Hemorrhagic shock and encephalopathy syndrome in a patient with a de novo heterozygous variant in KIF1A

Introduction: KIF1A, a gene that encodes a neuron-specific motor protein, plays important roles in cargo transport along neurites. Variants in KIF1A have been described in three different disorders, and neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment syndrome (NESCAVS) is the severest phenotype. Case report: A 3-year-old girl was born at term with a birth weight of 2590 g. At five months of age, she visited our hospital due to developmental delay. An EEG showed multiple epileptic discharge, and a nerve conduction study showed severe axonopathy of both motor and sensory nerves. We performed exome sequencing and identified a de novo heterozygous missense variant in KIF1A (NM_001244008.1: c. 757G > A, p.E253K). At six months of age, she developed acute encephalopathy, multiple organ failure and disseminated intravascular coagulation, necessitating intensive care. Her brain CT showed severe brain edema, followed by profound brain atrophy. We diagnosed hemorrhagic shock and encephalopathy syndrome (HSES) according to the clinico-radiological features. Currently, she is bed-ridden, and requires gastrostomy because of dysphagia. Conclusion: The clinical course of our case confirmed that p.E253K is associated with severe neurological features. Severe KIF1A deficiency could cause thermoregulatory dysfunction and may increase the risk of acute encephalopathy including HSES.