Abstract
OBJECTIVES: The objective of this study was to expand the phenotypic spectrum of infantile-onset multisystem neurologic, endocrine, and pancreatic disease type 1 (IMNEPD1) and highlight the importance of analyzing the PTRH2 gene in patients with neuropathy presenting with pancreatic lipomatosis. METHODS: Two sisters, aged 73 and 71 years, respectively, presented a severe, length-dependent sensorimotor axonal neuropathy, associated with deafness and intellectual deficiency. RESULTS: They both needed a wheelchair from the fourth decade. They developed a severe respiratory dysfunction, requiring nocturnal noninvasive ventilation from around 50 years of age. The younger sister developed severe dysphagia complicated by aspiration pneumonia. A muscle biopsy of the younger sister was suggestive of mitochondrial myopathy. The youngest presented a complete pancreatic lipomatosis. A biallelic novel likely pathogenic variant within PTRH2, c.254A>G (p.Gln85Arg), was evidenced in both patients. DISCUSSION: IMNEPD1 is a rare autosomal recessive disorder caused by sequence variant in the PTRH2 gene and characterized by a peripheral neuropathy, cerebellar atrophy, intellectual disability, hearing loss, pancreatic insufficiency, hypothyroidism, and dysmorphic features. In addition to these classic manifestations of the disorder, severe dysphagia and respiratory insufficiency may develop over the course of the disease and should be systematically screened. PTRH2 gene should be considered in patients with pancreatic lipomatosis and neuropathy.