ITPA Encephalopathy: A Unique Neuroradiology Pattern as a Hallmark of the Disease

Introduction: ITPA encephalopathy, described recently by Kevelam et al, is characterized by early onset encephalopathy, progressive microcephaly, seizures, variable cardiac defects, and early death. It is related to recessive pathogenic variants in ITPA gene which encodes an ITPase involved in purine metabolism. We present a case of ITPAencephalopathy and highlight the importance of the magnetic resonance imaging (MRI) pattern recognition.

Case Presentation: A 3 months old male presented, immediately after birth, with jitteriness and irritability, third son of healthy and nonconsanguineous parents. Pregnancy and delivery were uneventful. Metabolic and infectious screening was normal except for hyperproteinorrachia. At 3 months old, severe axial hypotonia, progressive microcephaly, and lack of visual contact were evidenced. Seizures onset was at 6 months, being refractory to antiepileptic drugs. Brain MRI showed a distinct pattern characterized by bilateral and symmetric high T2 signal and decreased diffusion in diffusion-weighted image in the posterior limb of the internal capsule, cerebellar superior peduncles, and cerebral peduncles. The neuroimaging pattern lead us to suspect ITPA encephalopathy and two pathogenic variants in ITPA were found as well as severely decreased enzyme activity in fibroblasts. Parents were carriers of one of the mutations. The patient died at 10 months because of an epileptic decompensation in the context of a respiratory infection.

Conclusion: ITPA encephalopathy is a devastating disorder of purine metabolism without a specific metabolic biomarker. The brain MRI pattern is the hallmark of the disease. Despite not having treatment available, genetic confirmation is useful to avoid unnecessary tests, genetic counseling, and advice about patient clinical outcome.