Wolcott-Rallison syndrome

A rare hereditary autosomal recessive disorder characterized by permanent neonatal or early infancy type 1 diabetes mellitus. Epiphyseal dysplasia, OSTEOPOROSIS, and growth retardation develop at a later age. Affected individuals may also present with LIVER DISEASE; KIDNEY DISEASE; INTELLECTUAL DISABILITY, and CARDIOVASCULAR ABNORMALITIES. Mutations in the EIF2AK3 gene have been identified. OMIM: 226980

Also Known As:

Networked: 37 relevant articles (1 outcomes, 0 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hypothyroidism
2.	Permanent Neonatal Diabetes Mellitus
3.	Osteochondrodysplasias (Spondyloepiphyseal Dysplasia)
4.	Type 1 Diabetes Mellitus (Autoimmune Diabetes)
5.	Renal Insufficiency (Renal Failure)

Experts

1.	Nicolino, Marc: 5 articles (11/2015 - 07/2004)
2.	Cavener, Douglas R: 3 articles (11/2021 - 08/2003)
3.	Julier, Cécile: 3 articles (11/2015 - 07/2004)
4.	Senée, Valérie: 3 articles (11/2015 - 07/2004)
5.	McGrath, Barbara C: 2 articles (11/2021 - 08/2003)
6.	Harding, Heather P: 2 articles (11/2015 - 12/2002)
7.	Ron, David: 2 articles (11/2015 - 12/2002)
8.	Vasiljevic, Alexandre: 2 articles (11/2015 - 08/2015)
9.	Delépine, M: 2 articles (11/2006 - 08/2000)
10.	Julier, C: 2 articles (11/2006 - 08/2000)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Wolcott-Rallison syndrome:

1.	Thyroid HormonesIBA 12/01/2014 - "We report on primary hypothyroidism, which has not been previously described, of a patient with Wolcott-Rallison syndrome due to novel mutation (W521X), who showed improved growth after thyroid hormone treatment. "
2.	Phosphotransferases (Kinase)IBA 11/15/2018 - "PERK variants had previously been identified in Wolcott-Rallison Syndrome, a rare autosomal recessive metabolic disorder, and these variants completely abrogated the function of PERK's kinase domain or prevented PERK expression. " 08/01/2003 - "Humans afflicted with the Wolcott-Rallison syndrome and mice deficient for PERK (pancreatic endoplasmic reticulum eIF2alpha kinase) show severe postnatal growth retardation. " 02/01/2003 - "Mutation of a kinase that regulates translation initiation has been implicated in the etiology of a monogenic form of diabetes known as Wolcott-Rallison syndrome. " 07/01/2002 - "Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene." 12/15/2015 - "The great preclinical promise of the pancreatic endoplasmic reticulum kinase (PERK) inhibitors in neurodegenerative disorders and cancers is marred by pancreatic injury and diabetic syndrome observed in PERK knockout mice and humans lacking PERK function and suffering from Wolcott-Rallison syndrome. "
3.	Insulin (Novolin)FDA Link 03/01/2015 - "Wolcott-Rallison syndrome (WRS) is an autosomal recessive disease, characterized by neonatal or early-onset non-autoimmune insulin-dependent diabetes. " 11/04/2010 - "Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disease, characterized by neonatal/early-onset non-autoimmune insulin-requiring diabetes associated with skeletal dysplasia and growth retardation. " 07/01/2006 - "Mutations in the EIF2AK3 gene have been identified in patients with Wolcott-Rallison syndrome - a rare autosomal recessive disorder associated with permanent neonatal insulin-dependent diabetes. " 12/01/2004 - "Mutations in the EIF2AK3 gene underlie susceptibility to the Wolcott-Rallison syndrome, which is a monogenic disease associated with insulin-deficient neonatal diabetes. " 08/01/2000 - "Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. "
4.	Peptide Initiation Factors (Initiation Factor)IBA 08/01/2008 - "Molecular analysis of the eukaryotic translation initiation factor 2alpha kinase gene (EIF2AK3) demonstrated a homozygous mutation, compatible with a diagnosis of Wolcott-Rallison syndrome (WRS). " 08/01/2000 - "EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome." 01/01/2019 - "Wolcott-Rallison syndrome (WRS) is caused by a biallelic mutation in the gene encoding eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) on chromosome 2p11.2. This condition is characterized by permanent early-onset diabetes mellitus, epiphyseal dysplasia, and hepatic dysfunction. " 11/01/2006 - "The first patient was diagnosed postmortally with Wolcott-Rallison syndrome, after her younger brother developed IDDM, and a homozygous mutation in the eukaryotic translation initiation factor 2-alpha kinase 3 was found. "
5.	Prokaryotic Initiation Factor-2IBA 01/01/2021 - "Objective: Wolcott-Rallison syndrome is a rare autosomal recessive inheritance disorder caused by the defectiveness of eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3), which encodes the PKR-like endoplasmic reticulum kinase (PERK). " 10/16/2023 - "Wolcott-Rallison syndrome is a rare cause of permanent neonatal diabetes mellitus caused by mutations in the eukaryotic translation initiation factor 2 alpha kinase 3 gene (EIF2AK3). "
6.	Eukaryotic Initiation Factor-2 (EIF 2)IBA 12/01/2002 - "PERK mutations are associated with the Wolcott-Rallison syndrome of infantile diabetes and mutations that prevent the alpha-subunit of eIF2 from being phosphorylated by PERK, block beta-cell development, and impair gluconeogenesis. " 09/01/2014 - "Wolcott-Rallison syndrome (WRS) is a very rare genetic disorder, which is transmitted by autosomal recessive inheritance and results from mutations in the gene encoding the eukaryotic initiation factor 2-α kinase-3 (EIF2AK3). "
7.	Proteins (Proteins, Gene)FDA Link 04/01/2011 - "In this research, two novel mutations identified in the Chinese boy locate in the catalytic domain of the EIF2AK3 gene, disrupting the ability of autophosphorylation, leading to the truncated proteins that are unable to phosphorylate the natural substrate, which are responsible for the phenotype of Wolcott-Rallison syndrome." 01/01/2020 - "Abbreviations: BiP, Binding immunoglobulin Protein ER; endoplasmic reticulum; ERAD, ER-associated protein degradation; IFN, interferon; IL, interleukin; JNK, c-Jun N-terminal kinase; KHE, proton-K+ exchanger; MODY, maturity-onset diabetes of young; PERK, PRKR-like ER kinase; SERCA, Sarco/Endoplasmic Reticulum Ca2+-ATPases; T1D, type 1 diabetes; T2D, type 2 diabetes; TNF, tumor necrosis factor; UPR, unfolded protein response; WRS, Wolcott-Rallison syndrome."
8.	JNK Mitogen-Activated Protein KinasesIBA 01/01/2020 - "Abbreviations: BiP, Binding immunoglobulin Protein ER; endoplasmic reticulum; ERAD, ER-associated protein degradation; IFN, interferon; IL, interleukin; JNK, c-Jun N-terminal kinase; KHE, proton-K+ exchanger; MODY, maturity-onset diabetes of young; PERK, PRKR-like ER kinase; SERCA, Sarco/Endoplasmic Reticulum Ca2+-ATPases; T1D, type 1 diabetes; T2D, type 2 diabetes; TNF, tumor necrosis factor; UPR, unfolded protein response; WRS, Wolcott-Rallison syndrome."
9.	Nonsense Codon (Nonsense Mutation)IBA 11/03/2021 - "We validated the CRBR strategy for human gene therapy by rescuing a mouse model of Wolcott-Rallison syndrome (WRS) with permanent neonatal diabetes caused by either a large deletion or a nonsense mutation in the PERK (EIF2AK3) gene. "
10.	NF-kappa B (NF-kB)IBA 08/01/2003 - "The absence of NF-kappaB-mediated transcription and its antiapoptotic function provides an explanation for why eIF2alpha kinase deficiency in diseases such as Wolcott-Rallison syndrome leads to cellular apoptosis and disease."

Therapies and Procedures

1.	Therapeutics 10/16/2023 - "The follow-up for 18 months after diagnosis is detailed, illustrating both the therapeutic success of subcutaneous insulin therapy and the ongoing complications that patients with Wolcott-Rallison syndrome are subject to." 06/27/2017 - "CONCLUSIONS Regardless of whether permanent neonatal diabetes mellitus is associated with Wolcott-Rallison syndrome or other genetic mutations, it is important to initially stabilize the infant and later do a genetic testing to see whether the infant can be given oral sulfonylureas or has to be given insulin therapy."
2.	Organ Transplantation 01/01/2020 - "The concept of organ transplantation as treatment for complex genetic conditions, including Wolcott-Rallison syndrome (WRS), continues to show promise. "
3.	Pancreas Transplantation 01/01/2020 - "First European Case of Simultaneous Liver and Pancreas Transplantation as Treatment of Wolcott-Rallison Syndrome in a Small Child."
4.	Liver Transplantation 03/01/2016 - "En bloc multiorgan transplant (liver, pancreas, and kidney) for acute liver and renal failure in a patient with Wolcott-Rallison syndrome."
5.	Kidney Transplantation 02/01/2015 - "Liver, pancreas and kidney transplantation for the treatment of Wolcott-Rallison syndrome."