Card kit

Invitae Acute Hepatic Porphyrias Panel

Test code: 06226 •

Test description

The Invitae Acute Hepatic Porphyrias panel analyzes up to 4 genes (ALAD, CPOX, HMBS and PPOX) associated with the following forms of acute hepatic porphyria: delta aminolevulinic acid dehydratase deficiency porphyria (ADP), hereditary coproporphyria (HCP), acute intermittent porphyria (AIP) and variegate porphyria (VP). This panel may be appropriate for individuals with signs and symptoms of an acute hepatic porphyria with or without cutaneous manifestations. Additionally, this panel may be appropriate for those in whom porphyria is suspected due to abnormal porphyrin excretion. Genetic testing of these genes may confirm a diagnosis, help guide treatment and management decisions, identify at-risk family members, and guide enrollment in clinical trials.

Any individual with significantly increased levels of urinary 5-ALA excretion, with or without increased porphobilinogen, should consider genetic analysis for disease confirmation.

The genes within the Invitae Acute Hepatic Porphyrias panel cannot be combined with any other genes or panels at this time. Please contact Client Services with any questions.

Of note, this panel does not currently include testing for the following types of porphyria:

  • X-linked protoporphyria (XLP) associated with variants in ALAS2
  • Erythropoietic protoporphyria (EPP) associated with variants in FECH
  • Erythropoietic protoporphyria 2 (EPP2) associated with variants in CLPX
  • Porphyria cutanea tarda (PCT) associated with variants in UROD
  • Congenital erythropoietic porphyria (CEP) associated with variants in UROS
  • Hepatoerythropoietic porphyria (HEP) associated with variants in UROD

Disorders tested

GeneDisorder
ALADδ-Aminolevulinic acid dehydratase deficiency porphyria (ADP), also known as Doss porphyria
CPOXHereditary coproporphyria (HCP), also known as coproporphyrinogen deficiency, and harderoporphyria
HMBSAcute intermittent porphyria (AIP), also known as porphobilinogen deaminase deficiency
PPOXVariegate porphyria (VP), also known as protoporphyrinogen oxidase deficiency

Ordering information

Turnaround time:

10–21 calendar days (14 days on average)

New York approved:

Yes

Preferred specimen:

3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)

Alternate specimens:

Saliva, buccal swab, and gDNA are also accepted.Learn more about specimen requirementsRequest a specimen collection kit

Clinical description and sensitivity

Clinical description:

Acute hepatic porphyrias are a group of diverse disorders associated with altered activity of porphyrin enzymes in the heme biosynthetic pathway, which results in accumulation and excess excretion of pathway intermediates and products. Each type of porphyria has characteristic patterns and levels of excess intermediates, which result in different clinical manifestations. For example, the excess porphyrins seen in individuals with hereditary coproporphyria (HCP) and variegate porphyria (VP) have photosensitive effects, causing cutaneous manifestations such as blistering skin lesions, features which are not typically present in individuals with δ-aminolevulinic acid dehydratase deficiency porphyria (ADP) or acute intermittent porphyria (AIP).

Age of onset varies depending on the type of porphyria, inheritance pattern, and certain environmental factors including certain drugs, steroid hormones, and exposure to heavy metals, which may cause previously asymptomatic individuals to display clinical symptoms of porphyria.

Individuals with acute intermittent porphyria (AIP) typically remain clinically asymptomatic throughout life. If clinical symptoms do manifest, onset is typically in adulthood. Individuals present with acute neurovisceral attacks that may last for several days at a time. Symptoms include abdominal pain, cramps, nausea, tachycardia, muscle pain and weakness, tremors, hyponatremia, hypertension, and excess sweating. Peripheral motor neuropathy, characterized by muscle weakness which begins in the proximal upper extremities, may also develop. δ-Aminolevulinic acid dehydratase deficiency porphyria (ADP) is characterized by adolescent-onset attacks of abdominal pain and neuropathy. Exposure to heavy metals such as lead can cause symptoms in heterozygous carriers who would otherwise be asymptomatic. Hereditary coproporphyria (HCP) and variegate porphyria (VP) are characterized by neurovisceral attacks as well as cutaneous manifestations including blistering or non-blistering skin lesions, which are caused by photosensitivity.

First line laboratory testing for individuals displaying acute neurovisceral symptoms includes urinary 5-aminolevulinic acid (5-ALA), porphobilinogen and total porphyrins. All four acute hepatic porphyrias are associated with significant increases in urinary 5-aminolevulinic acid (5-ALA). AIP, HCP, and VP are also associated with increased urinary excretion of porphobilinogen. For individuals with blistering or non-blistering skin lesions, total plasma porphyrins or erythrocyte porphyrins should be tested.

Treatment for the neurological symptoms of acute hepatic porphyrias most commonly consists of intravenous hemin therapy (typically heme arginate) and avoidance of drugs and other environmental factors which are known to be harmful in individuals with acute porphyrias. Cutaneous symptoms are more difficult to treat and center around protection from sunlight exposure. Currently, there is no officially approved treatment available to prevent recurrent attacks.

Clinical description and sensitivity

Clinical description:

Acute hepatic porphyrias are a group of diverse disorders associated with altered activity of porphyrin enzymes in the heme biosynthetic pathway, which results in accumulation and excess excretion of pathway intermediates and products. Each type of porphyria has characteristic patterns and levels of excess intermediates, which result in different clinical manifestations. For example, the excess porphyrins seen in individuals with hereditary coproporphyria (HCP) and variegate porphyria (VP) have photosensitive effects, causing cutaneous manifestations such as blistering skin lesions, features which are not typically present in individuals with δ-aminolevulinic acid dehydratase deficiency porphyria (ADP) or acute intermittent porphyria (AIP).

Age of onset varies depending on the type of porphyria, inheritance pattern, and certain environmental factors including certain drugs, steroid hormones, and exposure to heavy metals, which may cause previously asymptomatic individuals to display clinical symptoms of porphyria.

Individuals with acute intermittent porphyria (AIP) typically remain clinically asymptomatic throughout life. If clinical symptoms do manifest, onset is typically in adulthood. Individuals present with acute neurovisceral attacks that may last for several days at a time. Symptoms include abdominal pain, cramps, nausea, tachycardia, muscle pain and weakness, tremors, hyponatremia, hypertension, and excess sweating. Peripheral motor neuropathy, characterized by muscle weakness which begins in the proximal upper extremities, may also develop. δ-Aminolevulinic acid dehydratase deficiency porphyria (ADP) is characterized by adolescent-onset attacks of abdominal pain and neuropathy. Exposure to heavy metals such as lead can cause symptoms in heterozygous carriers who would otherwise be asymptomatic. Hereditary coproporphyria (HCP) and variegate porphyria (VP) are characterized by neurovisceral attacks as well as cutaneous manifestations including blistering or non-blistering skin lesions, which are caused by photosensitivity.

First line laboratory testing for individuals displaying acute neurovisceral symptoms includes urinary 5-aminolevulinic acid (5-ALA), porphobilinogen and total porphyrins. All four acute hepatic porphyrias are associated with significant increases in urinary 5-aminolevulinic acid (5-ALA). AIP, HCP, and VP are also associated with increased urinary excretion of porphobilinogen. For individuals with blistering or non-blistering skin lesions, total plasma porphyrins or erythrocyte porphyrins should be tested.

Treatment for the neurological symptoms of acute hepatic porphyrias most commonly consists of intravenous hemin therapy (typically heme arginate) and avoidance of drugs and other environmental factors which are known to be harmful in individuals with acute porphyrias. Cutaneous symptoms are more difficult to treat and center around protection from sunlight exposure. Currently, there is no officially approved treatment available to prevent recurrent attacks.


Clinical sensitivity:


Sensitivity by Clinical ConditionGeneClinical Sensitivity Resources
Clinical sensitivity unknown for δ-Aminolevulinic acid dehydratase deficiency porphyria (ADP)ALADN/A
>90% of dominant hereditary coproporphyria (HCP)CPOXPMID: 9888388, 19460837
Clinical sensitivity unknown for recessive harderoporphyriaCPOXN/A
>95% of acute intermittent porphyria (AIP)HMBSPMID: 9199558, 19460837
>95% of variegate porphyria (VP)PPOXPMID: 10486317

Assay 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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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.

Assay 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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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.

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Primary panel

4 genes selected
ALAD
CPOX
HMBS
PPOX

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