Co-occurrence of Phelan-McDermid syndrome and metachromatic leukodystrophy
DOI:
https://doi.org/10.18203/issn.2454-2156.IntJSciRep20250059Keywords:
Phelan-McDermid syndrome, Metachromatic leukodystrophy, SHANK3, Arylsulfatase AAbstract
Very few cases have been described so far with co-occurrence of Phelan-McDermid syndrome (PMS) and metachromatic leukodystrophy (MLD). Those patients harbour a chromosome (chr) 22q13deletion encompassing at least the SHANK3 and ARSA genes and a pathogenic variant in the arylsulfatase A (ARSA) gene residing on the other allele. The deletion in chr22q13 results in PMS phenotype and the presence of pathogenic variation on the other intact copy of ARSA gene, leads to MLD phenotype due to biallelic loss of ARSA function. We describe a male infant, born to a third-degree consanguineous couple, who exhibited neuroregression at the age of 8 months, presented with developmental delay, hypotonia which rapidly progressed to feeding difficulties, axial hypotonia, ptosis, sleep disturbance, dystonia, spasticity, and abnormal eye movements. Brain MRI showed T2 hyperintensities consistent with MLD. Biochemical workup showed deficiency of ARSA enzyme activity. Genetic investigations revealed heterozygous deletion of size 2.5 Mb on chr 22q13.3 encompassing the entire ARSA gene and a pathogenic variant in the other copy of ARSA gene. Parents and sibling were tested and informed about the disease management and genetic testing in extended family members to understand the risk and preventive measures. Few case reports have proposed screening for urine sulfatides levels at the time of PMS diagnosis to identify pre-symptomatic or asymptomatic MLD patients to facilitate management and our case supports this proposal.
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References
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