Clinical Guidance

The majority of APOB pathogenic variants causing biallelic APOB-FHBL and heterozygous APOB-FHBL are frameshift, nonsense and splice variants resulting in production of a truncated apoB protein . These are named as a proportion of full-length wild type protein (apoB-100).

• In general, pathogenic variants that lead to truncated proteins that are 30% in length or shorter have more severe signs and symptoms than those whose truncated protein length is predicted to be 32% or longer; the latter tend to have moderate disease.

• It has been hypothesized that longer apoB truncated proteins may be able to maintain some residual capacity to bind lipid and form lipoproteins .

Source: GeneReviews — "APOB-Related Familial Hypobetalipoproteinemia"

Diagnostic Criteria

In this GeneReview:

Source: GeneReviews — "APOB-Related Familial Hypobetalipoproteinemia"

Differential Diagnosis

Table 4. Genes of Interest in the Differential Diagnosis of Biallelic APOB-Related Familial Hypobetalipoproteinemia

Management Guidelines

No clinical practice guidelines for APOB-related familial hypobetalipoproteinemia (APOB-FHBL) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with or , the evaluations summarized respectively in and (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Biallelic APOB-Related Familial Hypobetalipoproteinemia

Source: GeneReviews — "APOB-Related Familial Hypobetalipoproteinemia"

Clinical Guidance

Individuals with biallelic APOB-FHBL should avoid fatty foods. No dietary restrictions are typically required for those with heterozygous APOB-FHBL.

Source: GeneReviews — "APOB-Related Familial Hypobetalipoproteinemia"

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 — "APOB-Related Familial Hypobetalipoproteinemia"

Surveillance Guidelines

Table 8.

Recommended Surveillance for Individuals with Biallelic APOB-Related Familial Hypobetalipoproteinemia

Frequency | Evaluation

Every 6-12 mos | • Measurement of growth parameters

• For any new or progressive signs/symptoms of gastrointestinal issues1

Every 1-2 yrs | Laboratory investigations:

• Lipid profile2

• Liver function tests3

• Vitamin A, vitamin E, 25-OH vitamin D

• INR

• Calcium, phosphate, uric acid

• CBC measurement of vitamin B12 folate levels4

• TSH5

Every 6-12 mos after age 10 yrs | • Ophthalmology eval

• Neurologic exam

Every 3-5 yrs after age 10 yrs | • Hepatic ultrasound

• Bone mineral densitometry6

CBC = complete blood count; INR = international normalized ratio; TSH = thyroid-stimulating hormone

1. Including for hepatomegaly and diarrhea

2. To include total, LDL and HDL cholesterol, triglyceride, and apo B concentrations

3. To include AST and ALT

4. Abnormal vitamin B12 and folate levels are not a primary feature of biallelic APOB-FHBL. However, the anemia seen in individuals with biallelic APOB-FHBL can mask a vitamin B12 or folate deficiency, both of which can occur with increased frequency in older individuals and both of which are treatable.

5. Abnormal thyroid function is not a primary feature of biallelic APOB-FHBL but is a common co-morbidity in the general population and is also treatable.

6. An affected individual found to have a bone mineral density 1 SD below the lower limit of normal often prompts an increase in vitamin D dosage.

Table 9.

Source: GeneReviews — "APOB-Related Familial Hypobetalipoproteinemia"