Wolcott–Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome

  title={Wolcott–Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome},
  author={Oddmund S{\o}vik and P{\aa}l Rasmus Nj{\o}lstad and Egil Jellum and Anders Molven},
  journal={Journal of Inherited Metabolic Disease},
SummaryWolcott-Rallison syndrome (WRS) (OMIM 226980) is a rare, autosomal recessive disorder with infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, osteopenia, mental retardation or developmental delay, and hepatic and renal dysfunction as main clinical findings. Patients with WRS have mutations in the EIF2AK3 gene, which encodes the pancreatic eukaryotic translation initiation factor 2-alpha kinase 3. We report a female patient who developed insulin-requiring diabetes at 2.5… 

Microscopic and ultrastructural features in Wolcott–Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases

Wolcott–Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by the association of permanent neonatal or early‐infancy insulin‐dependent diabetes, multiple bone dysplasia,

Frequency and spectrum of Wolcott–Rallison syndrome in Saudi Arabia: a systematic review

  • A. Habeb
  • Medicine
    The Libyan journal of medicine
  • 2013
Establishing a national or international registry for WRS would provide more reliable data on this rare condition and indicate that KSA has the largest collection of patients with WRS worldwide, and nine of the identifiable EIF2AK3 mutations appear to be confined to Arabs.

Two novel mutations in the EIF2AK3 gene in children with Wolcott–Rallison syndrome

Two novel mutations in the EIF2AK3 gene in children with Wolcott–Rallison syndrome are identified.

Wolcott–Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature *

The Wolcott–Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature.

Update in neonatal diabetes

Context is given to new data on neonatal diabetes mellitus, a rare group of insulin-requiring monogenic forms of diabetes presenting at birth or shortly thereafter, to give context to genetic studies critical in the diagnosis and treatment of these patients.

Pediatric hypoglycemia.

Coordinating Mitochondrial Biology Through the Stress-Responsive Regulation of Mitochondrial Proteases.

Identification of Novel Mutation in EIF2AK3 Gene as a Causal Variant in a Family With Rare Disease

Sequencing analysis of the EIF2AK3 gene in an Iranian girl suspicious for Wolcott-Rallison syndrome identified a homozygous novel non-sense mutation in exon 9 of the gene, Y479X.



Autopsy findings in the Wolcott-Rallison syndrome.

  • C. ThorntonD. J. CarsonF. Stewart
  • Medicine
    Pediatric pathology & laboratory medicine : journal of the Society for Pediatric Pathology, affiliated with the International Paediatric Pathology Association
  • 1997
An affected girl who died at the age of 4 years and on whom a full autopsy was performed, had mental retardation and recurrent episodes of self-limiting hepatic failure and had a deletion at 15q11-12 in 65% of her cells.

Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene.

It is demonstrated that EIF2AK3 kinase activity is essential for pancreas islet function and bone development in humans, and EIF 2AK3 as a possible target for therapeutic intervention in diabetes is suggested.

Wolcott-Rallison syndrome: pathogenic insights into neonatal diabetes from new mutation and expression studies of EIF2AK3

New features of the expression pattern of human EIF2AK3 that offer possible explanations for important clinical features ofThe Wolcott-Rallison syndrome that are not apparent in the transgenic mouse models are demonstrated.

Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity.

The patient with no EIF2AK3 involvement did not have any of the other variable clinical manifestations associated with WRS, which supports the idea that the genetic heterogeneity between this variant form of WRS and EIF 2AK3 WRS correlates with some clinical heterogeneity.

Marked elevation of urinary 3-hydroxydecanedioic acid in a malnourished infant with glycogen storage disease, mimicking long-chainl-3-hydroxyacyl-CoA dehydrogenase deficiency

SummaryAn infant with glycogen storage disease and prolonged malnourishment showed a urinary organic acid profile during an episode of fasting hypoglycaemia with inappropriate hypoketotic

Wolcott‐Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature

A novel 4‐base pair deletion is identified in exon 13, which results in a frameshift and premature stop codon, causing premature truncation of the protein and abolition of the carboxy‐ segment of the catalytic domain in Wolcott‐Rallison syndrome.

Secondary 3-hydroxydicarboxylic aciduria mimicking long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

The clinical features of L-CHAD deficiency include acute fasting intolerance with a Reye syndrome-like illness and a chronic course of skeletal and cardiac muscle myopathy, hepatic cirrhosis, peripheral neuropathy and in one case pigmentary retinopathy.

Hypoketonuric 3-hydroxydicarboxylic aciduria in five patients with glycogen storage disease

Five additional patients with glycogen storage diseases who, when hypoglycaemic, excreted excessive amounts of C 12 3-hydroxy-dicarboxylic acids suggestive of a long-chain fatty acid oxidation defect are reported on.

Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to β‐subunit mutations

The predominance of missense mutations and the milder myopathic phenotype are consistent, and the mutation localization within the protein correlates with the clinical phenotype, based upon homology to yeast thiolase.

Wolcott‐Rallison syndrome associated with congenital malformations and a mosaic deletion 15q 11–12

An affected girl who had recurrent episodes of hepatic failure for which no obvious cause was found is described and abnormal pancreatic histology and congenital abnormalities of the central nervous and cardio‐respiratory systems are revealed.