Slowly progressive cerebellar ataxia in a 12-year-old Indian boy with early onset anterior horn cell spinal muscular atrophy is reported from the Department of Pediatric Neurology, Government Medical College, Kerala, India. Born of nonconsanguineous parents, he was hypotonic at birth, milestones were delayed, and he had frequent respiratory infections and fluid aspirations. At 12 years, he walked with a wide based ataxic gait, his muscles were wasted and hypotonic, and reflexes were absent. Bilateral gaze nystagmus, past pointing, and dysdiadochokinesia were noted. EMG showed fibrillations, fasciculations, and polyphasic potentials, and muscle biopsy showed evidence of denervation, with variation in fiber size and group atrophy compatible with spinal muscular atrophy type 3. MRI showed marked atrophy of the cerebellar vermis and hemispheres, and prominent cisterna magna and prepontine cisterns. Molecular genetic testing for SMN1 on chromosome 5q showed no deletions at exon 7 and 8. Mitochondrial disease was excluded. Serum transferrin test for carbohydrate-deficient glycoprotein syndrome was not available. This case represents a mild variant of pontocerebellar hypoplasia type 1. [1]

COMMENT. In the diagnostic work-up of a child with slowly progressive cerebellar ataxia, a large spectrum of neurodegenerative and metabolic disorders needs to be considered. Hereditary and sporadic ataxias are the two major categories. Hereditary cases are autosomal dominant, autosomal recessive, X-linked, or mitochondrial. Sporadic cases are symptomatic (structural lesions, developmental, neoplastic, toxic, drug-induced, endocrine [hypothyroidism], malabsorption [celiac disease], paraneoplastic, demyelinating, and inflammatory), and idiopathic. Classifications of the ataxias have evolved over time. Originally based on neuropathologic criteria, more recently, a clinical classification was introduced [2]. The latest classification is genotype-based and presents a challenge in distinguishing the various clinical and hereditary characteristics of multiple subtypes and choice of genetic test. With rare ataxia variants, a complete ataxia battery at a cost of -$8000 sometimes seems more appropriate than the selection of one test at $600 or a smaller battery, among a total of 17 tests offered, with selection based on the clinical syndrome. Having ruled out symptomatic causes that may be treatable, the diagnosis of hereditary ataxia is important for prognosis, genetic counseling, and possible therapeutic interventions. A diagnostic algorithm presented for adult onset cerebellar ataxias [3] may overlap with childhood ataxias, but during childhood, congenital and metabolic disorders are more frequent. In some cases, the progression of clinical ataxia and MRI evidence of cerebellar atrophy may be very slow and imperceptible. The sudden onset of strabismus or other oculomotor sign is a more definite marker of progression, requiring immediate specific genetic and prognostic classification preliminary to corrective surgery.

In the above case of pontocerebellar hypoplasia with spinal muscular atrophy the slow progression of ataxia is unusual, since most reports indicate a rapid progression with death in infancy [4]. A Pubmed search of the literature uncovered several cases of olivopontocerebellar atrophy associated with carbohydrate-deficient glycoprotein (CDG) syndrome type 1 that was recognized at a later age [5]. The serum transferrin test for CDG syndrome would be of interest in the above case. [6]