Paroxysmal dyskinesias with drowsiness and thalamic lesions in GABA transaminase deficiency

Abstract

The proband (patient 1), a 25-year-old woman, was the product of normal pregnancy and delivery. Her parents were first cousins from Lebanon. She sat at 6 months and crawled at 12 months. At age 3, she was noted to have developmental delay, hypotonia, and ataxia. The following year, she had a febrile illness and suspected absence seizure. EEG showed 4-5 Hz spike and slow wave complexes and she was treated with sodium valproate. At age 6, seizure frequency increased but improved with the addition of ethosuximide. Brain MRI at age 10 revealed increased T2 signal in both thalami and upper brainstem (figure). Serum and urinary amino acids, white blood cell lysosomal enzymes, serum lactate and pyruvate, liver function, and ammonia were normal. CSF neurotransmitters, glucose, and lactate were normal, although GABA was not measured. Her condition then remained static with occasional absence seizures. At age 22, she developed paroxysmal episodes of chorea in the neck, arms, and trunk associated with drowsiness, triggered by fever or hot weather (video 1). These occurred 4-5 times a year, lasting from 1 to 10 minutes. In all episodes, she remained responsive to verbal stimuli. Prolonged interictal video EEGs showed intermittent 4-6 Hz generalized epileptiform discharges, although no motor events were recorded.

Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

“…PxDs have been reported in a number of neurometabolic diseases, including Wilson, Lesch-Nyan and maple syrup urine disease (MSUD) and GABA transaminase deficiency [272][273][274][275].…”

Catching the Culprit: How Chorea May Signal an Inborn Error of Metabolism

“…The 76 studies included in this review [ 16 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 ] were published between 1964 [ 39 ] and 2022 [ 80 ] and were conducted in various countries (Table S2). Of these, 30 were case reports, and 46 were case series.…”

“…Tongue involvement was noted in some patients, including those with glutaric aciduria type 1, mucopolysaccharidosis type 2, metachromatic leukodystrophy and succinic semialdehyde dehydrogenase deficiency. Additionally, there were reports of paroxysmal episodes in GABA transaminase deficiency involving the neck, arms, and trunk, accompanied by drowsiness and triggered by fever or hot weather [ 69 ]. Chorea distribution information was unavailable for 129 (74.5%) individuals.…”

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

“…In a similar manner, dystonic head tremor observed in AFG3L2-spinocerebellar ataxia type 28 • OTC-Ornithine transcarbamylase deficiency (137,138) • ABAT-GABA transaminase deficiency (139) • ALDH5A1-Succinic Semialdehyde Dehydrogenase Deficiency (140) • PARK2-Parkin deficiency (141) protein-2 deficiency (74) gives an excellent clue for the diagnosis of the IEMs.…”