|Year : 2022 | Volume
| Issue : 3 | Page : 70-72
A case of giant axonal neuropathy
Jo Martin Kuncheria1, A Shanavas2
1 Department of Pediatrics, Government TD Medical College, Alappuzha, Kerala, India
2 Department of Pediatrics, Government Medical College, Kollam, Kerala, India
|Date of Submission||31-Mar-2023|
|Date of Decision||19-Apr-2023|
|Date of Acceptance||21-Apr-2023|
|Date of Web Publication||29-Aug-2023|
Dr. Jo Martin Kuncheria
Department of Pediatrics, Government TD Medical College, Alappuzha 688005, Kerala
Source of Support: None, Conflict of Interest: None
Giant axonal neuropathy is a rare autosomal recessive disorder that results in progressive mixed peripheral neuropathy and degeneration of central white matter. Child has short frizzy hair, distichiasis, pes planus, scoliosis, symptoms suggestive of cerebellar involvement, hypotonia, and hyporeflexia. Nerve conduction study showed features of axonal neuropathy. Magnetic resonance imaging brain showed hyperintensities in periventricular and bilateral deep cerebral white matter extending to involve the posterior limb of internal capsule, brain stem and cerebellar white matter. Clinical exome sequencing was positive for giant axonal neuropathy. Conservative management was done including physiotherapy under PMR guidance, family counseling, and follow-up care.
Keywords: Giant axon, gigaxonin, neuropathy
|How to cite this article:|
Kuncheria JM, Shanavas A. A case of giant axonal neuropathy. Pediatr Companion 2022;1:70-2
| Introduction|| |
Giant axonal neuropathy is a rare autosomal recessive disorder that results in progressive mixed peripheral neuropathy and degeneration of central white matter. Mutations in GAN gene located on Chr. 16q24 result in defective protein gigaxonin which is a part of ubiquitin proteasome system which helps in the breakdown of neurofilaments. Characteristic clinical features include Ataxia and Nystagmus with signs of peripheral neuropathy.
| Clinical presentation|| |
A 7-year-old male child born out of 3rd degree consanguineous marriage presented with progressively worsening unsteadiness of gait and frequent falls since 4 years of age. There was no history of seizures, abnormal sensorium or cranial nerve involvement. Developmental milestones were achieved normally. Child had wide based gait [Figure 1], short frizzy hair [Figure 2], distichiasis, pes planus [Figure 3], and scoliosis. At admission, the child was as alert and active. No pallor, icterus, cyanosis, clubbing, lymphadenopathy, or oedema were present. Vitals were found to be stable. Anthropometry showed normal growth parameters. Central nerve system examination showed normal higher mental functions. Cranial nerves were normal. No muscle wasting present and grade 4 power was present in all muscles. Generalized hypotonia and hyporeflexia were present with plantar mute. Cortical and peripheral sensations were well preserved. Cerebellar involvement includes wide based gait [Figure 1], intention tremor, past pointing, scanning speech, and macrographia. Cardiovascular, abdominal, and respiratory examinations were normal.
Investigations showed normal blood routine values, thyroid function test, gas chromatography mass spectrometry, and tandem mass spectrometry. Nerve conduction study showed sensory motor axonal polyneuropathy. Magnetic resonance imaging of brain [Figure 4] showed hyperintensities in Cerebellar & brain stem white matter, periventricular and B/L deep cerebral white matter. Clinical exome sequencing showed GAN-1 mutation.
|Figure 4: Magnetic resonance imaging brain, T2/FLAIR hyperintensities in cerebellar and brain stem white matter, periventricular and B/L deep cerebral white matter|
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| Discussion|| |
Giant axonal neuropathy is a chronic polyneuropathy of childhood with brain and peripheral nerve involvement. Possibilities of metachromatic leukodystrophy and giant axonal neuropathy (in view of kinky hair) were considered. Diagnosis was done by nerve conduction study which showed low amplitude and low velocity; brain magnetic resonance imaging showed hyperintensities in deep white matter, and clinical exome sequencing showed GAN-1 gene mutation. Nerve biopsy if done may show giant axon.,
Mutations in GAN gene located on Chr. 16q24 result in defective protein gigaxonin which is a part of ubiquitin proteasome system which helps in the breakdown of neurofilaments. This results in axonal loss and giant axonal swellings filled with neurofilaments. Also, there is general proliferation of intermediate filaments including glial filaments in brain, cytokeratin in hair and vimentin in schwann cells and fibroblasts.
Treatment is mainly supportive. Conservative management with a medical team including pediatric neurologist, physiotherapy done under PMR guidance, together with Speech and Occupational therapy should be considered. Family counseling and follow-up care should be done.
| Prognosis|| |
There will be gradual decline in mental function with loss of control of body movements, seizure, and the person may become wheelchair dependent in the second decade of life.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Kliegman RM, Joseph W Nelson Text Book of Pediatrics. Neuromuscular Disorders. 21st ed. Elsevier Inc; 2020. p. 3328.
Yuan Y, Bergmann M, Gerfelmeyer G, Kuchelmeister K Die Riesenaxonneuropathie. Eine Kasuistik. Giant axonal neuropathy. A case report 1996;17:213-8..
Nafe R, Trollmann R, Schlote W The giant axonal neuropathy—Clinical and hisotological aspects, differential diagnosis and a new case. Clin Neuropathol 2001;20:200-11.
Kamate M, Ramakrishna S, Kambali S, Mahadevan A Giant axonal neuropathy: A rare inherited neuropathy with simple clinical clues. BMJ Case Rep 2014;2014: bcr2014204481.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]