Approaches To Dyslipidemia
Treatment in Children and
Adolescents
Lorenzo Iughetti; Barbara Predieri;
Patrizia Bruzzi; Fiorella Balli
Table 1. Major Genetic Disorders of Lipid Metabolism
Genetic primary
disorder
Genetic defect
Clinical features
FH
LDL-R, dimished LDL-C clearance
Heterozygotes: xanthomas on the extensor tendons of the hands and feet,
arcus corneae and premature CVD; TC: 250-500 mg/dL (LDL-C>135
mg/dL)
Homozygotes: xanthomas and very premature CVD; TC: 500-1000 mg/dL
Other autosomal
dominant
hypercholesterolemia
PCSK9, diminished LDL-C clearance
Heterozygotes: xanthomas on the extensor tendons of the hands and feet,
arcus corneae and premature CVD; TC: 250-500 mg/dl (LDL-C>135
mg/dl)
Homozygotes: xanthomas and very premature CVD; TC:500-1000mg/dl
ARH
ARH adaptor protein absent or unable
to interact with the LDL-R, diminished
LDL-C clearance
Variable, phenotype similar to homozygous FH, but generally less severe
and more responsive to lipid-lowering therapy; large and bulky xanthomas
from early childhood; TC>500 mg/dl
Familial defective
ApoB-100
ApoB-100, diminished LDL-C
clearance
Xanthomas, arcus senilis and premature CVD; TC: 250-500 mg/dl
Polygenic
hypercholesterolemia
Unknown, multiple defects and
mechanisms
Premature CVD; TC: 250-350 mg/dl
Familial
hyperchylomicronemia
Unknown, possible multiple defects
and mechanism
TG: 500-1000 mg/dl (occasionally >1000 mg/dl with dietary factors and
alcohol); TC high, LDL-C and HDL-C low; frequent episodes of abdominal
pain with or without recurrent attacks of acute pancreatites,
hepatosplenomegaly, lipemia retinals and eruptive xanthomas; variable
Apo-CII deficiency
Apo-CII (causing functional complete
or partial LPL deficiency)
Pancreatites, often associated with metabolic syndrome;
hepatosplenomegaly; TG>750 mg/dl; chylomicrons markedly elevated,
LDL-C and HDL-C low
Familial combined
hyperlipidemia
Unknown
Premature CVD, ApoB elevated; TC: 250-500 mg/dl; TG: 250-750mg/dl
Dysbetalipoproteinemia
ApoE, impaired chylomicron and
VLDL-C clearance
Tuberous and tuberoeruptive xanthomas; premature CVD or peripheral
vascular disease; abnormal glucose tolerance; TC: 250-500 mg/dl;
TG:250-750 mg/dl; VLDL-C markedly increased, LDL-C reduced
Hypoalphalipoproteine
mia
Unknown
Variable, premature CVD; HDL-C: 15-35 mg/dl
Apo = Apolipoprotein; ARH = Autosomal recessive hypercholesterolemia; C = Cholesterol; CVD = Cardiovascular disease; FH = Familial hypercholesterolemia; HDL = High-density lipoprotein; LDL
= Low-density lipoprotein; TC = Total cholesterol; TG = Triglyceride; VLDL = Very-low-density lipoprotein.
Table 2. Secondary Disorders of
Lipid Metabolism
Secondary Disorder
Clinical Feature
Obesity
Increased TG, decreased HDL-C
Diabetes mellitus
Increased TG and TC, decreasedHDL-C
Chronic renal failure
Increased TG and TC, decreasedHDL-C
HIV/AIDS wasting
Increased TG and TC, decreasedHDL-C
and LDL-C
HIV/AIDS (HAART)
Increased TG, TC and HDL-C
Hypothyroidism
Increased TG, TC and LDL-C
Nephrotic syndrome
Increased TC and LDL-C
Obstructive liver disease
Increased TC
Medications
Variable
C = Cholesterol; HAART = Highly-active antiretroviral therapy; HDL = High-density lipoprotein; LDL =Low-density
lipoprotein; TC = Total cholesterol; TG = Triglyceride.
Table 3. Characteristics and Differences
Between STEP 1, STEP 2 and TLC Diets
Diet
Total fats
(% of total
calories)
Saturated
fats (% of
total
calories)
Dietary
cholesterol
(mg/day)
Plants
stanols/ster
ols (g/day)
Increased
viscous
soluble
fiber (g/day)
STEP 1
30
No more
than 10
Limited to
300
NA
NA
Step 2
30
Less than 7
Less than
200
NA
NA
TLC
25-35*
Less than 7
Less than
200
2
10-25
*The 25-35% fat recommendation allows for increased intake of unsaturated fat in place of carbohydrates in people with
metabolic syndrome or diabetes.
NA = Not applicable; TLC = Therapeutic Lifestyle Changes.
From National Cholesterol Education Program ATP III
Table 4. Studies With Bile Acid-binding Resins
in Children With Familial Hypercholesterolemia
Drug and dosage (g/day)
Author
Subjects (n)
Age
(years)
Follow-up
Study
Mean LDL-C
reduction (%)
Ref
0.5-0.6 g/kg
Mordasini etal. (1978)
20
7-15
16 weeks
RCT
-25.0
[115]
8-20 g
Glueck etal. (1986)
33
5.5-18
5.6 years
RCT
-12.5 (total
cholesterol)
[67]
5-30 g
Stein (1989)
30
1-20
1-9 years
Open
-21.0
[116]
0.125-0.25 g/kg
Schlierf etal. (1982)
26
3-24
8 weeks
RCT
-12.0 to -15.0
[117]
10-15 g
Groot etal. (1983)
24
7-15
16 weeks
RCT
-15.7
[118]
10 g
Tonstad etal. (1996)
66
10-16
1 year
RCT
-19.5
[68]
2-12 g
Tonstad etal. (1996)
27
10-16
24 weeks
Open
-20.0
[69]
12-16 g
Glueck etal. (1977)
16
9-17
3 years
Open
-14.0
[119]
4-8 g
Wets etal. (1980)
35
1.3-17.4
8 years
Open
-26.0 to -44.0
(totalcholesterol)
[120]
0.36 g/kg
Koletzko etal. (1992)
14
2.3-17.8
4-97 months
RCT
-13.5
[121]
8-24 g
Liacouras etal. (1993)
36
6-15
1-2.5 years
Open
-26.0
[122]
8g
Tonstad (1996)
96
6-11
1 year
RCT
-16.9 to -18.6
[71]
8g
McCrindle (1997)
38
10-18
16 weeks
RCT
-10.0 to -15.0
[70]
8g
Hussein (2001)
16
10-18
16 weeks
RCT
-14.0
[72]
Asami (2002)
6
4-16
24 weeks
RCT
-34.0
[73]
Colestipol or cholestyramine
Colestipol
Cholestyramine
Colestilan
4g
LDL-C = Low-density lipoprotein cholesterol; RCT = Randomized controlled trial.
Table 5. Studies With Statins in Children With
Familial Hypercholesterolemia
Drug and dosage
(mg/day)
Author
Subjects (n)
(M/F)
Age (years)
Follow-up
Study
Mean LDL-C
reduction (%)
Ref.
5-40
Ducobu et al. (1992)
32 (22/10)
<17
2-3 years
Open
-37.3
[78]
20
Couture et al. (1998)
63 (37/26)
8-17
6 weeks
RCT
-31.0 to -38.0
[123]
10
Stefanutti et al. (1999)
16 (7/9)
4-12
52 weeks
RCT
-29.0
[79]
10-40
de Jongh et al. (2002)
173 (98/75)
10-17
48 weeks
RCT
-40.7
[80]
20
Vohl et al. (2002)
47 (28/19)
8-17
6 weeks
Open
-31.0 to -39.0
[84]
5-20
Dirisamer et al. (2003)
20 (8/12)
10-17
52 weeks
Open
-25.0 to -36.0
[81]
10
Ferreira et al. (2007)
18 (10/8)
6-18
4 weeks
RCT
-37 %
[83]
5-20
Knipscheer et al. (1996)
72 (25/47)
8.0-16.0
12 weeks
RCT
-23.3 to -32.9
[85]
10
Hedman et al. (2003)
20 (7/13)
4.9-15.6
8 weeks
Open
-21.0
[89]
20-40
Wiegman et al. (2004)
214 (100/114)
8.0-18.5
2 years
RCT
-24.1
[86]
10-60
Hedman et al. (2005)
30 (11/19)
4.1-18.5
2 years
Open
-24.5 to -32.0
[47]
20-40
Rodenburg et al. (2007)
186 (91/95)
8-18.5
4.5 years
RCT
- 29.2
[87]
20
Sinzinger (1992)
13 (8/5)
6-13
4 years
Open
-28.0 to -54.0
[124]
10-40
Lambert et al. (1996)
69 (69/0)
9.3-17.5
8 weeks
RCT
-21.0 to -36.0
[92]
10-40
Stein et al. (1999)
132 (132/0)
10-17
48 weeks
RCT
-17.0 to -27.0
[93]
40
Kwiterovich et al.(2001)
132 (132/0)
10-17
3-7 years
RCT
-27
[94]
20-40
Clauss et al. (2005)
54 (0/54)
10-17
24 weeks
RCT
-23 to - 27
[95]
10-40
Athyros (2002)
16 (16/0)
10-17
156 weeks
Open
-45.0
[96]
10-20
McCrindle et al. (2003)
187 (129/58)
10-17
26 weeks
RCT
-39.6
[97]
Van der Graaf (2006)
84 (37/47)
10-16
2 years
Open
-33.9
[99]
Simvastatin
Pravastatin
Lovastatin
Atorvastatin
Fluvastatin
80
F = Female; LDL-C = Low-density lipoprotein cholesterol; M = Male; RCT = Randomized controlled trial.