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For patients

Molecular Genetics

All congenital GPI-anchor deficiencies represent rare disorders. About one in 10,000 newborn is affected by a GPI-anchor deficiency. Cases have been reported from all over the world and it seems to be a disorder that occurs in all ethnicities. GPI-anchor deficiencies are a recessive disorder, that means parents of affected individuals are unaffected and only carry the genetic defect. If the same genetic sequence variant has been observed in several affected individuals and functional analysis prove that the variant impairs the GPI-anchor synthesis, then this sequence variant is also referred to as a pathogenic mutation. Medical Genetics may help to identify the cause of a disorder and may help to assess how the future cause of the disorder will be. When the causal genetic variant is known, predictive genetic tests can be performed during pregnancy.

Besides congenital GPI-anchor deficiencies, there are also acquired GPI-anchor defects. In contrast to congenital mutations, acquired mutations are more severe and the impairment only affects certain cells in the body. The acquired GPI-anchor deficiency that affects cells of the blood system is called paroxysmal nocturnal hemoglobinuria, PNH, and about 1 in a 100,000 adults is affected by this disease in his or her life time.


Clinical Features

Individuals with a congenital GPI-anchor deficiency are intellectually disabled. Many of them have epilepsies, that have to be treated. Individuals with Mabry syndrome, a deficiency of the late anchor synthesis and maturation, have an elevated serum activity of the alkaline phosphatase (hyperphosphatasia). The high value of this lab paramter is not import for the clinical management of the patient, however the elevated alkaline phosphatase can be helpful in finding the right diagnosis. Individuals with Mabry syndrome often resemble each other without being related. Characteristic features are a broad nasal bridge and tip of the nose, a large distance between the pupils of the eyes, a small upper lip, and a large head. The nails and distal bones of the fingers and toes are often shortened. 

In individuals with acquired GPI-anchor deficiencies only blood cells are affected. If red blood cells do completely lack GPI-anchors, then also proteins are missing on the surface that protect these cells from the own immune system. From time to time the red blood cells are attacked by the immune system and hemoglobin is detectable in the urin (paroxysmal nocturnal hemoglobinuria, PNH). Individuals with PNH can be treated with the antibody Eculizumab. We are investigating whether this antibody might also be used to treat congenital GPI-anchor deficiencies.



Diagnostic Process 

In the course of a diagnostic procedure many patients have gone through a clinical Odyssee. German patients are now supported by the Translate NAMSE initiative to facilitate a corrrect diagnosis of this reare disorder. In this sense we launched the PEDIA study where the diseas causing mutation is identified by exome sequencing and with the help of precise description of phenotypic features of the patient and a frontal photo of the patients face. 
PEDIA stands for Prioritization of Exome Data by Image Analysis and is supported by FDNAs platform Face2Gene
You may draw the attention of your clinician to actively participate in the PEDIA study in order to facilitate correct diagnosis of GPI anchor deficiencies and other rare disorders.
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