Pannuzzo, G, Graziano, ACE, Avola, R, Drago, F, Cardile, V. Screening for Krabbe disease: The first 2 years’ experience. Acta Neurol Scand . 2019; 00: 1– 7.
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Globoid cell leukodystrophy or Krabbe disease (KD) is a lysosomal storage disorder characterized by a deficiency in galactosylceramidase (GALC) which breaks down (hydrolyses) galactosylceramide and galactosylsphingosine (psychosine). The accumulation of psychosine results in the death of myelin-forming cells.
KD is inherited in an autosomal recessive inheritance pattern. Carriers of autosomal recessive disorders are called heterozygotes and typically show no symptoms of leukodystrophy; however, they are at an increased risk of having a child with KD. We all have 2 copies of each gene. Carriers “carry” one good copy of the gene (non-affected copy) and one disease-causing gene. When two (2) carriers have children together, with each pregnancy, there is a 1 in 4 (25%) chance the child will not be affected by the disorder, a 1 in 2 (50%) chance the child will also be a carrier, and a 1 in 4 (25%) chance the child will be affected with KD.
This is a bit easier to show by using what we call a Punnett Square. The Aa on the top represents the father and the Aa on the left of the square represents the mother. The capital A represents the good gene or unaffected gene and the lower- case a represents the disease-causing gene. In the lower-right hand square, you can see by combining the lower-case a (affected gene) of the father and the lower-case a, the affected gene of the mother, there is a 1 in 4 chance of the child being affected with Krabbe disease.
So, now that we understand the inheritance pattern of KD, let’s learn about the goals and findings of this research study.
- This study looked to identify the heterozygous carriers of Krabbe disease in Sicily (Italy), to prevent the birth of unborn babies affected by Krabbe disease, and eventually in the presence of positive results for KD, direct them towards a treatment before symptoms occur when it is too late to receive a useful therapy.
- Due to the high incidence of the late infantile form in Sicily, the authors think that it could be very significant to realize a statistic and systematic study to know the real incidence of KD in this region and to identify the heterozygous carriers of the disease.
- There are notable practical benefit to families that have had a child with Krabbe disease and researchers who deal with this rare pathology.
- The results of this study will be useful to know the real incidence of Krabbe disease in a large Italian territory where KD is particularly present and to start a Krabbe’s register, which at present does not exist.
Results & Key Points
- The study began with the screening of relatives of patients, whose gene variant (often called mutation) was known.
- It’s important to remember that screening tests are not considered diagnostic. The primary purpose of screening tests is to detect potential health disorders in people who do not have any symptoms.
- The choice and accuracy of the testing method provided a fast, easy and painless test and defined the target population to be screened.
- In the last 2 years, the analysis of almost 100 individuals in the Italian region found 40 heterozygous carriers of Krabbe disease. One of the women examined was pregnant.
- Carrier detection by molecular genetic testing is possible if the disease-causing variants have been identified in the family.
- Prenatal diagnosis can be performed either by measurement of GALC enzyme activity or by molecular genetic testing if both pathogenic genes (alleles) in an affected family member are known.