The Spectrum of Movement Disorders in Childhood‐onset Lysosomal Storage Diseases

Abstract

Movement disorders develop in a significant number of LSD patients. Ataxia, often in patients with NPC and NCL, is the most common phenotype but significant heterogeneity exists within and between different LSD.

Movement Disorders in Treatable Inborn Errors of Metabolism

“…In all IEMs that present with acute dystonic attacks, acute worsening, including presentations with life‐threatening status dystonicus, is possible; thus, timely recognition and treatment is warranted. Other diseases that tend to present in the first decade of life include GLUT‐1 deficiency syndrome, an important treatable condition, and storage disorders that often present with gradual onset of symptoms such as different forms of neurodegeneration with brain iron accumulation (NBIA), congenital disorders of autophagy, and lysosomal storage diseases (Supporting Information Table S1).…”

“…Juvenile parkinsonism as a consequence of mutations in the Parkin , PINK1‐ , or DJ1 genes presents with parkinsonism as the leading movement disorder and predominates in the clinical course. IEMs that more commonly present with parkinsonism include the neurotransmitter diseases,,Wilson's disease, and other, more‐rare metal storage diseases such as the manganese transporter defects, lysosomal storage diseases such GM2‐gangliosidosis, lipid storage diseases such as cerebrotendinous xanthomatosis, some of the NBIA syndromes, particularly pantothenat‐kinase–associated neurodegeneration and beta‐propeller–associated neurodegeneration, as well as a number of different mitochondrial disorders (Supporting Information Table S1).…”

“…Myoclonus is found in IEM that present with neurodegeneration and cortical myoclonus is most common. Neurodegenerative IEMs that present with myoclonus include lysosomal storage diseases, such as the neuronal ceroid lipofuscinoses, and metal storage diseases such as Wilson's diseases. Mitochondrial cytopathies, such as mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes or myoclonic epilepsy with ragged red fibers, commonly present with myoclonus .…”

“…Broadly speaking, there are two neurological presentations defined by the age of onset and severity: (1) an early‐onset and often quickly progressive form with significant developmental delay starting in infancy or childhood, followed by cerebellar dysfunction with ataxia and dysarthria, spasticity, dystonia, vertical supranuclear gaze palsy, gelastic cataplexy, seizures, and cognitive decline; (2) a delayed form with onset in adolescence or adulthood with intellectual disability, ataxia, vertical supranuclear gaze palsy, and psychiatric symptoms. Movement disorders are common across the spectrum of NPC and sometimes a presenting symptom, particularly in adult patients . The classic movement disorder is that of cerebellar ataxia with prominent involvement of the trunk and limbs, which is present in >70% of patients .…”

“…Hence, NPC should be considered in all patients with onset of ataxia before the age of 40 years and particularly when present in combination with abnormal vertical saccades, cognitive decline, or neuropsychiatric symptoms . Dystonia is a second important movement disorder in NPC, occurring in up to 40% of patients, and can present initially as dystonic tremor of the head and neck and often progresses to generalized dystonia . Facial involvement, particularly of perioral muscles, is common.…”