Spinocerebellar Ataxia Type 34: ELOVL4 Recurrent Mutation in a Different Family

Dear Editor,

Spinocerebellar ataxias (SCA) are a group of autosomal dominant neurodegenerative conditions resulting in cerebellar manifestations mainly ataxia and eye movement abnormalities.¹ Variable phenotypes exist, including ataxia, peripheral neuropathy, parkinsonism, cognitive decline, retinopathy, seizures, and skin manifestations.² There are currently about 50 different SCA subtypes classified based on genetic mutations, last being SCA51 described recently.³ Very-long-chain fatty acid elongase (ELOVL) enzymes are implicated in the elongation of very-long-chain fatty acids (VLCFA). Mutations of their enzymes cause SCA34 and 38.⁴ SCA34 represents a clinical entity manifesting with a hallmark of ataxia and skin lesions resolving in adulthood, in particular erythrokertodermia variabilis, an entity of migratory patches and hyperkeratotic plaques. Other reported clinical manifestations included gaze, nystagmus, hyperreflexia, and peripheral neuropathy.⁵,⁶ We present the second case in literature of SCA34 with newly discovered mutation c.512T>C (p.I171T) in a Vietnamese patient.

A 49-year-old woman presented to our clinic with progressively worsening gait and recurrent falls since age 32. She reported having hand tremors and problems with manual dexterity, affecting tasks such as dressing. She experienced vertigo episodes and reported intermittent urinary incontinence. Despite her symptoms, she maintained a rigorous daily exercise regimen and required no assistive devices. Prior to presenting to our clinic, she was prescribed clonazepam 0.5 mg nightly, which provided some relief from her tremors. The patient is Vietnamese and has an affected mother who is currently 76 years old. Her mother developed gait instability around age 60 with tremors in both arms and now relies on a walker to ambulate. The patient's four siblings reportedly have gait impairment as well, and her three children are currently asymptomatic.

On clinical examination (Supplementary Video 1 in the online-only Data Supplement), the patient exhibited scanning dysarthria, positive square wave jerks, and horizontal greater than vertical hypometric saccades. There was coarse vertical nystagmus on upgaze. She displayed impaired performance in finger-nose-finger testing—overshooting intended targets. Subtle outflow tremor was also evident. Rapid sequential movements exhibited mild slowing in the distal extremities. Heel-to-shin coordination was ataxic. Patient had a wide-based gait and was unable to tandem. Hyperreflexia was evident, marked by a positive bilateral Hoffman's sign. Vibratory sensation in the lower extremities was reduced. There was absence of dermatological lesions or retinal findings as per a retina examination performed by an ophthalmologist.

Assessments of ceruloplasmin, vitamin B12, folate, thyroid-stimulating hormone, alpha-fetoprotein, gliadin deamidated antibody, vitamin E, and vitamin B1 were negative. Brain MRI revealed cerebellar atrophy while MRI of the cervical spine showed evidence of mild stenosis without cord signal. Genetic testing was obtained and yielded a positive mutation c.512T>C (p.I171T) in ELOVL4 gene encoding SCA34.

She was initiated on carbidopa/levodopa (300 mg daily), which provided mild improvement in ambulation when combined with physical therapy.

The typical clinical presentation of SCA34 encompasses slowly progressive adult-onset ataxia, often accompanied by constellation of neurological symptoms. Recently, mutations in ELOVL4 and ELOVL5 have been described to result in SCA wherein ELOVL4 was associated with SCA34⁷ and ELOVL5 was linked to SCA38.⁸ The location of ELOVL enzymes within specific tissues may contribute to the unique clinical profiles observed in these cases. Phenotypic variability could be related to the type of the VLCFA involved in the metabolism by the mutated elongase. Certain mutations of ELOVL4 might affect saturated VLCFA metabolism while polyunsaturated VLCFA remain unaffected.⁹ This differential synthesis might produce a variable clinical picture. In the case of our patient, a manifested syndrome of ataxia, nystagmus, hyperreflexia and early peripheral neuropathy was produced, without skin changes or retinal degeneration.

Several mutations have been reported to affect ELOVL4 gene resulting in SCA34 phenotype. In a recent publication, the genetic mutation present in our patient (c.512T>C (p.I171T)) was documented within a family of American heritage.⁵ In this family, there were no skin findings, and only half the members manifested retinitis pigmentosa. Notably, our case represents only the second instance where this specific mutation has been identified. While our patient did not have clinical signs of parkinsonism, L-dopa was tried with ultimate efficacy based on benefits reported with SCA2 and 3.¹⁰ It is worth highlighting that our patient is originally Vietnamese which distinguishes this case from previously reported American family. The sporadic nature of this genetic mutation occurrence raises the possibility that it may manifest independently, irrespective of ethnic background.

Supplementary Material

The online-only Data Supplement is available with this article at https://doi.org/10.3988/jcn.2025.0023.

Video 1

Clinical examination of the patient revealing appendicular and axial ataxia with wide based gait.

Availability of Data and Material

All data generated or analyzed during the study are included in this pub lished article (and its supplementary information files).