Hypolipoproteinemia

Lipid Disorders Main Page
Overview
Causes
Classification Abetalipoproteinemia Hypobetalipoproteinemia Familial hypoalphalipoproteinemia LCAT Deficiency Chylomicron retention disease Tangier disease Familial combined hypolipidemia
Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]; Aravind Kuchkuntla, M.B.B.S[3]; Tarek Nafee, M.D. [4]

Synonyms and keywords: Hypolipidemia, low lipoprotein

Overview

Hypolipoproteinemia is defined as low levels of one or more type of lipoproteins. Hypolipidemia, a commonly used term in the clinical practice, describes low level of lipids, whether cholesterol or triglycerides. They are referred to as hypocholesterolemia and hypotriglyceridemia respectively. Despite being commonly used to describe abnormalities in lipid metabolism, the term hypolipidemia is not very specific. For instance, people who have metabolic syndrome have high LDL and low HDL and yet they are described to have hyperlipidemia when their HDL level is decreased. Moreover, some people who have low levels of a specific lipoprotein may have a normal measured total cholesterol and triglyceride levels.

Synopsis

• It is defined as patients having LDL C less than the 5th percentile when compared to normal population.
• We have to rule out secondary causes first and then consider screening for rare genetic diseases.

	Abetalipoprotienemia	Familial Homozygous Hypobetalipoproteinemia	Familial Heterozygous Hypobetalipoproteinemia	PCSK9 deficiency	Chylomicron Retention Disease	Familial Combined Hypolipidemia
LDL C	↓↓↓ (0)	↓↓↓	↓	↓	↓↓	↓↓
Apo B	↓↓↓( 0)	↓↓↓	↓	N	↓↓	N
TG	↓↓↓	↓↓↓	↓	↓	N	↓
TC	↓↓↓	↓↓↓	↓	↓	↓↓	↓
HDL	↓↓	↓↓	N	N	↓↓	↓↓
VLDL	↓↓	↓↓	↓	N	↓↓	↓
Apo A1	↓↓	↓↓	↓	N	↓↓	N

Classification

Shown below is an algorithm depicting the classification of hypolipoproteinemia into primary and secondary.

Hypolipoproteinemia

Primary (Genetic)

Secondary

Abetalipoproteinemia Apolipoprotein 1 deficiency Chylomicron retention disease Familial combined hypolipidemia Hypobetalipoproteinemia LCAT deficiency Primary alphalipoproteinemia PCSK9 deficiency Tangier disease

Anemia Criticial illness Chronic inflammation Chronic liver disease Hyperthyroidism Infection Malabsorption Malignancy

Diagnostic Approach to Hypolipoproteinemias

Low LDL Diagnostic Algorithm

The following Algorithm may be used to diagnose patients with low LDL hypolipoproteinemias:

Low LDL C <5th percentile

Rule out secondary causes of low LDL

Lipid panel

Normal Triglycerides

Low Triglycerides

Chlyomicron retention disease (Confirm with gene sequencing)

Screen the lipid panel of the patient's parents

Normal Parental Lipid Panel

If Parental Lipid Panel <50% of Normal on: *LDL *Total Cholesterol *Triglycerides

Hypobetalipoproteinemia (Confirm with gene sequencing)

Abetalipoproteinemia (Confirm with gene sequencing)

Low HDL Diagnostic Features

	Familial LCAT Deficiency	Fish Eye Disease	Homozygous Tangier Disease	Heterozygous Tangier Disease
Gene Defect	LCAT	LCAT	ABCA1	ABCA1
Inheritance	Autosomal Recessive	Autosomal Recessive	Autosomal Recessive	Autosomal Recessive
Pathogenesis	Loss of alpha and beta LCAT function Failure of cholesterol ester formation.	Loss of alpha function only	Pre beta-1 HDL fails to picks up free cholesterol from cells due to mutation in ABCA1 transporter.	Similar to homozygous
Clinical Features	Annular corneal opacity Anaemia Progressive renal disease with proteinuria	Corneal opacities only Normal renal function	Large yellow-orange tonsils Dense central corneal opacity relapsing and remitting course of neuropathy	Asymptomatic
Lipid Panel	Elevated Free cholesterol HDL-C < 10 mg/dL Low Apo A1 and Apo A2 Elevated Apo E and Triglycerides Low LDL C	Elevated free cholesterol HDL C < 27 mg/dL Apo A1＜30mg/dl and low Apo A2 Elevated Apo E and Triglycerides Normal LDL and VLDL	HDL < 5% of normal Apo A1 < 1% of normal LDL < 40% of normal	HDL C, Apo A1 and LDL 50% less than normal.
2D Gel Electrophoresis	Pre β-1 and α-4 HDL, LDL with β mobility due to Lipoprotien-X	Pre β-1and α-4 HDL with normal pre-β LDL.	Only preβ-1 HDL present	Lack of large α-1 and α-2 HDL particles Normal preβ-1 HDL