تشخیص

Familial chylomicronemia syndrom

TG   =  24000

CHOL  = 1600

Lipoprotein electrophoresis :

 chyl = 40%      ( 0 % )

LDL = 41%       (40-60%)

VLDL = 15%     (15-25%)

HDL = 4%         (25-35%)

Disorders of lipoprotein metabolism

Children with elevated chol Level should be identified early in life to try to reduce the associated risk of heart dis.

Adult cardiovascular dis has its roots in childhood

Hyper chol. : > 75th percentile for the age & sex

Hyper TG >95TH  percentile for age & sex

Hyper TG is also a risk factor for premature CHD , the risk is less well defined than hyper CHOL.

Primary prevention of CHD is important

Plasma lipoprotein metabolism & transport

Plasma lipid & lipoprotein levels

During the first few month of life , chol increase largely  Because of changes in LDL.

HDL CHOL are compatible in M & F early in life but decline markedly in M during the 2th decade

TG rise transiently in M & F in the first year ,fall to a  mean 50-60 in the few years & then rise by age 20yr.

Screening for hyper CHOL.

Parental CHOL > 240 mg/dl

Children with incomplete or un available FHX.

Other risk factors for CHD ( obesity ,cigarette smoking , HTN, DM,  inactivity, low HDL)

Total chol < 170 mg/dl : re-evaluated in 5yr

Total CHOL > 200mg/dl : fasting lipid profile

Total CHOL 170-199 MG/DL : another CHOL measurement

 positive FHx  Of Premature coronary heart dis. : lipid profile

Lipid profile ( total & HDL CHOL, calculated LDL CHOL ) after a 12 hr fast

LDL CHOL= total chol – [HDL+ ( TG/5)]

Treatment of hyperlipidemia

Dietary management

For child with average LDL CHOL > 110 mg/dl older than 2yr is the best initial Intervention

Step 1 diet :

fat < 30% total cal. < 100 mg chol/1000 cal ( max 300 mg/24hr) 

Minimal goal : LDL< 130 , ideal goal: LDL<110

Step 2 in diet :

Fat < 20% total cal.  < 7% calories as saturated fat , < 66 mg chol /1000cal ( max 200 mg/24hr)

Response to dietary management : variable & < 10-15%

Children < 2yr require a relatively large amount of cal maintain their rapid growth 

Total caloric content

Wt loss in overweight individuals

Adverse effect in extreme dietary changes ( ↓ essential nutrients -  electrolyte abnormalities , orthostatic dizziness, GE discomfort , headache, cold intolerance , menstural irregularities, peripheral neuropathy)

Sudden cardiac death

Yo-yo dieting

Nutritional composition

↑ intake vegetable fruits cereals & other  complex carbohydrate sources

Saturated fat : ↑ total Cho& LDL ,↓ HDL

Polyunsaturated fat : ↓LDL, HDL↓

Monounsaturated fat :↓LDL, NLor↑ HDL

Soluble dietary fiber : ↓VLDL ,↓ LDL

Dietary supplement

Plant sterols ( 2 gr daily) : ↓LDL ( 10 to 13 % )

Fish oils : ↓ TG & anti PLT benefits

Physical activity

Regular physical activity

Moderate  physical activity( expand a minimum of 200 kcal/day)

Improve lipoprotein profiles

Long term is most effective

30 to 60 minutes for 4 to 6 times/week

Walking, swimming, bicycling , jogging

Drug therapy

Child >= 10yr after a adequate trial of diet therapy :

LDL remains > 190 mg/dl

LDL > 160 mg/dl &

positive FHX of premature CHD

Two or more other risk factors ( DM ,HTN , smoking, low HDL, sever obesity , physical inactivity )

Secondary hyper lipidemia

Most of the hyper TG & hyper chol is secondary to exogenous factors or underlying clinical disorders

Obesity , hypothyroidism , DM, nephrotic synd. ,renal failure, GSD, tay sachs, niemanpick, congenital biliary atresie , SLE 

Thiazid diuretics , steroid , beta drenergic blocking agent , immunosuppressants

Primary ( genetic) dyslipidemia

frederickson classification

Disorder associated with hyperchol. & severely elevated  TG ( > 1000 mg/dl )

Fasting TG > 1000 mg/dl in children reflect sever hyperchylomicronemia & indicate an underlying  genetic disorder

The major clinical compilication is acute pancretitis

Familial chylomicronemia synd.

AR

LPL or apoc-2 deficiency ,Approximately  1/1 million person

May be evident as early as 2 days

May be silent & discovered incidentally ( lactescent blood)

The most common clinical presentation is acute , recurrent episodes of abdominal pain

The age quite variable

Pains may be  vary from mild infantile colic to severe peritonitis

Generalized or localized

Spasm , rigidity or rebound tenderness

Fever or leukocytosis → surgical intervention (usually a milky exudate un the peritoneal cavity is the only finding)

Anorexia

Abd. Tenderness

Vomiting

Diarrhea

 acute panceratitis

Well recognized complication

Sever abdominal pain

Hypotension

Sweating

Shock

Pancreatic necrosis without calcification

The serum amylase level may be very high or normal

TG > 1000 mg/dl

Infants & children with recurrent abdominal pain & pancreatitis & familial pancreatitis should be examined for hyper chylomicronemia

Hepatosplenomegaly

Ingestion chylo by the RE SYSTEM

Particularly prominent in infants & children

Decrease of size within 24 to 48 hrs of initiation of the fat free diet

Sometimes pain due to splenomegaly

Fat embolism

Seizure , transient paralysis

GI bleeding

Cutaneous eruptive xanthoma

In about 50% of pts

On the buttoks ,back,proximal of the extremities and extensor surfaces

Yellow or yellow center

1-5 mm in diameter

Neither painful nor pruritic

TG >2000

Complete disappearance may take as long as 3 wk

Lipemia retinalis

Characteristic  of  long standing hyperlipidemia

Whitish or pinkish discoloration

Rarely wite diposits of lipid in retina

 micro aneurysm & hemorrhages

Intermittent swelling of the scrotum

Milky effusion in tunica vaginalis

Swelling & mottling of the legs

Anemia , leukopenia & persistent thrombocytopenia

The very high  lipid produce artefactual lowering of the values of many solutes

The degree of error is approximately 1% for each 0.9% gr/dl TG

Do not have hyperuricemia & abnormal GLU. Tolerance

Diagnosis

Based on the clinical presentation & some key lab features

Plasma is lactescent

TG> 1000 mg/dl may be as high as 15000 mg/dl

Total CHOL levels are elevated

CHOL/TG ratio always less than 0.2 & often less than 0.1

Refrigerator test ( 18-24 hr at 4 c) : cake of chylomicrons forms on the surface & inferanatal  layer is clear

Lipoprotein electerophoresis : marked elevated chylo.

DX. Can be confirmed by quantitation LPL activity in plasma after IV heparin injected

LPL activity of about 50% of normal in parents

Heterozygote may have hyper TG but fasting levels of TG are usually NL or near NL 

 TREATMENT

Restriction of total dietary fat

Most recommendations : TG < 1000 or even < 750 mg/dl

There is no specific problem with saturated or unsaturated fat

Total  fat < 15%  or 10% of daily calories

0.5 gr/kg useful in initiating therapy in children

 caloric supplementation with medium-chain TG can be useful

No single meal should contain more than 20 gr of fat

Management is very difficult & TG may rise suddenly from a few hundred to  several thousand mg/dl following a single fat filled meal

If necessary , TG lowering medications (niacin or fibrates or fish oil) may be added

FFP  in APOC -2  deficiency

 Type V hyperlipoproteinemia (HPL)

Common in adult

DX. With TG>1000 mg/dl without  LPL or apoc- 2 deficiency

Acute pancreatitis

Positive FHX.  Of hyper TG

DM or GLU. Intolerance

Nephrotic synd

Esterogen  therapy , heavy alcohol use 

Discontinue of drugs  that exacerbate hypre TG

Control of underlying dis.

Dietary management

 regular aerobic exercise

Drug therapy