscape Access. 2013. Presentation-show all. [ONLINE] Available at: http://emedicine.medscape.com/article/1562425-clinical#showall. [Accessed 19 January 2013].

Additional info : Case Study of AFLP

This is a summarize case study on a mother that had AFLP when carrying a twin boy babies, however her condition is unlikely to be caused by genetic as she did not mentioned any similar cases occurring in her family history. Below also show the some symptoms that a patient of AFLP will have...

 left- Sasha, right- Micah (Both 5 days old then)
[https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgmf8hciIUuj3s7fIKZxqIO98jVsRbBkoycLRsb0rAmzttrH6kfF93n6zm5oCm5Fi9DGaQj06U5NO7EVcwMBkyotBoZyKgrYT0DXy72alhntVGfaD7l9OLfpMIG8yJN5vFwuwhkpsSTqp0/s320/babies.jpg]

                                 
Majorie Nimis, a British woman, was diagnosed with AFLP in early 2005 when she was 26. She was pregnant for the first time carrying twin boys. She gave birth to the twins, Micah and Sasha at 37 weeks. However, Micah passed away after six days due to severe neonatal encephalopathy. He had fit and never regain consciousness. Sasha, on the other hand, survived with moderate neonatal encephalopathy but suffers from cerebral palsy (a kind of impaired brain development) in which he requires long-term treatment and therapy.

Majorie initially suffered from common pregnancy complications such as nausea, vomiting and dry mouth. However, by the 35th week, her condition worsened. Her fluid intake increased to 10 liters per day and another 3 liters per night, yet she still felt thirsty. She also had dry, itchy skin, heartburn and could not consume 'normal' food as she felt that the food was too dry.

By 36 weeks, Majorie woke up with a half-paralyzed face as the muscles became slack. She was taken to hospital and was diagnosed with Bell's Palsy. She became oblivious to her surroundings, felt lethargic all the time and loss her appetite. She also had been vomiting frequently for days and had abdominal cramps.

Majorie after giving birth
[https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiop_TPuApUDjzvtYlW3JrNtiKN3LvnxjS1OnYwNzkoMk1HHLHCOrppPPBdwo8kn33uAYughm8ojd1I3lvW8qARVhzNreIF4iIFL0BJh9d8xUy-zlSEu-D1M51tGxvFHLQZb8ipFSlDrgU/s1600/mjj.JPG]

By 37 weeks, her water bag broke and she only had 50-50 chance of survivial. Since she was unfit for normal birth, she had cesarean section. However, this was not the end of her sufferings. She was diagnosed with AFLP following a liver function test that showed its cause for her abnormal symptoms such as comatose state, the babies'cardiac arrests, becoming jaundiced and swollen after cesarean. Due to AFLP, she had problems with blood clotting, and was also diagnosed with Diabetes Insipidus (water diabetes) that caused her increased fluid intake and constant thirst. And that despite her huge fluid intake, she was dehydrated and put in HDU (High Dependency Unit) for 24 hours.

Both Majorie and Sasha have recovered from the incident and are now healthy. Majorie went on to have 3 more healthy children which fulfill her dream of having 4 children, while Sasha is receiving hydrotherapy, physiotherapy and other treatments for his long term condition.

Majorie with her subsequent children
[https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiAiSWu8XlqsRW_pOxXuV7lBw2PWXY4Zugnc-OUUTk7Qe0z_8mV95XwgkQ9BMo8CxjcZbL-V_Zz0NaT-1vajAaWHgn_sMk90PaOs67K9kVqsWxZezugcigdhDshbKpUI3aY9TMP6bMyQuU/s1600/mj.jpg]

Sasha around 2 years old
[https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhAC8rigtAMRwa_F_vqLRTvwhM192wGCsEVvK_zG2zWArA1KgRqORSEaEHtWv8bkPB0kVqFeTO3XwWKwK9Tm0Jbq7lz94BNLezoqW6tVjsbQ5x1NtcFtZeoabGCt9c3VgCJOIqOlgQujPU/s320/sasha.jpg]

References:
Marjorie Nimis. 2008. [ONLINE] Available at:http://www.acutefattyliverofpregnancy.co.uk/mediapool/76/765711/data/Marjorie_-_BJM_-_April_2008.pdf. [Accessed 17 January 2013].
ITV1. (2007). Interview with ITV on "This Morning" with Phil and Fern. [Online Video]. 15 October. Available from: http://www.acutefattyliverofpregnancy.co.uk/pageID_7446878.html. [Accessed: 17 January 2013].

Interview with ITV on "This Morning" with Phil and Fern

This is an interview shown on ITV in 2007 about the case study of AFLP occured on Majorie Nimis

Reference:

ITV1. (2007). Interview with ITV on "This Morning" with Phil and Fern. [Online Video]. 15 October. Available from: http://www.acutefattyliverofpregnancy.co.uk/pageID_7446878.html. [Accessed: 17 January 2013].