Severe combined hypercholesterolemia & hypertriglyceridemia, TG disorder

Case submitted from:

Irwin Benuck, MD, PhD

Division Head, Community Based General Pediatrics

Professor of Pediatrics, Northwestern University Feinberg School of Medicine

A 2 ½ month old Asian American male, previously in good health, was referred by his pediatrician to the emergency room with fever and URI symptoms. A PCR nasal swab in the ER confirmed coronavirus.  During the ED workup, blood was drawn and appeared milky.  Both TC and TG were greatly elevated.  He was admitted for further evaluation and treatment. 

Additional current hx:  Had been growing well since birth, but more fussy than older child had been.  Father reported the patient seemed uncomfortable in his sleep.  Stools yellow water, seedy consistent with breast milk fed baby.  Taking 6 ounces per feeding.  No blood in stools.  At least 5 wet diapers per day. 

Pertinent Family history:  No parental consanguinity.

Brother 4 yrs old and well, has not had lipids checked.  Has occasional abdominal pain.

Father 36, mother 37, no known lipids disorders and both believe they have had their lipids checked. 

No family history of abdominal pain, pancreatitis, coronary artery disease, sudden death or stroke.   + Grandparents x 3 with mildly elevated lipids but all diet controlled.  + type 2 DM diet controlled in 1 grandparent.

PMH:  7 lbs, 5 oz, term.  No complications of pregnancy or delivery.

Diet:  Breast fed

Immunizations up to date (Hep B x 2)

PE: He is alert and active: Height, Weight, Head Circumference all at 85th percentiles.  His VS are all normal. 

HEENT: Normocephalic

CARDIO/PUl: Chest is clear A and P, with normal S1, S2, no S3 or S4 and no murmur

ABDOMEN: Moderately distended with small umbilical hernia easily reducible.  Spleen 1 CM below LCM.  Liver edge palpated right below RCM.  He appears somewhat tender in upper quadrants.

NEURO: Intact with normal muscle tone

SKIN; No Xanthomas or other lesions.

Eyes:  Ophthalmology consulted and diagnosed with lipemia retinalis.

Abdominal U/S:

Mild enlargement and possible heterogeneous echotexture in the pancreatic head and and proximal body. Consider clinical/laboratory correlation for pancreatitis.

Spleen is large for age.

Echocardiogram:  Unremarkable

CXR:  cannot rule out subtle pneumonic infiltrate

Labs on admission:  TC 1282, TG >5000, LDL not able to calculate, HDL 49,

Creatinine 0.22, Glucose 135, Liver panel normal

Initial Peds Preventive Cardiology Impression: Very interesting patient with severe combined hypercholesterolemia and hypertriglyceridemia. This appears to be a gene defect in the breakdown of chylomicrons. Could be LPL defect or other genes in the lipolysis of TG-rich lipoproteins. Our immediate concern is the elevated TG and how to bring this down rapidly as this can cause pancreatitis. Networking with experts in the field, it is best at this time to put patient on a very low fat formula which was started yesterday. Per parents, he seems more comfortable than he has been in a long time. Cholesterol levels should fall as TG falls. Fish oil and fenofibrate medication may not be beneficial. Plasmapheresis is an option but should be deferred to first assess success of low fat formula. Genetic testing for LPL, APOC2, APOA5, GPIHP1, LMF1, or GPD1 genes can be done in future at special lab in Canada. He appears happier today and able to palpate abdomen with no pain illicit. His lipase is also improved.

Hospital Course:  Breast feeding was stopped and he was given Provimin formula (low fat) with added walnut oil ad lib.  His lipase improved as well as TC and TG. (TC 658, TG 3299, HDL-C 25, LDL-c not able to calculate).  His formula was changed because of insurance issues and was discharged with Monogen formula (also low fat formula) with added walnut oil ad lib. 

His pneumonia was also treated with PO amoxicillin.

Readmission:  He was doing well at home when noticed urticarial rash.  He was readmitted to PICU for observation and determine if allergic to the formula or amoxicillin.  He tested positive to milk protein and formula was switched to Vivonex with walnut oil.  He was discharged home and appears to be doing well.  We will reevaluate the lipids at the next visit to Preventive Cardiology. 

Follow-up:  He will be followed in both Genetics and Preventive Cardiology.  We made contact with Dr. Hegele in Western Canada who was very helpful with diet and offered support with further genetic testing.