Metabolic movement disorders comprehensive panel [32 genes]
Inherited metabolic disorders are a group of diseases that include defects affecting enzymes or proteins involved in cellular metabolism. Many of these diseases have neurological manifestations and can present with complex clinical pictures, combining cognitive and muscular symptoms, ataxia, epilepsy, and movement disorders.
Most commonly, movement disorders are not so much a predominant symptom as one of the manifestations of the disease. However, some metabolic disorders can start with some type of abnormal involuntary movement as their first symptom. Particularly, dystonia, myoclonus, chorea, stereotypies, and parkinsonism may be part of this spectrum of manifestations. The importance of these diseases lies in the fact that many of them can be effectively treated and that their early identification can prevent neurological damage.
In a cohort of patients with movement disorders studied by Gouider-Khouja et al. (2010), up to 29% were found to have a movement disorder secondary to metabolic disease, with dystonia and myoclonus as the most frequent symptoms (54% and 28%, respectively).
- One of the metabolic disease groups with the highest overall prevalence of movement disorders are mitochondrial diseases. Suspicion of any of these diseases should lead to the study of the mitochondrial genome or of nuclear genes involved in mitochondrial metabolism (see specific panel).
- On the other hand, we have selected some phenotypes that should be included in the differential clinical diagnosis due to the occurrence of a movement disorder as the first symptom.
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- ARSA: Metachromatic leukodystrophy
- ATP7B: Wilson’s disease
- CP: Aceruloplasminemia/systemic hemosiderosis
- CLN3, CLN5, CLN6, CLN8, CTSD, CTSF, DNAJC5, GRN, MFSD8, PPT1, TPP1: Neuronal ceroid lipofuscinosis
- CYP27A1: Cerebrotendinous xanthomatosis
- FOLR1: Cerebral folate transport deficiencyl
- GBA: Gaucher disease
- GALC: Krabbe disease
- GCDH / L2HGDH: Glutaric aciduria type 1 and L-2-hydroxyglutaric aciduria
- GLB1, GM2A, HEXA, HEXB: Gangliosidosis
- NPC1, NPC2, SMPD1: Niemann-Pick disease type C and types A & B
- PTS, QDPR: Tetrahydrobiopterin deficiency/Hyperphenylalaninemia
- SLC19A3, SLC25A19, TPK1: Thiamin and biotin-responsive encephalopathies
- Gouider-Khouja N, Kraoua I, Benrhouma H, Fraj N, Rouissi A. Movement disorders in neuro-metabolic diseases. Eur J Paediatr Neurol. 2010 Jul;14(4):304-7.