Late infantile metachromatic leukodystrophy in a palestinian girl: Report of a vovel mutation in ARSA gene

Background: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by mutations in ARSA gene resulting in a deficiency of the enzyme arylsulfatase A (ASA). The late-infantile variant of MLD is the most frequent and severe phenotype. The aim of the study is to report a novel mutation in ARSA further expanding the genotype of this disorder Methods: Case study of a 30-month old Palestinian girl who presented with the typical phenotype of late-infantile MLD (psychomotor regression, progressive quadraparesis, ataxia, dysphagia, weakness with areflexia). Brain magnetic resonance imaging (MRI) showed the characteristic pattern. Genomic amplification of the whole ARSA gene exons and direct sequencing was performed on DNA extracted from peripheral blood sample Results: T2-weighted MR image demonstrates bilateral confluent areas of high signal intensity in the periventricular white matter with posterior predominance and sparing of the subcortical U fibers. Genomic amplification of the whole ARSA gene exons and direct sequencing performed on DNA extracted from peripheral blood sample showed that the patient is homozygous for the novel mutation R86G (p.Arg86Gly, c.256 C > G) in exon 2 and homozygous for the mutation T393C in exon 7 of ARSA gene. R86G mutation is a novel mutation detected for the first time in MLD patients. However, several other disease causing mutations such as R86W and R86Q were documented at the same codon. T393C mutation has been found to have a mild functional effect. Family segregation analysis confirmed that both parents and two siblings were heterozygous for the two mutations and the other two siblings were normal J Inherit Metab Dis (2016) 39 (Suppl 1):S35–S284 S271 Discusssion: Since cloning of ARSA cDNA and gene, More than 150 mutations have been reported. Our report further expands the genetic spectrum of late- infantile MLD