For medical students , it will help. Especially for preclinical students, as early clinical exposure, it will be very useful. Even for theory exam, it will help.

1. Clinical cases
Lipid metabolism
DR.S.SETHUPATHY, M.D,PH.D

2. Case 1
 An 8 year-old girl complained of hypotonia, skeletal
muscle weakness, exercise intolerance. Hepatomegaly
was present. She was investigated.
 Hemoglobin- 12 .2 gm/dl ( 11.2 – 14.5 gm/dl)
 Plasma glucose- (Random) - 52 mg/dl.
 Urine ketone bodies negative
 Serum lactate – 32 mg/dl ( 4.5 – 20 mg/dl)
 Serum total CPK- 420 mcg/L (10 to 120
micrograms per liter (mcg/L)

3.  Lipid profile - Serum total cholesterol – 232 mg/dl (140-200 mg/dl)
 Serum triglycerides – 174 mg/dl ( 50 -150 mg /dl)
 Serum LDL - 149 mg/dl ( < 100 mg/dl)
 Serum HDL 48 mg/dl ( 45 -60 mg/dl)
 Histochemical investigation revealed abnormal accumulations of lipid
between the myofibrils.
 Serum bilirubin- 1.6 mg/dl (<1 mg/dl)
 AST - 76 U/L ( <40 u/L)
 ALT - 92 U/L ( < 40 U/L)
 ALP - 122 U/L ( <40 - 150 U/L)

4. Either transport defect or oxidation
defect
 Lack of energy – lesser oxygen, Glucose, fatty acids
 During fasting, beta-oxidation of fatty acids provides the necessary energy.
 Carnitine is required in the transfer of long-chain fatty acids across the
inner mitochondrial membrane for beta-oxidation.
 When fatty acids cannot be utilized, glucose is consumed.
 It results in Nonketotic hypoglycemia.
 Glycolysis and OxPhos steadily operate and provides large amount of
energy than glycolysis alone. As glucose rapidly undergoes glycolysis
beyond the capacity of OxPhos, pyruvate accumulates which gets reduced
to lactate causing lactic acidosis.
 Serum carnitine - 6 μmol/L ( 28-60 μmol/L)- deficiency

5. Case 2
• A 24 year old, primigravida ( gestational age- 37
weeks)complained of nausea , vomiting and malaise.
• On examination- Jaundiced , anemic
• BP – 160-100 mm of Hg.
• Investigations
• Hb – 10.9 g/dl
• RBC - 3.2 ( 4-6 millions /micro l)
• WBC – 15400 (4500 – 11000 / micro l)
• Platelet - 90000 ( 150000 – 450000 per micro l)
• Plasma glucose – 55 mg/dl

6.  Serum bilirubin- 3.6 mg/dl (<1 mg/dl)
 AST - 96 U/L ( <40 u/L)
 ALT - 122 U/L ( < 40 U/L)
 ALP - 172 U/L ( 40 – 150 U/L)
 Clotting time 162 seconds (70 to 120 seconds)
 Prothrombin time – 18 secs (10 -14 seconds)
 PT-INR - 2.4 ( 1-1.5 )
 Plasma ammonia - 52 (15 to 45 µ/dL )
 Plasma fibrinogen - 162 (200 to 400 mg/dL)
 HbsAg - negative

7. Liver biopsy
 A liver biopsy can provide a definitive diagnosis but due to the
increased chance of bleeding mostly not done in acute fatty
liver of pregnancy
 Other causes of liver dysfunction- viral hepatitis, drug-induced
liver dysfunction, and acetaminophen poisoning, Reye’s
syndrome, pre-eclampsia, HELLP syndrome,intrahepatic
cholestasis of pregnancy, autoimmune hepatitis should be
ruled out.

8.  An accumulation of medium and long chain fatty acids occurs in
the fetus. The unmetabolized fatty acids will re-enter the maternal
circulation through the placenta, and overwhelm the beta-oxidation
enzymes of the mother. It results in accumulation fat in the liver.
 The gene responsible for LCHAD is isolated and the most common
mutation found in acute fatty liver of pregnancy is the
E474Q missense mutation.
 Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
is A.R in inheritance and mothers are often found to
be heterozygous for the affected mutation.
 Acute fatty liver of pregnancy

9. Case 3
 A 62 year old man complained of passing foul smelling, bulky,
frothy stools which floats for the past one month. He also
complained of weight loss. No vomiting, no loss of appetite.
 On examination - anemic, not jaundiced
 Investigations
 Hb – 10.9 g/dl
 RBC - 3.2 ( 4-6 millions /micro l)
 WBC – 8400 (4500 – 11000 / micro l)
 Platelet - 175000 ( 150000 – 450000 per micro l)
 Plasma glucose – 92 mg/dl

10.  Serum bilirubin- 0.9 mg/dl (<1 mg/dl)
 AST - 32 U/L ( <40 u/L)
 ALT - 12 U/L ( < 40 U/L)
 ALP - 78 ( 40 -150 U/L)
 Serum total proteins – 5.1 g/dl ( 6-8 gm/dl)
 Albumin - 2.8 g/dl ( 3.5 -4.5 g/dl)
 Fecal fat excretion - 48 g / three days ( 6 - 21 g /three days)
 Serum calcium – 7.8 mg/dl ( 9-11 mg/dl )
 Serum phosphorus - 3.1 mg/dl ( 3.5 – 4.5 mg/dl)
 Serum alkaline phosphatase - 180 ( 40- 140 U/l )
 25-hydroxy cholecalciterol - 24 (30 -50 ng/l)

11. Defective digestion or defective absorption
 D-xylose absorption test – It is absorbed across the intestinal
mucosa After a patient drinks the Xylose, urine or blood are
collected over the next several hours.
 Low Xylose levels in the blood or urine are highly suggestive
of an abnormality of the intestinal mucosa.
 Bentiromide test – Bentiromide chemical is given. This is
broken down by pancreatic enzymes and
(paraaminobenzoicacid, PABA) is released which is absorbed
and excreted in the urine.
 Pancreatic insufficiency is suspected when urinary PABA levels
are low.

12. Case 4
 A recently diagnosed diabetic male patient came for regular
check up and got investigated- Blood pressure - 140/96
mm of Hg
 Plasma glucose ( Fasting) - 160 mg/dl
 Plasma glucose ( Post prandial) - 280 mg/dl
 Urine glucose – Post prandial – 3+
 Spot Urine albumin Creatinine ratio - 25 ( less than 30
microg/mg – normal , 30 – 300 – microalbuminuria, > 300
micro g/mg – albuminuria)
 HbA1c - 7.2 % (< 6 – normal, 6-6.4 prediabetes, > 6.5 –
diabetes)

13. Lipid profile
 Serum total cholesterol – 227 mg/dl (140-200
mg/dl)
 Serum triglycerides – 184 mg/dl ( 50 -150 mg /dl)
 Serum LDL - 114 mg/dl ( < 100 mg/dl)
 Serum HDL 42 mg/dl ( 40 -60 mg/dl)
Renal profile
 Serum urea - 24 mg/dl ( 15-40 mg/dl)
 Serum creatinine - 0.9 mg/dl ( 0.6 – 1.2 mg/dl)
 Serum uric acid - 5.2 mg/dl ( 4- 7 mg/dl)

14. Serum electrolytes
 Serum sodium - 138 (135-145 mmol/l)
 Serum potassium - 4.1 (3.5- 5.0 mmol/l)
 Serum chloride- 98 ( 96-106 mmol/l)
 Serum bicarbonate - 24 ( 22-29 mmol/l)

15. Interpret the results
Blood glucose – elevated - Both F&PP
HbA1c - increased
Uncontrolled diabetes
Urine albumin creatinine ratio – normal
No nephropathy
Serum Total Cholesterol, TGL, LDL cholesterol elevated
HDL cholesterol- normal
Hypercholesterolemia

16. Treatment for hypercholesterolemia
 Statin group of drugs - Atorvastatin, Rosuvastatin
 Mechanism – HMG CoA reductase inhibition
 Rate limiting enzyme of cholesterol biosynthesis –
HMG CoA reductase
How cholesterol causes atherosclerosis ?
 It gets deposited in the blood vessel and causes
plaque ( thickening) formation.

17.  Which cholesterol is bad?
 LDL cholesterol is bad. Why?
 because it carries cholesterol from liver to tissues and
excess gets deposited in the blood vessels of tissues
such as heart, brain, kidney, nerves, peripheral
tissues.
 What are the complications?
 Causing nephropathy, neuropathy, retinopathy,
coronary artery disease, cerebral atherosclerosis,
peripheral arterial disease.

18.  Which cholesterol is good?
 HDL cholesterol is good since it transports
cholesterol from tissues to liver for excretion.
 How to increase HDL?
 Exercise improves HDL cholesterol.
 How to proceed further in this case?
 Revise antidiabetic treatment
 Add statin drug if not started

19. Case 5
 A 35 year old male came to skin OPD for the complaint
of yellowish plaques over eyelids. No pain. No other
lesions.

20.  Xanthelasma palpebrarum was suspected and the
following investigations were done.
 Physical examination- Height: 164 cm, weight: 66 kg,
body mass index (BMI): 25.15 kg/m2. Blood pressure
of 126/85 mmHg. Heart rate- 87 /min,
 Not anemic, not jaundiced, no pedal edema

21. Complete blood count
Hb – 14.2 g/dl ( 13.5 – 16 g/dl)
RBC - 4. 6 ( 4-6 millions /micro l)
WBC – 8600 (4500 – 11000 / micro l)
Platelet - 220000 ( 150000 – 450000 per
micro l)

22. Lipid profile
 Serum total cholesterol – 225 mg/dl (140-
200 mg/dl)
 Serum triglycerides – 132 mg/dl ( 50 -150 mg
/dl)
 Serum LDL - 152 mg/dl ( < 100 mg/dl)
 Serum HDL 37 mg/dl ( 40 -60 mg/dl)
 Apo B/ApoA1 ratio - 2.7 ( 0.22- 2.24)

23. Possibilities
Diabetes mellitus
Obstructive jaundice
Renal failure
Hypothyroididsm
Familial hypercholesterolemia

24.  Plasma glucose- Fasting 86 mg/dl ( 70- 100
mg/dl)
 Plasma glucose – Postprandial - 128 mg/dl ( <
140 mg/dl)
 Serum bilirubin- 0.9 mg/dl (<1 mg/dl)
 AST - 36 U/L ( <40 u/L)
 ALT - 32 U/L ( < 40 U/L)
 ALP - 81 U/L ( 40 -150 U/L)

25. Serum urea - 24 mg/dl ( 15-40 mg/dl)
Serum creatinine - 0.9 mg/dl ( 0.6 – 1.2
mg/dl)
Serum uric acid - 5.2 mg/dl ( 4- 7 mg/dl

26. Thyroid function tests
TSH - 2.8 ( 0.2 – 5.0 mIU/l)
T4 - 6.1 (5.0 – 12.0 microg /dl)
T3 - 135( 80- 220 ng/dl)

27. Family history
 History of early heart attacks in his family
among his father and father’s brothers
 Diagnosis
Familial hypercholesterolemia

28.  What is the defect in familial hypercholesterolemia ?
 Familial hypercholesterolemia is an Autosomal
dominant genetic disorder. It is caused by a defect
on chromosome 19.
 LDL receptor deficiency results in the accumulation of
LDL cholesterol leading to rapid progression of
atherosclerotic process.
 What are the complications?
 Early heart attacks, stroke, Gangrene

29. Case 6
 A 57 years old male complained of severe chest pain radiating to the
left arm, sweating, shortness of breath for two hours.
 He was immediately shifted to the emergency dept.
 He was taken emergency ECG and blood investigations.
 ECG findings
 ST segment elevation in the inferior leads (II, III and aVF)
 Reciprocal ST segment depression in the lateral and/or high lateral
(I, aVL, V5 and V6)
 Suggestive of myocardial infarction

30. Three types of heart attacks
ST segment elevation myocardial infarction
(STEMI)
non-ST segment elevation myocardial
infarction (NSTEMI)
coronary spasm, or unstable angina.

31. ECG changes in MI

32. ST elevation and Depression

33. Blood investigations
 Plasma glucose (Random) - 280 mg/dl
 Blood urea – 22 mg/dl ( 15-40 mg/dl)
 Troponin I – 5.2 ( < 0.04 ng/ml)
 Troponin T - 6.5 ( < 0.04 ng/ml)
 Creatine kinase MB( CK-MB)- 27 ( < 5 ng/ml)
 Serum total cholesterol – 217 mg/dl (140-200
mg/dl)
 Serum triglycerides – 165 mg/dl ( 50 -150 mg /dl)
 Serum LDL - 145 mg/dl ( < 100 mg/dl)
 Serum HDL 42 mg/dl ( 45 -60 mg/dl

34. Troponin T , I and CK-MB elevated
ECG changes
Typical chest pain
Diagnosis
Myocardial infarction

35. Case 7
 A 1-year-old boy was referred to hospital due to
abdominal distention and poor weight gain.
 He was the first male offspring of consanguineous
parents.
 He had neurodevelopmental delay,
hepatosplenomegaly, severe hypotonia, difficulty in
breathing.
 Ophthalmological examination revealed the presence
of cherry-red spot in the macula.

36. Histochemistry of a dried blood spot for
the acid sphingomyelinase level -
11 nmol/L per 24 h (normal value: 200–
2500 nmol/L per 24 h)
Diagnosis- Niemann-Pick disease
Deficiency in acid sphingomyelinase, a
lysosomal enzyme.
It results in an accumulation of
sphingomyelin in lysosomes

37. It leads to cellular apoptosis and there
will be hepatosplenomegaly,
neurodegenerative disorder and
failure to thrive.
It has poor prognosis
There is no specific treatment

38. Thank you