Disorders of Lipid 
Metabolism
Dr. Amar Babikir Elhussein 
Associate Professor of Biochemistry and Molecular Biology
Disorders of Lipid Metabolism
?Importance in clinical medicine.ketones
o Features: muscle weakness, cardiomyopathy
o Hypoketotic hypoglycemia
o Tx: carnitine, avoid fasting
MCAD Deficiency
o Defect: medium-chain acyl-CoA dehydrogenase
o Biochemical: block in ?-oxidation
o Features: hypoketotic hypoglycemia, seizures
o Risk of sudden infant death
o Tx: avoid fasting, IV glucose
Other FA Oxidation Defects
o VLCAD deficiency (long-chain)
o CPT I/II deficiency (carnitine shuttle)
o Features: impaired fasting tolerance
o Myopathy, weakness
Ketone Body Disorder: HMG-CoA Lyase Deficiency
o Defect: HMG-CoA lyase
o Biochemical: cannot make ketones
o Features: fasting hypoglycemia, seizures
o Labs: absent ketones
o Tx: frequent feeding, glucose
Ketone Body Utilization: SCOT Deficiency
o Defect: SCOT enzyme
o Biochemical: cannot utilize ketones
o Features: ketoacidosis, neurologic crises
o Tx: avoid fasting, supportive
Succinyl-CoA:3-ketoacid CoA transferase
Gaucher Disease
o Defect: ?-glucocerebrosidase
o Biochemical: glucocerebroside accumulation
o Features: hepatosplenomegaly, bone crises
o Crumpled paper macrophages
o Tx: enzyme replacement
Niemann-Pick Disease
o Defect: sphingomyelinase
o Biochemical: sphingomyelin accumulation
o Features: cherry-red macula, hepatosplenomegaly
o Neurodegeneration
Tay-Sachs Disease
o Defect: hexosaminidase A
o Biochemical: GM2 ganglioside accumulation
o Features: cherry-red macula, neurodegeneration
o No hepatosplenomegaly
Fabry Disease
o Defect: ?-galactosidase A (X-linked)
o Biochemical: Gb3 accumulation
o Features: angiokeratomas, neuropathic pain
o Renal failure
o Tx: enzyme replacement
Summary & Take-Home Messages
o Disorders grouped by defect
o Key = enzyme/protein deficiency
o Labs + clinical signs -> diagnosis
o Therapy: diet, drugs, enzyme replacement
o Clinical importance: CAD, pancreatitis, organ failurecholesterol
o Tx: diet, fibrates, omega-3
Abetalipoproteinemia
o Defect: MTP mutation -> no ApoB lipoproteins
o Biochemical: no chylomicrons, VLDL, LDL
o Features: fat malabsorption, vitamin deficiency
o Labs: absent ApoB lipoproteins
o Tx: vitamins, diet
*Gene encodes the microsomal triglyceride transfer 
protein (MTP)
Tangier Disease (Hypoalphalipoproteinemia)
o Defect: ABCA1 mutation
o Biochemical: impaired cholesterol efflux -> low HDL
o Features: orange tonsils, neuropathy
o Labs: HDL  severe risk
o Therapeutic target = ?Key Clinical Consequences
o Dyslipidemia -> atherosclerosis, CAD
o TG excess -> pancreatitis
o FA oxidation defects -> hypoglycemia
o Lysosomal defects -> organomegaly, neurodegeneration
Classification of Disorders
o Hyperlipoproteinemias (I-V)
o Hypolipoproteinemias
o FA oxidation defects
o Ketone body disorders
o Lysosomal storage diseases
Type I: Familial Chylomicronemia
o Defect: LPL or ApoC-II deficiency
o Biochemical: TG not hydrolyzed
o Features: eruptive xanthomas, pancreatitis
o Labs: ?TG, milky plasma
o Tx: very-low-fat diet
Type IIa: Familial 
Hypercholesterolemia
o Defect: LDL receptor/ApoB mutation
o Biochemical: impaired LDL clearance
o Features: tendon xanthomas, arcus cornealis
o Labs: ?LDL
Visual Summary (Hypolipoproteinemias)
o ApoB deficiency -> absent LDL/chylomicrons
o ABCA1 defect -> absent HDL
o LCAT defect -> abnormal HDL
o Lab patterns & signs compared
Carnitine Deficiency
o Defect: impaired FA transport
o Biochemical: ?Identify hyper/hypolipoproteinemias
?Recognize FA oxidation & ketone body disorders
?Correlate defect with clinical outcome
Normal Lipid Transport (Overview)
o Chylomicrons: dietary TG transport.LDL + VLDL
o Tx: statins +- fibrates
Type III: Familial Dysbetalipoproteinemia
o Defect: ApoE2 homozygous
o Biochemical: ??Focus: lipoproteins, FA oxidation, storage diseases.