Hyperkinetic movement disorders in congenital disorders of glycosylation

Abstract

Background and purpose Congenital disorders of glycosylation (CDG) represent an increasing number of rare inherited metabolic diseases associated with abnormal glycan metabolism and disease onset in infancy or early childhood. Most CDG are multisystemic diseases mainly affecting the central nervous system. The aim of the current study was to investigate hyperkinetic movement disorders in patients affected by CDG and to characterize phenomenology based on CDG subtypes. Methods Subjects were identified from a cohort of patients with CDG who were referred to the University Hospital of Catania, Italy. Patients were evaluated by neurologists with expertise in movement disorders and videotaped using a standardized protocol. Results A variety of hyperkinetic movement disorders was detected in eight unrelated CDG patients. Involuntary movements were generally observed early in childhood, maintaining a clinical stability over time. Distribution ranged from a generalized, especially in younger subjects, to a segmental/multifocal involvement. In patients with phosphomannomutase 2 CDG, the principal movement disorders included dystonia and choreo‐athetosis. In patients affected by other CDG types, the movement disorders ranged from pure generalized chorea to mixed movement disorders including dystonia and complex stereotypies. Conclusions Hyperkinetic movement disorder is a key clinical feature in patients with CDG. CDG should be considered in the differential diagnosis of childhood‐onset dyskinesia, especially when associated with ataxia, developmental delay, intellectual disability, autism or seizure disorder.

Movement Disorders and Renal Diseases

“…160,161 Cerebellar ataxia and other movement disorders may be part of the complex phenotype of several hereditary disorders that involve the nervous system and other visceral organs including, rarely, the kidneys, such as congenital disorders of glycosylation and peroxisomal disorders. [162][163][164] The discussion of all of these disorders is beyond the scope of this review. Disclosures Ethical Compliance Statement: Approval from institutional review board or ethics committee was not required for this work.…”

Epilepsy and movement disorders in CDG: Report on the oldest‐known MOGS‐CDG patient

“…Furthermore, dystonic hand movements were reported also in another patient with PMM2‐CDG (Neumann et al, 2003). In addition, stereotypical dystonic hand movements were described in a 17‐month‐old girl with CDG‐x (later diagnosed with SRD5A3‐CDG; Prietsch et al, 2002; Jaeken et al, 2020), and “abnormal movements” are mentioned in MGAT2‐CDG (Mostile et al, 2019).…”

“…CDG phenotypes are heterogeneous, and usually characterized by multi‐organ involvement including neurological features such as psychomotor disability, hypotonia, ataxia, epilepsy, stroke‐like episodes, and peripheral neuropathy (Fiumara et al, 2016). Dystonia and hyperkinetic movement disorders have only sporadically been described in CDG patients (Mostile et al, 2019).…”

A Proposed Diagnostic Algorithm for Inborn Errors of Metabolism Presenting With Movements Disorders

“…Quite apart from the fact that many of these report do not provide in-depth characterization of the MD. Some studies that include large series of patients with IEMs and MD are: Tetrahydrobiopterin (BH4) deficiencies (37), cobalamin-related remethylation disorders (38), SERAC1 deficiency (39), mitochondrial disorders (22), PLA2G6associated neurodegeneration (24), lysosomal storage disorders (40), cerebrotendinous xanthomatosis (9), and congenital disorders of glycosylation (41). IEMs with MD as a primary or prominent feature and treatable causes should always be in mind.…”