analyt molecular genetics English

Porphyria, acute intermittend (HMBS)

OMIM: 176000
Diagnostic method:

Sequencing and CNV: HMBS

Samples required:

2 ml EDTA blood

Duration of analysis: 4-6 weeks
Forms:  

Acute intermittent porphyria (AIP) is inherited autosomal dominant and is the most common form of acute porphyria. AIP is characterised by acute (intermittent) neurological disorders in which attacks of porphyria alternate with pain-free phases. Women are affected more frequently than men. The peak of the disease lies in the third decade of life.

The extent of the symptoms of AIP is very variable. Many patients have no symptoms or are latently ill. Only about 20 % of the carriers are affected by clinical manifestations of AIP in the course of their lives.

Acute porphyria attacks are often drug-induced, but can also be triggered by infections, alcohol, surgery, stress, diet and hypoglycaemia. In episodes, classic neurological symptoms such as colicky, severe abdominal pain, which can be accompanied by constipation, nausea and vomiting, tachycardia, arterial hypertension (high blood pressure), muscle weakness, paralysis, psychosis, cerebral seizures, paraesthesia and paresis can be observed.

Symptoms of acute intermittent porphyria
(with decreasing frequency)
stomach pains
tachycardia
peripheral paralysis
paraesthesias
vomiting
constipation
diarrhoea
muscle weakness
cramps
respiratory paralysis
mental symptoms (confusion, hallucinations)
letterpress
epileptic seizures
coma

In the case of an acute attack, the patients often receive intensive medical care, as neurovisceral complaints (e. g. acute abdomen) and neurological deficits often occur, which can be fatal. Patients with an AIP must therefore be provided with emergency cards and informed in detail about their illness and the factors that can trigger attacks. By avoiding these “triggers”, acute, life-threatening neurological attacks can be prevented or at least alleviated.

Therapeutically, during an acute attack, the administration of glucose, which inhibits d-ALA synthase, or haeme-arginate (normosang), is the main therapy. The supply of heme inhibits the first enzyme of heme synthesis and thus the formation of porphobilinogen (PBG). Pain, severe vomiting, tachycardia requiring therapy or hypertension are treated symptomatically. Laboratory controls are recommended to accompany the therapy.

The AIP is caused by mutations in the hydroxymethyl balance synthase gene (HMBS gene), which is mapped on the long arm of chromosome 11 (11q23.3) and encodes the protein porphobilinogen desaminase (PBGD). PBGD is the third enzyme of haeme biosynthesis. In the presence of a mutation in the HMBS gene, the activity of PBGD is reduced by approximately 50 %, which is sufficient for porphyrin synthesis under normal metabolic conditions. Acute attacks of porphyria occur when haeme synthesis is increased by drugs, alcohol or infections and the lack of PBGD activity leads to the accumulation of porphyrin precursors. This accumulation causes the above symptoms.

A rapid and reliable diagnosis is therefore of utmost importance in order to be able to initiate adequate therapy and to limit neurological damage.

Indication:

  • accumulation of porphyrins and porphyrin precursors (D-ALA, PBG) in urine
  • acute onset, colic-like abdominal pain
  • muscle weakness of unknown cause
  • unclear neurological disorders
  • familial accumulation

 

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