A "Hot Cross Bun" sign on T2-weighted MRI was described as a result of selective loss of myelinated transverse pontocerebellar fibers and neurons in the pontine raphe with preservation of the pontine tegmentum and corticospinal tracts (CST). However, neuropathologic studies showed contradicting results with no sparing of the CST. This is a pictorial and quantitative demonstration of the sign on diffusion tensor imaging and tractography, which provides the imaging evidence that is consistent with neuropathologic findings.
Inborn errors of metabolism can cause epileptic encephalopathies. Biallelic loss-of-function variants in the ITPA gene, encoding inosine triphosphate pyrophosphatase (ITPase), have been reported in epileptic encephalopathies with lack of myelination of the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices (MIM:616647). ITPase plays an important role in purine metabolism. In this study, we identified two novel homozygous ITPA variants, c.264-1 G > A and c.489-1 G > A, in two unrelated consanguineous families. The probands had epilepsy, microcephaly with characteristic magnetic resonance imaging findings (T2 hyperintensity signals in the pyramidal tracts of the internal capsule, delayed myelination, and thin corpus callosum), hypotonia, and developmental delay; both died in early infancy. Our report expands the knowledge of clinical consequences of biallelic ITPA variants.