Hkp

In 1949, Watson et al. described hereditary coproporphyria = HKP for the first time (Lang 2014).

Due to the sometimes very different clinical appearance, acute porphyria was described by Waldenström in 1937 as a "small imitator", in contrast to syphilis, which he described as a "large imitator" (Gerischer 2021).

The term HKP refers to hereditary coproporphyria. This corresponds to one of the four forms of acute hepatic porphyria:

- Acute intermittent porphyria (AIP )

- Hereditary coproporphyria (HKP)

- Porphyria variegata (PV)

- Delta-aminolevulinic acid dehydrogenase-deficient porphyria (Doss porphyria). (Herold 2018)

HKP is widespread worldwide. Women are affected more frequently than men. HKP is a very rare disease, with < 50 cases described. (Lang 2014).

In 2018, Plewig already speaks of around 200 documented cases.

HKP is a hereditary disease in which there is a defect in the enzyme coproporphyrinogen oxidase (CPOX) (Lang 2014). Inheritance is autosomal dominant (Gerok 2007).

Porphyrias comprise a group of genetic diseases with partly autosomal dominant and partly autosomal recessive inheritance. They are caused by an enzyme deficiency in heme biosynthesis (Gerischer 2021).

The disease is latent before puberty and usually only becomes manifest during puberty (Kasper 2015).

Both homozygous and heterozygous mutations are associated with the clinical picture (Lang 2014).

The disease progresses in episodes. These are often associated with the use of certain medications, changes in the female reproductive organs or a calorie deficiency (Wang 2022). There are primarily neurovisceral symptoms in the form of:

- Mild abdominal pain at the beginning, increasing to severe colicky or crampy abdominal pain within days (Wang 2022)

- tachycardia

- vomiting

- nausea

- Constipation or diarrhea

- Hypertension

- Hypernatremia

- muscle weakness

- Respiratory paralysis

- fever

- Increased sweating

- hypesthesia

- paraesthesia

- Paralysis symptoms such as para- and tetraplegia

- anxiety

- Confusion

- delirium

- insomnia

- depression

- Hallucinations

- Psychoses (Lang 2014)

The neuropathic symptoms also show increasing severity over the course of days. If a seizure remains untreated, motor neuropathy can develop within days or weeks (Lang 2014).

Skin changes have also been described in around a third of those affected (Gerok 2007), consisting of:

- increased vulnerability of the skin

- blisters, blisters, erosions, crusts, milia, scars, hypo- or hyperpigmentation form on light-exposed areas

- occasionally actinic elastosis and hypertrichosis in the facial area (Lang 2014)

The acute attacks and skin changes are identical to those of porphyria variegata (Lang 2014).

In an acute attack, the diagnosis can be made using a biochemical screening test. This detects a significant increase in porphobilinogen in the urine (Wang 2022).

In order to differentiate between the various forms of porphyrias and to be able to make a diagnosis of HKP, stool tests are essential (Wang 2022). Elevated porphyrins are detected in the stool (Kasper 2015). Protoporphyrin is usually only slightly elevated and coproporphyrin is significantly elevated (Lang 2014).

In the acute phase, the urine contains an increase in:

- Aminolevulinic acid (ALA)

- porphobilinogen (PBG)

In the remission phase, both values are back within the normal range (Lang 2014).

In the stool, however, both in the acute phase and in the remission phase, there is an increase in:

- Protoporphyrin (slightly elevated)

- Coproporphyrin (significantly increased) (Lang 2014)

- Acute intermittent porphyria (AIP )

- Porphyria variegata (PV)

- Porphyria cutanea tarda

- Delta ALA dehydratase deficiency porphyria (Lang 2014)

The treatment of HKP corresponds to that of porphyria variegata (Lang 2014). s. d.

Affected patients should avoid fasting and taking certain medications such as phenytoin and barbiturates, and women should also avoid oral contraceptives and progesterone (Wang 2022).

In patients with chronically elevated ALA levels and / or > 60 years of age, kidney and liver values should be checked once a year, as well as screening for hepatocellular carcinoma and determination of alpha-fetoprotein in patients > 60 years of age (Wang 2022).

1. Gerischer L M, Scheibe F, Nümann A, Köhnlein M, Stötzel U, Meisel A (2021) Acute porphyrias - A neurological perspective. Brain Behav. 11 (11) e2389 doi: 10.1002/brb3.2389. Epub 2021 Oct 17
2. Gerok W, Huber C, Meinertz T, Zeidler H (2007) Internal medicine: reference work for the specialist. Schattauer Publishers Stuttgart / New York 1153, 1161
3. Herold G et al. (2018) Internal medicine. Herold publishing house 702
4. Kasper D L, Fauci A S, Hauser S L, Longo D L, Jameson J L, Loscalzo J et al. (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 2531
5. Lang E (2014) Studies on the development of benign and malignant tumors in patients with acute hepatic porphyria. Dissertation for the degree of Doctor of Medicine of the Medical Faculty of Heinrich Heine University Düsseldorf
6. Plewig G, Kaufmann R, Ruzicka T, Hertl M (2018) Braun- Falco's Dermatology, Venereology and Allergology. Springer Verlag GmbH Germany 1705
7. Wang B, Bissell D M, Adam M P, Feldman J, Mirzaa G M, Pagon R A, Wallace S E, Bean L JH, Gripp K W, Amemiya A (2022) Hereditary Coproporphyria. GeneReviews Seattle , University of Washington. PMID: 23236641, Bookshelf ID: NBK114807 doi: https://pubmed.ncbi.nlm.nih.gov/23236641/