Psychiatric symptoms and CK-Elevation as initial manifestations of late-onset Tay-Sachs disease

Medical History: In a 15 year old boy who was treated in the Department of Child Psychiatry due to a bipolar disorder a routine blood check revealed a CK-Elevation of 1100U/l. The medical treatment of the psychiatric disease was difficult. The patient reported muscular cramps that appear especially while distension and sometimes while physical training and some difficulties in climbing steps. Clinical examination showed muscle contractions after percussion, but no other signs of myotonia. There was mild proximal weakness with a postive Gowers sign.

Diagnostic Investigation: Initial MRI of the brain (1.5 years before first seen in the Neuropediatric Department) and EEG were normal. Muscle biopsy revealed grouped fibre atrophy with small groups of angulated fibers and target fibers, suggestive of a motor neuron disease. Cerebrospinal fluid was normal, especially no dysfunction of the blood-brain barrier. Neurophysiological examination revealed normal peripheral nerve conduction, but signs of denervation. Follow-up MRI showed widened supra- and infratentorial subarachnoid spaces and no abnormalities of the spinal cord. Due to the combination of a psychiatric disease with a motor neuron disorder lysosomal enzymes were analyzed. This showed a strongly reduced activity of the Hexosaminidase A. Sequencing of the HEXA-Gen showed heterocygote mutations (Exon 3 c.409C>T, Exon 7 c.805G>A), which were present in one parent each, confirming the diagnosis of a late-onset Tay-Sachs disease.

Conclusion: Late-onset Tay-Sachs disease is a rare, progressive neurologic disease. Early in the course not only neurological problems such as motor neuron disease, ataxia, difficulties in swollowing and dysarthria, but also psychiatric symptoms can appear. This case illustrates a psychiatric problem can be the leading symptom in late-onset Tay-Sachs disease.