Table 2.

Characteristics of inborn errors of metabolism and mitochondrial cytopathies where chorea is the predominant movement disorder.

Type of Metabolic Disorder	Conditions; Gene	Region; Age	Inheritance Pattern	Mov Disord	Key Findings	Seizures	Ataxia	Pyramidal signs	DD	Other Sx	I and L	Tx
Organic acidemias	Glutaric aciduria type 1; GCDH	Neonatal	AR	Choreo-athetosis Dystonia Orofacial dyskinesia	Macrocephaly Acute encephalopatic crisis Opisthotonus	Yes	No	No	Yes	No	L: urinary glutaric acid, 3-hydroxyglutaric acid, glutaconic acid.	Low lysine diet and oral carnitine supplementation
	Propionic acidemia; PCCA and PCCB	Amish, Inuit of Greenland and Saudi Arabian populations; Neonatal or infancy	AR	Choreoathetosis	Poor feeding Lethargy Encephalopathy Vomiting Hypotonia	Yes	No	Yes	Yes	Hepatomegaly Failure to thrive Optic atrophy Hearing loss Premature ovarian failure Chronic renal failure Cardiomyopathy Attention-deficit disorder Autism	L: Plasma amino acids, acylcarnitines, and urinary organic acids, and orotic acid. I: Lesions in the bilateral lenticular and caudate nuclei	Protein-restricted diet; Treat metabolic acidosis, hypoglycemia, hyperammonemia
	Methylmalonic acidemia; MUT	First year	AR	Choreoathetosis Dystonia	Encephalopathy Stroke Hypotonia Lethargy Monilial infections	Yes	No	No	Yes	Dysphagia Dysarthria Failure to thrive Hepatosplenomegaly	L: Elevated blood and urine levels of ammonia, glycine, methylmalonic acid, propionic acid. I: Bilateral globus pallidus lesions	Protein-restricted diet, cyanocobalamin, and levo-carnitine supplementation
	OPA3-related 3-methylglutaconic aciduria (Costeff syndrome); OPA3	Iraqi-Jewish descent; Before age ten years	AR	Choreoathetosis	Optic atrophy Spastic paraparesis	No	Yes	No	No	No	L: Urinary excretion of 3-methylglutaconic acid	Supportive
Amino acid metabolism	Nonketotic hyperglycinemia; GLDC or AMT	Neonatal, infancy, adulthood	AR	Chorea	Lethargy, coma Hypotonia, hiccups Myoclonic jerks	Yes	No	Yes	Yes	Breathing/swallowing disorders	I: Elevated glycine levels in CSF and plasma.	Sodium benzoate Dextromethorphan Seizure management
	Homocystinuria; CBS MTHFR, MTR, MTRR, MMADHC	1st or 2nd decade	AR	Chorea Dystonia	Ectopia lentis, severe myopia Thromboembolism Skeletal and skin abnormalities	Yes	No	No	Yes	No	L: Increased serum levels of homocysteine and methionine	Vitamin B6 Methionine-restricted diet Folate Vitamin B12 Betaine
Purine metabolism	Lesch-Nyhan disease; HPRT1	3 to 6 mo.	X-linked	Choreoathetosis Dystonia	Self-injurious behavior Gouty arthritis Crystals or calculi in kidneys, ureters, bladder	No	No	Yes	Yes	Hypotonia Behavioral disturbances	L: Urinary urine-to-creatine ratio greater than 2.0 Hyperuricemia Hyperuricuria	Allopurinol Symptomatic
Creatine metabolism	Cerebral creatine deficiency syndrome 2 (GAMT deficiency); GAMT	Early infancy to 3 yrs.	AR	Choreoathetosis Dystonia	Hyperactivity, autism, self-injurious behavior	Yes	Yes	No	No	No	I: Hyperintensities in basal ganglia	Creatine monohydrate supplementation Ornithine supplementation Protein- or arginine-restricted diet
Glucose transport	GLUT1 deficiency; SLC2A1	Infancy	AD; AR	Chorea Dystonia	Paroxysmal episodes of mov disord or epilepsy Atypical childhood absence epilepsy Myoclonic astatic epilepsy	Yes	Yes	No	Yes	Microcephaly	L: Low CSF:serum glucose ratio	Ketogenic diet Symptomatic
Lipid storage	Niemann Pick Type C; NPC1 or NPC2	Infancy, children, adults	AR	HD phenocopy in adult onset Dystonia	Vertical supranuclear gaze palsy Dementia	Yes	Yes	No	Yes	Hypotonia Liver disease Respiratory failure	I: cerebellar atrophy or periventricular hyperintensities	Symptomatic
Other	Sulfite oxidase deficiency; SUOX	Infancy	AR	Choreoathetosis Dystonia	Ectopia lentis Eczema Failure to thrive	Yes	Yes	No	Yes	Hypotonia	L: Increase sulfite levels in urine I: Calcification of basal ganglia and cerebellar hypoplasia	Low sulfur amino acid diet Low protein diet
Mitochondrial cytopathies	Leigh syndrome and Leigh-like syndromes; MT-ND, MTATP6	First mo. to yrs. of life	X-linked, AR	Choreoathetosis Dystonia Parkinsonism	Ophthalmologic abnormalities Cardiac, hepatic, gastrointestinal and renal symptoms.	No	Yes	No	Yes	Hypotonia	L: Increased blood lactate levels. I: T2-weighted hyperintensities in basal ganglia and brainstem.	Biotin, thiamine, Coenzyme Q10 supplements
	Pyruvate carboxylase deficiency; PC	First yr.	AR	Choreoathetosis Tremors	Microcephaly Disconjugate eye movements, poor pupillary response, blindness, poor visual tracking Respiratory abnormalities	Yes	Yes	Yes	Yes	Hypotonia	L: Elevated blood levels of ammonia, pyruvate, lactate, acetoacetate and beta-hydroxybutyrate. I: periventricular WM cysts, subcortical FP hypernintensities.	Cofactor supplementation with thiamine and lipoic acid and administration of dichloroacetate
	Pyruvate dehydrogenase complex deficiency; PDHA1	Infancy	X-linked	Choreoathetosis Dystonia	Poor feeding Lethargy Tachypnea Abnormal eye movements Dysmorphic features Respiratory abnormalities	Yes	Yes	Yes	Yes	Microcephaly Hypotonia	L: Elevated blood levels of lactate and pyruvate I: absence of corpus callosum and medullary pyramids, ectopic inferior olives, symmetric cystic lesions and gliosis, generalized hypomyelination.	Cofactor supplementation with thiamine, carnitine, and lipoic acid.

Mov Dis: Movement Disorders; Sx: Symptoms; DD: Developmental delay; I: Imaging; L: Laboratory; AR: Autosomal recessive; AD: Autosomal dominant; CSF: cerebrospinal fluid; WM: white matter; FP: frontoparietal.

* Only the disorders of metabolism where chorea is the predominant movement disorder are included.

* Wilson’s disease is described under autosomal recessive hereditary choreas.