Clinical Guidance

In CETP-related HALP, the degree of elevation of HDL-C is related to the amount of residual CETP activity. Homozygosity for the common canonical splice site variant (known as the Intron 14 A variant), is associated with higher HDL-C levels . In contrast, missense pathogenic variants such as (known as the D442G variant) is associated with modest effects on CETP activity (37%-62% of normal in homozygotes) and milder effects on HDL-C levels .

Source: GeneReviews — "CETP-Related Hyperalphalipoproteinemia"

Diagnostic Criteria

No consensus clinical diagnostic criteria for CETP-related hyperalphalipoproteinemia (HALP) have been published.

Suggestive Findings

Biallelic (homozygous or compound heterozygous) CETP-related HALP should be suspected in probands with moderate hypercholesterolemia, markedly increased high-density lipoprotein cholesterol (HDL-C), and low low-density lipoprotein cholesterol (LDL-C), consistent with the following:

• Plasma total cholesterol level of 220-320 mg/dL (5.7-8.3 mmol/L)

• HDL-C level of 100-250 mg/dL (2.6-6.5 mmol/L)

• LDL-C level of 30-130 mg/dL (0.8-3.4 mmol/L)

• Apolipoprotein (apo) A-I level of 150-280 mg/dL (1.5-2.8 g/L)

• Apo B level of 30-80 mg/dL (0.3-0.8 g/L)

Heterozygous CETP-related HALP should be suspected in probands with a moderate increase in HDL-C, consistent with the following:

Source: GeneReviews — "CETP-Related Hyperalphalipoproteinemia"

Differential Diagnosis

Other genes associated with primary hyperalphalipoproteinemia (HALP) are listed in . Table 2. Genes of Interest in the Differential Diagnosis of CETP-Related Hyperalphalipoproteinemia

Management Guidelines

No clinical practice guidelines for CETP-related hyperalphalipoproteinemia (HALP) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of findings in an individual diagnosed with CETP-related HALP, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

CETP-Related Hyperalphalipoproteinemia: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Cardiovascular

| Obtain plasma lipid profile incl:

• Total cholesterol

• HDL-C

• LDL-C

• Triglycerides

• Apo A-I

• Apo B

|

Noninvasive imaging of carotid plaque burden by duplex ultrasonography | Consider referral to cardiologist.

Coronary calcium score /or CT coronary angiography to assess for coronary atherosclerosis

Genetic counseling

| By genetics professionals1 | To obtain a pedigree inform affected persons their families re nature, MOI, implications of CETP-related HALP to facilitate medical personal decision making

apo = apolipoprotein; HALP = hyperalphalipoproteinemia; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; MOI = mode of inheritance

1. Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)

Treatment of Manifestations

Source: GeneReviews — "CETP-Related Hyperalphalipoproteinemia"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "CETP-Related Hyperalphalipoproteinemia"

Surveillance Guidelines

To monitor affected individuals, the evaluations summarized in are recommended.

Table 5.

CETP-Related Hyperalphalipoproteinemia: Recommended Surveillance

System/Concern | Evaluation | Frequency

Cardiovascular

| Cardiovascular risk assessment, incl noninvasive assessment of atherosclerotic plaque burden | As clinically indicated

Source: GeneReviews — "CETP-Related Hyperalphalipoproteinemia"