Metabolic Stroke as a Clinical Manifestation of Zhu-Tokita-Takenouchi-Kim Syndrome


North Florida


Osceola Regional Medical Center

Document Type

Case Report

Publication Date



Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Neurology


Objective This study reports 2 unrelated individuals with Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome who presented with a metabolic stroke, which has not been commonly reported as a clinical manifestation of this syndrome.

Methods Two female children were identified after presenting to our institution with a metabolic stroke and carried a diagnosis of ZTTK syndrome because of their clinical characteristics and previous genetic testing demonstrating pathogenic variants in SON.

Results Both individuals presented with acute-onset left hemiplegia. They underwent workup, and corresponding metabolic stroke was identified on brain MRI. Both individuals recovered with good functional outcome. One individual was treated with L-arginine, ubiquinol, and levocarnitine. The other individual recovered without any intervention.

Discussion ZTTK syndrome is a rare condition caused by pathogenic variants in SON. This syndrome is characterized by global developmental delay, short stature, facial dysmorphisms, seizures, hypotonia, and brain abnormalities. A metabolic stroke has not been reported as a common manifestation. SON has been reported to play a role in mitochondrial function. This can explain why metabolic stroke can be seen in individuals with ZTTK syndrome. It is important to recognize that metabolic stroke can be a clinical manifestation of ZTTK syndrome because it carries clinical and therapeutic implications.

Publisher or Conference

Neurology Genetics