Diagnosis of metachromatic leukodystrophy in a patient with regression and Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a 22q13.3 deletion syndrome. Most PMS patients show global developmental delay and some of them suffer from developmental regression. The deleted region contains ARSA, which is responsible for metachromatic leukodystrophy (MLD). Here we report an extremely rare case of PMS characterized by unusual, rapidly progressive developmental regression due to additional pathogenic mutation in ARSA. Considering the 1 in 100 chance of an MLD carrier, co-occurrence of PMS and MLD in a patient is possible if either parent carries a heterozygous ARSA mutation. Therefore, MLD should be ruled out in PMS patients with severe neurological phenotype.