 Introduction

 Familial lipoprotein lipase deficiency is a rare genetic disorder in which a

person is unable to produce enough lipoprotein lipase, the enzyme which
breaks down fats that enter the bloodstream after a meal (chylomicrons).
 Deficiency of this enzyme results in pronounced accumulation of triglycerides
in the plasma
 High triglyceride levels are present from infancy and childhood, and various
associated symptoms may occur
 Familial LPL deficiency affects males and females in equal numbers. Based on
recent data (2013), it is estimated to occur in approximately 1 in 250,000
people in the general population and has been described in all races.
 The prevalence is much higher in Quebec ( ), Canada due to a founder
effect. A founder effect is when a small isolated population of settlers
(founders) expands over several generations leading to a high prevalence of a
particular genetic trait.

 Symptoms and Signs

 Most cases of familial LPL deficiency are identified during childhood, usually
before the age of 10. In approximately 25 percent of cases, the disorder is
identified during the first year of life. Some cases may not be identified until
adulthood.

 The main symptoms are

1) abdominal pain

- The severity of abdominal pain can vary, ranging from mild to severe and, in
some cases, can be incapacitating.

- The pain may be located in the upper, central region (epigastric area) of the
abdomen and can radiate to cause back pain.

- In some cases, the pain may be widespread (diffuse) and can potentially
resemble acute abdomen (peritonitis).

- Abdominal pain in individuals with familial LPL deficiency may result from
recurrent episodes of inflammation of the pancreas (pancreatitis).
2) Pancreatitis
- The main symptom of pancreatitis is
 Pain; which is sometimes intense, and is most often felt in the upper left
side or middle of the abdomen.
 nausea,
 sweating,
 weakness,
 chills,
 clammy skin,
 mild yellowing of the skin or whites of the eyes (jaundice).

- Some individuals will develop acute, recurrent pancreatitis, which can

potentially be lethal.

- Chronic pancreatitis can be associated with additional complications

including
 diabetes,
 hardening of the pancreas (pancreatic calcification) stools containing
excess amounts of fat causing them to be frothy, foul smelling and to float
(steatorrhea).
- However, these complications are unusual in individuals with familial LPL
deficiency. Even in individuals with recurrent episodes of pancreatitis, such
complications rarely develop until middle age.

- Although rare, pancreatitis in LPL deficiency can cause severe, life-

threatening complications

3) eruptive xanthomas
- Approximately 50 percent of affected individuals develop eruptive cutaneous
xanthomas, which are skin lesions make up of certain fats (lipids).

- Xanthomas may appear as raised, reddish-yellow bumps or nodules on the

skin. They often occur on the buttocks, knees and outer arms. Individuals
lesions may measure about 1 millimeter in size, but xanthomas often cluster
and may grow together (coalesce) to form larger lesions.
- Eruptive xanthomas are generally not painful or tender, unless they develop
on an area of the body where they suffer repeated trauma or abrasion.

- Xanthomas usually appear within a few days after triglyceride levels in the
plasma have begun to increase. They may contain a greasy, yellowish
substance and sometimes a milky fluid.

- Xanthomas will disappear over a period of weeks to months as the amount of

triglyceride in the plasma decreases.

- The persistent presence of xanthomas in individuals with familial LPL

deficiency indicates inadequate therapy to lower triglyceride levels.

4) Hepatosplenomegaly
- Enlargement of the liver and spleen (hepatosplenomegaly) can also occur,
especially in infants and young children.

- The degree of enlargement varies, often in conjunction with the amount of

fat in the diet

- As fat levels rise, certain white blood cells called macrophages take in excess
fat in an attempt to rid fat from the bloodstream. After taking in fat, the
macrophages travel to the liver and spleen, where the fatty cells accumulate.
Note:- The blood of people with familial lipoprotein lipase deficiency can have a
milky appearance due to its high fat content

5) Other symptoms:-
 lipemia retinalis
- In the presence of excessive fatty substances in the circulation the small
arteries (arterioles) and small veins (venules) in the outer parts of the retina
and the back of the eyeball (fundus) may appear pale pink upon examination
by an eye specialist (ophthalmologist). This condition may be referred to as
"lipemia retinalis".

- The change is related to the degree of fatty build up (i.e., large

chylomicrons),.which causes incoming light to scatter.

- Lipemia retinalis can develop when triglyceride levels exceed 4000 mg/ dL
- This discoloration is reversible and does not affect the vision of individuals
with familial LPL deficiency.

 neurological features
In some cases, additional symptoms have been reported in individuals with
familial LPL deficiency including a variety of neurological features
including
 depression,
 memory loss
 dementia.

Notes:-
- The most common symptom of familial LPL deficiency is episodic abdominal
pain.

- LPLD is generally not associated with an increased risk of atherosclerotic

vascular disease.

 Causes
 Familial LPL deficiency is caused by mutations of the LPL gene. This genetic
mutation is inherited as an autosomal recessive trait.

 Genetic diseases are determined by the combination of genes for a particular

trait that are on the chromosomes received from the father and the mother.

 How did I get it?

- LPLD is an autosomal recessive condition. This means that to have LPLD
you need to have inherited two faulty LPL genes (one from your mother
and one from your father).

- Having one altered LPL gene does not result in LPLD – this is the meaning
of the word ‘recessive’.

 What are the chances of passing it on?

1. If both parents are carriers:
Each child born to parents who are both carriers of the altered gene will have
 - A 25% chance (1 in 4) of developing the condition (i.e. the pair of genes
they inherited would have been the disease causing gene from both
parents)

- A 50% chance (1 in 2) of being carriers of the disease (the disease-causing

gene plus the healthy gene, one from each parent)

- A 25% chance (1 in 4) of being completely clear of the disease (inheriting

the healthy gene from each parent)

2. If one parent has LPLD :-

Individuals with the condition will have two disease-carrying genes

If they have a child with a partner who is a carrier each child will have a 50%
chance (1 in 2) of having the condition, and a 50% chance (1 in 2) of being
a carrier

 If I am a carrier does it affect my health?

People who are carriers for this condition will not present any problems but
may have mildly raised blood fat levels

 Diagnosis
 A diagnosis of familial LPL deficiency may be suspected based upon
identification of
1. characteristic symptoms,
2. a detailed patient history,
3. a thorough clinical evaluation
4. certain tests including blood tests.

Clinical Testing and Workup

1. Blood tests can reveal reduced activity of the lipoprotein lipase enzyme in
the plasma, following intravenous administration of heparin. Heparin is a
substance normally found in the liver that stimulates the release of
lipoprotein lipase in the body.
 2. A diagnosis of familial LPL deficiency can be confirmed by the molecular
genetic testing for mutations in the LPL gene.

 Treatment
- Treatment aims to control the symptoms and blood triglyceride levels with a
very low-fat diet.
- you should eat no more than 20 grams of fat per day to prevent the
symptoms from coming back
- Twenty grams of fat is equal to one of the following:

 2 8ounce (240 milliliters) glasses of whole milk

 4 teaspoons (20 grams) of margarine
 4 ounces (112 grams) serving of meat

.Note:- healthy level of fat intake (in the UK) is considered to be no more than
70g a day for women and 95g for men (The average daily intake of lipids by U.S.
adults is about 81 g,)

Recommends:-

- Fatsoluble vitamins A, D,E, and K and mineral supplements are

recommended for people who eat a very lowfat diet.

Drugs that lower lipid levels in the body are not effective in reducing fat levels in
individuals with familial LPL deficiency

- Alcohol and drugs that increase triglyceride levels should be avoided.

Prevention
There is no known prevention for this rare, inherited disorder. Awareness of
risks may allow early detection.