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  • Test code: 06159
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Hereditary Fructose Intolerance Test

Test description

The Invitae Hereditary Fructose Intolerance Test analzyses the ALDOB gene. Pathogenic variants in ALDOB lead to hereditary fructose intolerance (HFI), which is caused by a deficiency of the enzyme fructose 1-phosphate aldolase (aldolase B) in the liver and kidneys.

This test is indicated for any individual in whom hereditary fructose intolerance is suspected based on clinical or laboratory findings. Early diagnosis is important for proper management of clinical symptoms. Identification of disease-causing variants provide accurate risk assessment and carrier status for at-risk relatives.

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Primary panel (1 gene)
  • hereditary fructose intolerance (HFI)

Hereditary fructose intolerance (HFI) is a metabolic disorder characterized by a deficiency of activity of the enzyme fructose 1-phosphate aldolase (aldolase B) in the liver and kidneys. Those affected with HFI typically come to clinical attention when they react to the introduction of fructose, sucrose, or sorbitol into their diets during the weaning process in infancy. Ingestion of these sugars results in acute symptoms including vomiting, nausea, abdominal pain, and sweating, as well as hypoglycemia and metabolic acidosis. Continued exposure to harmful sugars in infancy and childhood can result in growth restriction, failure to thrive, renal and hepatic injury, and even death. However, when properly diagnosed the condition responds dramatically to a to a diet restricting fructose,sucrose and/or sorbitol, except for hepatomegaly. For affected individuals with proper dietary restrictions, prognosis is excellent.

Pathogenic sequence variants and deletion/duplication events in the ALDOB gene are identified in up to 100% of individuals affected with hereditary fructose intolerance in some populations. In some areas of the world full gene analysis is not typically offered (due to the high cost), and thus efforts have been made to identify and offer testing for common mutations in certain ethnic populations; this limited testing may account for some reports of lower clinical sensitivity (PMID: 23430936, 25595217, 26677512).

Hereditary fructose intolerance is inherited in an autosomal recessive manner.

Available data is limited, however the prevalence of hereditary fructose intolerance is estimated to be between 1 in 18,000 and 1 in 60,000 individuals.

This test may be appropriate for individuals who have any of the following after introduction of fructose, sucrose, or sorbitol into their diets:

  • metabolic disturbances
    • hypoglycemia
    • lactic acidemia
    • hypophosphatemia
    • hyperuricemia
    • hypermagnesemia
    • hyperalaninemia
  • clinical findings
    • vomiting, nausea, abdominal pain, and sweating
    • growth restriction
    • failure to thrive

  1. Ali, M, et al. Hereditary fructose intolerance. J. Med. Genet. 1998; 35(5):353-65. PMID: 9610797
  2. Ali, M, et al. Null alleles of the aldolase B gene in patients with hereditary fructose intolerance. J. Med. Genet. 1994; 31(6):499-503. PMID: 8071980
  3. Ananth, N, et al. Two cases of hereditary fructose intolerance. Indian J Clin Biochem. 2003; 18(2):87-92. PMID: 23105397
  4. Choi, HW, et al. A Novel Frameshift Mutation of the ALDOB Gene in a Korean Girl Presenting with Recurrent Hepatitis Diagnosed as Hereditary Fructose Intolerance. Gut Liver. 2012; 6(1):126-8. PMID: 22375183
  5. James, CL, et al. Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population. J. Med. Genet. 1996; 33(10):837-41. PMID: 8933337
  6. Santer, R, et al. The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe. Hum. Mutat. 2005; 25(6):594. PMID: 15880727
  7. Gruchota, J, et al. Aldolase B mutations and prevalence of hereditary fructose intolerance in a Polish population. Mol. Genet. Metab. 2006; 87(4):376-8. PMID: 16406649
  8. Lazarin, GA, et al. An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. Genet. Med. 2013; 15(3):178-86. PMID: 22975760
  9. Ferri, L, et al. Integration of PCR-Sequencing Analysis with Multiplex Ligation-Dependent Probe Amplification for Diagnosis of Hereditary Fructose Intolerance. JIMD Rep. 2012; 6:31-7. PMID: 23430936
  10. Bijarnia-Mahay, S, et al. Molecular Diagnosis of Hereditary Fructose Intolerance: Founder Mutation in a Community from India. JIMD Rep. 2015; 19:85-93. PMID: 25595217
  11. Baker, P, et al. Hereditary Fructose Intolerance. 2015 Dec 17. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 26677512
  12. Steinmann B, Santer R. Inborn metabolic diseases: diagnosis and treatment. 5th ed. Heidelberg: Springer; 2012. Chapter 9, Disorders of fructose metabolism; p. 157-165.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ALDOB NM_000035.3