Medical Case: A toddler with progressive ataxia

Correct answer: B. Serum coeliac disease screening (IgA anti-tissue transglutaminase antibodies)

In a child with progressive ataxia and an unrevealing neurological work-up, it is appropriate to broaden the differential diagnosis beyond primary neurological disorders. Coeliac disease should be considered in patients with otherwise unexplained ataxia, and serological testing represents a reasonable next diagnostic step.

Repeating brain MRI would be unlikely to provide additional diagnostic value after a normal study unless new neurological red flags emerged.

Genetic testing for hereditary ataxias may be considered in the evaluation of progressive cerebellar syndromes. However, these conditions are rare in very young children and are generally investigated after more common acquired or systemic causes have been considered.

Autoimmune cerebellar syndromes associated with antibodies such as anti-GAD are also part of the differential diagnosis of ataxia. In this case, however, the clinical picture lacks additional features that would typically prompt targeted autoimmune testing, such as other autoimmune manifestations or evidence of central nervous system inflammation. In contrast, coeliac serology represents a pragmatic screening test that should be considered in otherwise unexplained ataxia.

Screening for coeliac disease with IgA anti-tissue transglutaminase antibodies (tTG-IgA) therefore represents the most appropriate next investigation.

Diagnosis and clinical course

Serological testing for coeliac disease was performed and revealed markedly elevated tTG-IgA levels (>10× the upper limit of normal). Endomysial antibodies (EMA) were also positive.

In the presence of strongly positive serology, current paediatric diagnostic algorithms allow the diagnosis of coeliac disease without intestinal biopsy in selected cases, particularly when tTG titres exceed ten times the upper limit of normal and EMA are positive.

Emma was therefore diagnosed with coeliac disease presenting with neurological manifestations.

A strict gluten-free diet was initiated. Over the following weeks, her parents noticed progressive improvement in balance and gait stability. At follow-up approximately one month after starting the diet, Emma’s neurological symptoms had completely resolved, and she had returned to her baseline level of activity.

Discussion

Coeliac disease is an immune-mediated disorder triggered by gluten ingestion in genetically susceptible individuals. Although the condition is classically associated with gastrointestinal symptoms and intestinal inflammation, extraintestinal manifestations are increasingly recognised, including neurological complications.

Among these neurological presentations, ataxia is one of the best described manifestations associated with gluten-related disorders, particularly in adults. Reports in paediatric populations are less common, and the clinical spectrum remains incompletely defined.

From a clinical perspective, this has important diagnostic implications. A recent review addressing the question of who should be tested for coeliac disease emphasises that coeliac disease should be considered in patients with otherwise unexplained ataxia, highlighting the importance of including the condition in the differential diagnosis when routine neurological investigations fail to identify a cause.

The mechanisms underlying gluten-related neurological manifestations are not fully understood. Immune-mediated processes have been proposed, and antibodies targeting different transglutaminase isoforms, including those expressed in neural tissues, have been investigated in patients with gluten-related neurological disorders. However, these biomarkers remain an area of ongoing research and their role in routine clinical practice is still evolving.

Neurological involvement in coeliac disease is not limited to ataxia. Other movement disorders have also been reported in association with gluten enteropathy. For example, a recent case report described a child presenting with chorea who was ultimately diagnosed with coeliac disease after an extensive neurological evaluation.

Taken together, these observations suggest that coeliac disease may occasionally present with neurological symptoms and that screening should be considered in children with otherwise unexplained movement disorders or progressive ataxia.

Take-home messages

1. Progressive ataxia in childhood has a broad differential diagnosis and may require evaluation beyond primary neurological disorders.
2. Coeliac disease should be considered in patients with otherwise unexplained ataxia.
   
3. Neurological manifestations may occur even in the absence of prominent gastrointestinal symptoms
4. Early recognition is important, as initiation of a gluten-free diet may lead to significant or complete neurological recovery.