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Woodhouse-Sakati Syndrome is a very rare autosomal recessive disorder caused by pathogenic variants in the DCAF17 gene, which encodes DDB1-and CUL4-associated factor 17. It is a multisystemic disorder characterized by hypogonadism, adolescent-to young adult-onset diabetes mellitus, hypothyroidism, and alopecia. Neurologic involvement includes childhood-onset moderate bilateral sensorineural hearing loss, mild intellectual disability adolescent-to young adult-onset of extrapyramidal findings, dysarthria, and dysphagia. Brain imaging typically reveals iron deposition in the globus pallidus and periventricular leukodystrophy. We report the case of a 31-year-old Portuguese female, the only child of a consanguineous couple. She presented with cognitive impairment, spastic paraparesis, lower limb dystonia, dysarthria, and dysphagia. She also had hypergonadotrophic hypogonadism associated with primary amenorrhea, insulin-dependent diabetes mellitus with retinopathy, primary hypothyroidism, moderate bilateral sensorineural hearing loss, and alopecia. Serial brain magnetic resonance imaging showed a progressive periventricular leukodystrophy with pontine involvement and significant bilateral iron deposition in the globus pallidus, substantia nigra, and red nucleus.

ObjectiveTo perform a systematic analysis and scoring of brain MRI white matter hyperintensities (WMH) in adult-onset Krabbe disease.MethodsWe retrospectively collected basic clinical data and the first available brain MRI from patients with confirmed Krabbe disease with first clinical manifestations beyond 10 years of age. Data were obtained from our reference center for lysosomal diseases (n = 6) and from contacted authors of published articles describing patients with adult-onset Krabbe disease (n = 15). T2-weighted fluid-attenuated inversion recovery images of each patient were analyzed and scored using a radiologic score of WMH in a single center.ResultsThe corticospinal tract was always affected by WMH (100% of patients), however, with some distinctions along the tract: the precentral gyrus (100%), corona radiata (95%), and posterior internal capsule (81%) were highly abnormal, whereas the mesencephalon (57%), pons (52%), and medulla oblongata (5%) were less affected. WMH were also frequently present in the posterior lateral periventricular white matter (95%), optic radiations (86%), postcentral gyrus (71%), medial lemniscus (62%), and corpus callosum, especially in the isthmus (71%), whereas the genu was always normal. A few patients did not have the classical MRI pattern but extensive hyperintensities (n = 3), or patchy distribution of hyperintensities mimicking an acquired etiology (n = 2), or very subtle hyperintensities of the corticospinal tract (n = 1).ConclusionsWe specified the main locations of WMH, which were observed in the earliest stages of the disease and were also present in patients with atypical MRI pattern, highlighting the importance of radiologic features to guide the diagnosis.