Phenotype Variability of Infantile-Onset Multisystem Neurologic, Endocrine, and Pancreatic Disease IMNEPD

Abstract

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.

Novel PTRH2 gene variant causing IMNEPD (infantile-onset multisystem neurologic, endocrine, and pancreatic disease) in 2 Saudi siblings

“…3) Another study reported development of antibody negative diabetes (HbA1c value 10.2%) with neuro cognitive impairment and deafness at the age of 13 year emphasized on regular monitoring of diabetes. 10) We herein recommend regular check of glycosylated hemoglobin after the 1st decade of life and encourage to do a neuroimaging at diagnosis and follow-up especially if the patient has neurological manifestation.…”

“…The youngest age when diabetes was discovered was 12 years of age [ 3 ]. Another study reported development of antibody negative diabetes (HbA1c value 10.2%) with neuro cognitive impairment and deafness at the age of 13 year emphasized on regular monitoring of diabetes [ 10 ].…”