Krabbe Disease in the Arab World

Abstract

The autosomal recessive inherited Krabbe disease (KD) is a devastating pediatric lysosomal storage disorder affecting white matter of the brain. It is caused by mutations in the gene coding for the lysosomal enzyme galactocerebrosidase. While most patients present with symptoms within the first 6 months of life, others present later in life throughout adulthood. The early infantile form of KD (EIKD) is frequent in the Muslim Arab population in Israel, with a very high prevalence of approximately 1/100 to 1/150 live births. The homozygous variant c.1582G > A (p.D528N) was found to be responsible for EIKD in Palestinian Arab patients. KD was reported in different Arab countries with much lower frequency. While most Arab patients presented with EIKD, late infantile and late onset KD forms were also reported. Most Arab patients presented with variable symptoms ranging from EIKD to late onset KD, with variable clinical findings. Based on literature studies, this review focuses on the clinical and molecular findings of KD patients with Arab ancestry, and highlights the need for developing universal genetic screening programs to overcome the under-reported status of KD prevalence in Arabia. This is expected to improve the prognosis of the disease and promote targeted molecular diagnostics to the Arab patients.

Ethnic disparity in Israel impacts long-term results after heart transplantation

“…Both Ashkenazi and Sephardic Jews have been knowingly segregated for generations, and as such have diseases typically attributed almost solely to these separate populations (Tay-Sachs, Canavan) [9, 10]. Israeli Arabs are also known for their segregation and consanguinity and accordingly show an increase prevalence of certain diseases (Thalasemia major, Krabbe) [11, 12].…”

A neglected neurodegenerative disease: Adult-onset globoid cell leukodystrophy

“…An increasing number of pathogenic gene mutations has been reported in the past three decades ( Wenger et al, 2021 ). Until now, a total of 296 GALC gene mutations related to GLD have been cataloged in the Human Gene Mutation Database (HGMD), including missense mutations, non-sense mutations, deletion, and insertion ( Figure 1 ), and the sites and types of gene mutations have regional and racial variation ( Rafi et al, 1996 ; Kleijer et al, 1997 ; Xu et al, 2006 ; Zayed, 2015 ). Unlike infantile GLD with mutations in the central domain of the coding region, adult GLD has GALC mutations at the N or C terminals, and most mutations are located in GALC gene region encoding 50-kDa subunits ( Furuya et al, 1997 ; Wenger et al, 1997 ).…”

Krabbe Disease: Prospects of Finding a Cure Using AAV Gene Therapy

“…Multiple epidemiological studies have been conducted on KD but the data has been difficult to reconcile due to the use of different study populations and varying methods of estimation ( 14 ). The accepted incidence of KD in Europe is 1:100,000 ( 15 , 16 ) and in some communities with consanguineous marriages like the Druze and Muslim Arabs, the incidence of KD is estimated at 1:100 to 1:150 ( 17 ). Although previous studies suggest an estimated incidence of 1:250,000 in the USA ( 18 ), an epidemiological study done in New York state (NYS) using newborn screening data estimated the state-wide incidence to be 1:394,000 ( 19 ).…”