RESUMO
Sanfilippo Syndrome, or mucopolysaccharidosis type III (MPS III), is a group of autosomal-recessive lysosomal storage disorders leading to tissue accumulation of heparan sulfate. MPS III is caused by deficiency in one of 4 enzymes involved in lysosomal degradation of heparan sulfate. Based on the relevant enzyme deficiency, 4 types have been recognized. MPS III constitutes a progressive neurodegenerative and systemic disorder. Parents of children diagnosed with MPS III were interviewed using a retrospective questionnaire based on the known clinical manifestations of MPS III. Eight patients from 4 unrelated families of varied ethnic origin were included. All children were diagnosed with MPS type III-A. Average age at diagnosis was 6.1 years. The most common early clinical manifestations leading to parental suspicion of illness were speech delay and coarse facial features. All children were reported to have global developmental delay, sleep disorders, recurrent infections, hyperactivity, and decreased hearing. The time from first medical inquiry until diagnosis was over 2 years on average, consistent with the delay in diagnosis described in the literature. MPS III children frequently undergo early and repeated ear, nose and throat surgeries, thus we suggest that a high index of suspicion is warranted in relevant clinical circumstances.
RESUMO
BACKGROUND: Mucolipidosis type IV (ML-IV) is a rare autosomal-recessive lysosomal storage disease, caused by mutations in MCOLN1. ML-IV manifests with developmental delay, esotropia and corneal clouding. While the clinical phenotype is well-described, the diagnosis of ML-IV is often challenging and elusive. OBJECTIVE: Our experience with ML-IV patients brought to the clinical observation that they share common and identifiable facial features, not yet described in the literature to date. Here, we utilized a computerized facial analysis tool to establish this association. METHODS: Using the DeepGestalt algorithm, 50 two-dimensional facial images of ten ML-IV patients were analyzed, and compared to unaffected controls (n = 98) and to individuals affected with other genetic disorders (n = 99). Results were expressed in terms of the area-under-the-curve (AUC) of the receiver-operating-characteristic curve (ROC). RESULTS: When compared to unaffected cases and to cases diagnosed with syndromes other than ML-IV, the ML-IV cohort showed an AUC of 0.822 (p value < 0.01) and an AUC of 0.885 (p value < 0.001), respectively. CONCLUSIONS: We describe recognizable facial features typical in patients with ML-IV. Reaffirmed by the DeepGestalt technology, the described common facial phenotype adds to the tools currently available for clinicians and may thus assist in reaching an earlier diagnosis of this rare and underdiagnosed disorder.
