[P1-176] Metachromatic Leukodystrophy: A Single Center Experience in Saudi Arabia
[Introduction] Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder resulting from Arylsulfatase-A (ARSA) or rarely Saposin-B deficiency that leads to the accumulation of sulfatides and subsequent demyelination of the nervous system. We set to examine the clinical, diagnostic, genetic data, therapeutic interventions and outcome in our MLD population.
[Methodology] We conducted a retrospective analysis of MLD patient records who were diagnosed at our institution between January 2002 and December 2014.
[Results] Thirty-three patients were diagnosed with MLD (58% males) including 20 (60%) with late-infantile and 13 (40%) with juvenile form. Median age at onset was 19 (range 15-30) months for late-infantile and 57 (36-108) months for juvenile group. Mean follow-up duration was 3.1 years (1 month-8.6 years). Most patients (80%) presented with motor regression. Seizures were evident in 40% of patients and responded well to therapy. Periventricular demyelination (78%) and corpus callosum involvement (70%) were the most common findings on brain MRI. Saposin-B deficiency accounted for 33% of cases. Three novel ARSA gene mutations were identified. Of the Saposin-B mutations, 7/8 (88%) originated from a founder gene (c.722G>C) and 1/8 identified as novel (c.441G>C) mutation. Sixteen patients (48%) underwent bone marrow transplantation (BMT) and one patient underwent ARSA gene therapy. Four of the treated (25%) and 6 of the untreated patients (35%) expired during follow-up (p=0.4).
[Conclusions] Saudi MLD patients have an unexpectedly high rate of Saposin-B deficiency with most mutations originating from a founder gene. BMT appears to provide no improved survival in our relatively small cohort of MLD population.
[Methodology] We conducted a retrospective analysis of MLD patient records who were diagnosed at our institution between January 2002 and December 2014.
[Results] Thirty-three patients were diagnosed with MLD (58% males) including 20 (60%) with late-infantile and 13 (40%) with juvenile form. Median age at onset was 19 (range 15-30) months for late-infantile and 57 (36-108) months for juvenile group. Mean follow-up duration was 3.1 years (1 month-8.6 years). Most patients (80%) presented with motor regression. Seizures were evident in 40% of patients and responded well to therapy. Periventricular demyelination (78%) and corpus callosum involvement (70%) were the most common findings on brain MRI. Saposin-B deficiency accounted for 33% of cases. Three novel ARSA gene mutations were identified. Of the Saposin-B mutations, 7/8 (88%) originated from a founder gene (c.722G>C) and 1/8 identified as novel (c.441G>C) mutation. Sixteen patients (48%) underwent bone marrow transplantation (BMT) and one patient underwent ARSA gene therapy. Four of the treated (25%) and 6 of the untreated patients (35%) expired during follow-up (p=0.4).
[Conclusions] Saudi MLD patients have an unexpectedly high rate of Saposin-B deficiency with most mutations originating from a founder gene. BMT appears to provide no improved survival in our relatively small cohort of MLD population.