Mitochondrial cytopathies are a genetically and phenotypically heterogeneous group of disorders that range from systemic, lethal pediatric disease to late-onset, tissue-specific neurodegenerative disorders.1 Neurological complications such as mitochondrial encephalomyopathy with lactic acidosis and stroke (MELAS) have been described.2 Psychiatric symptoms reported to be occasionally associated with mitochondrial myopathies include dementia, atypical psychosis, depression and schizophrenia-like psychosis.3,4 We report a case of mitochondrial disease that presented with manic, catatonic and neurological symptoms.
A 16-year-old adolescent boy presented with an illness of 8 months duration that started acutely with symptoms of cheerfulness, overtalkativeness, overfamiliarity, grandiosity, imcreased self-care, echopraxia, decreased need for sleep and increased appetite for initial 4 weeks followed by refusal to eat, decreased speech output, decreased sleep, generalized rigidity of all four limbs, left-sided limb weakness, flexion and internal rotation at elbow and hemiplegic gait for the next 7 months. The patient’s paternal uncle had symptoms suggestive of a psychotic illness. The patient was started on multiple anticonvulsants, antipsychotics and antidepressants by a general physician, who discontinued these medications after 3 days because the patient developed drooling of saliva, painful hyperextension of neck and back, worsening of rigidity, staring, posturing, stereotypic movements of hand, negativism, mutism and impairment in activities of daily living, for which he underwent five sessions of electroconvulsive therapy. At presentation to Postgraduate Institute of Medical Education and Research, Chandigarh, India, the patient was also noted to have gegenhalten, extensor posturing, episodes of opisthotonous (up to 40 episodes of approx. 10–75 min per day) and dynamic contractures at the knee, ankle and wrist joints. Routine investigations did not reveal any abnormality. Serum lactate was elevated (approx. twice the upper limit of normal range). Magnetic resonance imaging (MRI) of the brain showed hyperintensities in bilateral basal ganglia in both T1 and T2 images and single-photon emission computed tomography (SPECT) revealed grossly impaired perfusion in right-sided thalamus. Electron microscopic examination of muscle tissue obtained on biopsy showed sub-sarcolemmal and inter-myofibrillar accumulations of abnormal-looking mitochondria, consistent with the diagnosis of mitochondrial myopathy. Patient had negative KF ring, and serum ceruloplasmin, serum copper, urinary copper and liver ultrasound were normal. Cerebrospinal fluid cytology, biochemistry, adenosine deaminase, and polymerase chain reaction for tuberculosis were negative. He was treated with diazepam 40 mg/day and quitiapine 175 mg/day, on which his rigidity, episodes of opisthotonous, gegenhalten, posturing and motor stereotypy improved. Improvement was maintained even after decreasing diazepam to 5 mg and quetiapine to 100 mg. Physiotherapy for knee and ankle contractures was initiated and partial improvement in activities of daily living was noted.
The classical form of MELAS is characterized by early onset stroke-like episodes (before age 40), encephalopathy (seizures, dementia), lactic acidosis, and ragged red fibers on muscle biopsy.5 The index patient had most features of MELAS but was atypical in that he initially had manic and then catatonic symptoms and it was difficult to comment on his cognitive functions (owing to catatonic symptoms like muteness). Absence of family history of mitochondrial myopathy in the index case should not be considered an atypicality.2 Hyperintensities in bilateral basal ganglia (MRI) may explain the presence of prominent extrapyramidal symptoms, and gross impairment of perfusion of right-sided thalamus (SPECT) may explain the manic symptoms. The present report highlights the fact that in patients presenting with psychiatric and neurological symptoms, the possibility of mitochondrial encephalomyopathy should be considered.