Neurodevelopmental delay, corneal clouding, hypomyelinating leukoencephalopathy: think mucolipidosis IV
Mane Tadevosyan 1,*, Biayna Sukhudyan 1,2, Davit Babikyan 3, Eugen Boltshauser 4
1 Department of Pediatric Neurology, Arabkir Medical Complex, Yerevan, Armenia
2 Department of Neurology and Neurosurgery, Avdalbekyan National Institute of Health, Yerevan, Armenia
3 Center of medical genetics and primary health care, Yerevan, Armenia
4 Department of Pediatric Neurology, University Children’s Hospital, Zurich, Switzerland
* Corresponding author: Email: mane9511@gmail.com
Abstract
Mucolipidosis type IV (MLIV) is an ultra-rare autosomal recessive lysosomal disorder characterized by typical neurological (early-onset developmental delay, spasticity), ocular (corneal clouding, retinopathy), and characteristic MRI findings (hypomyelinating leukoencephalopathy, thin corpus callosum, cerebellar atrophy). Although MLIV is predominantly reported in patients in the Ashkenazi Jewish community, it is a pan-ethnic disorder. The authors report on two siblings of Armenian origin with global neurodevelopmental delay, ophthalmological abnormalities and characteristic MRI features suggesting MLIV. Whole-Exome Sequencing confirmed two pathogenic variants in the MCOLN1 gene. This constellation of clinical and neuroimaging findings has been confirmed to provide a basis for the diagnosis of MLIV, and it is suggested that a focused diagnostic work-up should be considered for unexplained neurodevelopmental disorders.
Keywords: Mucolipidosis IV, MCOLN1, corneal clouding, hypomyelination, cerebral palsy