Introduction:
Ataxia in children is a common clinical sign of various disorders
consisting of discoordination of movement with an absence of muscle
control during voluntary activity. Ataxia is generally caused by
disorder in function of the complex circuitry connecting the basal
ganglia, cerebellum, and cerebral cortex, and this is known as
“cerebellar ataxia.” A wide variety of disorders can lead to acquired
and inherited ataxia. Prompt identification of etiologies in progressive
ataxic disorders is important, because corrective treatments may halt
the degenerative process and preserve cerebellar functioning. (1) Some
causes of ataxia in children and adolescents which are treatable include
coenzyme Q10 (CoQ10) deficiency, ataxia with vitamin E deficiency
(AVED), Niemann-Pick Type C (NPC) disease, Friedrich’s ataxia, and
Cerebrotendinous xanthomatosis (CTX). (2)
Primary coenzyme Q10 (CoQ10) deficiency is a group of cerebellar ataxias
with mitochondrial respiration disorders caused by autosomal recessive
multi genetic mutations. The features of primary CoQ10 deficiency
include early-onset exercise intolerance, progressive cerebellar ataxia,
intellectual disability, seizure, stroke-like episodes, mitochondrial
myopathy, hypogonadism, and steroid-resistant nephrotic syndrome, with
the age at onset ranging from infancy to late adulthood. (3) CoQ10
measurement in skeletal muscle and replacement with CoQ10 30 mg /kg/day
orally can be helpful. (2)
Ataxia with vitamin E deficiency (AVED) is a rare, autosomal recessive
neurodegenerative disorder, with mutations in the gene encoding the
a-tocopherol transfer protein (TTPA/aTTP) result in defective
transportation out of the liver and systemic vitamin E deficiency. (4)
Diagnostic test includes vitamin E levels and treatment is by vitamin E
(800 mg/d) in divided doses. (2)
Niemann-Pick Type C (NPC) disease is a rare genetic neurodegenerative
disease with clinical spectrum ranges from a prenatal disorder to an
adult-onset. The scarcity of the disease and the lack of expertise may
result in misdiagnosis, delayed diagnosis, and inadequate care. This
causes more physical, psychological, and intellectual deficits,
inappropriate treatment, and patient disempowerment. The diagnosis of
NPC is accompanied by improved quality of life if a diagnosis is made
promptly and appropriate comprehensive management is instituted. (5)
Serum oxysterol and NPC gene testing are considered as diagnostic tests
and treatment by Miglustat 600mg/day may be useful. (2)
Friedrich’s ataxia is characterized typically by progressive gait and
limb ataxia, loss of deep tendon reflexes, and dysarthria, hypertrophic
cardiomyopathy, diabetes, scoliosis, distal wasting, optic atrophy, and
sensorineural deafness. (6)
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively
inherited lipid storage disorder due to mutations of the CYP27A1 gene
result in defective enzyme activity of sterol 27-hydroxylase which
catalyzes the first step in the process of cholesterol side-chain
oxidation. It causes impaired primary bile acid synthesis, increased
concentration of bile alcohols, and increased formation of plasma and
tissue cholestanol. The symptoms of CTX are produced in part by the
accumulation of cholestanol and cholesterol in almost every tissue of
the body, particularly in the nervous system, atherosclerotic plaques,
and tendon xanthomata. Characteristic features of CTX include
intellectual disability, dementia, pyramidal and/or cerebellar signs,
peripheral neuropathy, and psychiatric disturbances. Xanthomas often
appear in the second or third decade. As the progressive neurological
findings present in early adulthood, initial symptoms consist of
prolonged neonatal jaundice, chronic infantile diarrhea, and juvenile
cataract. Brain imaging of patients reveals both supra and
infratentorial atrophy and parenchymal lesions in periventricular white
matter, globus pallidus and internal capsule, dentate nuclei, and
cerebellar white matter. (7)
Here, we provide the clinical presentation, genetic findings, treatment,
and outcome of 25 patients with treatable ataxia during the last 4
years.