Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder caused by mutations in EIF2AK3 and is the commonest cause of permanent neonatal diabetes mellitus in highly consanguineous populations.
This protocol addresses permanent neonatal diabetes arising from an EIF2AK3 mutation in the presence of coexisting spondyloepiphyseal dysplasia and episodes of recurrent hepatic and/or renal dysfunction — the defining multisystem triad of Wolcott-Rallison syndrome.
Management centres on insulin therapy for the diabetes component; the full protocol additionally specifies how to approach severe hepatic complications when they arise.
This rare autosomal recessive syndrome is the commonest cause of PNDM in highly inbred populations and characterized by early-onset diabetes mellitus, spondyloepiphyseal dysplasia, and recurrent hepatic and/or renal dysfunction.
Apart from KATP-NDM and some persons with SLC19A2 mutations causing thiamine-responsive megaloblastic anemia (TRMA) syndrome, all other causes need to be treated with subcutaneous insulin.
Fulminant hepatic failure is the main cause of death in persons with WRS and currently there is no agent to reverse this abnormality; however, recent reports indicate that liver (with or without pancreas) transplantation can be life saving and improve the outcomes of individuals with this syndrome.
DOI: 10.1111/pedi.13426
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