Uncommon Allies: Van der Knaap Syndrome and Focal Segmental Glomerulosclerosis.

Abstract

Background: Van der Knaap disease, or megalencephalic leukoencephalopathy with subcortical cysts (MLC), is a rare autosomal recessive leukodystrophy caused by mutations in the MLC1 or GLIALCAM genes. It is characterized by macrocephaly, developmental delays, ataxia, spasticity, seizures, progressive neurodegeneration, and subcortical cysts, particularly in individuals from consanguineous populations.

Objective: To report a unique case of a 26-year-old male with MLC who developed steroid-resistant focal segmental glomerulosclerosis (FSGS), an association not previously described. The study aims to highlight potential links between neurodegenerative and renal pathologies and underline the importance of multidisciplinary care.

Materials and methods: The diagnosis of MLC was based on clinical presentation, magnetic resonance imaging (MRI) findings, and genetic testing that confirmed an MLC1 mutation. The patient's FSGS was resistant to standard steroid therapy, necessitating immunosuppressive treatment, including rituximab. A review of the literature was conducted to explore possible connections between the two conditions.

Results: The patient exhibited hallmark features of MLC and developed concurrent FSGS. Management involved targeted immunosuppressive therapies, leading to partial control of symptoms. The cooccurrence of these conditions, though rare, suggests a potential shared genetic or mechanistic pathway, which remains to be elucidated.

Conclusion: This case illustrates the complex interplay between neurodegenerative and renal disorders, emphasizing the need for multidisciplinary management. The rare association of MLC and FSGS raises questions about potential genetic links or shared molecular mechanisms, warranting further research to identify targeted therapies.