Wolcott–Rallison syndrome

Wolcott–Rallison syndrome
Synonyms	Early-onset diabetes mellitus with multiple epiphyseal dysplasia
Pronounce	N/A
Field	Pediatrics, Endocrinology, Medical genetics
Symptoms	Diabetes mellitus, epiphyseal dysplasia, osteopenia, developmental delay, hepatic failure, renal failure
Complications	Multisystem organ failure, intellectual disability
Onset	Infancy
Duration	Lifelong
Types	N/A
Causes	Autosomal recessive mutations in the EIF2AK3 gene
Risks	Consanguinity
Diagnosis	Genetic testing, clinical evaluation
Differential diagnosis	Neonatal diabetes, Fanconi syndrome, other syndromic forms of diabetes
Prevention	Genetic counseling
Treatment	Insulin therapy, supportive care for organ dysfunction
Medication	Insulin, levothyroxine (if hypothyroidism is present)
Prognosis	Guarded; depends on severity of organ involvement
Frequency	Very rare
Deaths	N/A

Wolcott–Rallison syndrome, WRS, 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.

Genetics

The main focus for this autosomal recessive disease is mutations to the EIF2AK3 gene. This gene is located on chromosome 2 p11.2. For some cases for unrelated families, identical mutations were observed, although these cases are rare.

The EIKF2AK3 gene codes for PERK (pancreatic endoplasmic reticulum kinase), an explanation for the spectrum symptoms. PERK is associated with the activity of beta cells in the pancreas. Beta cells are needed for the proper release of insulin into the blood stream after an increase in blood glucose. The endoplasmic reticulum is a major protein sorting and processing center in every cell of the body. A broad range of bodily systems is affected because of the lack of post-translational modifications of to proteins. These proteins are coming from the endoplasmic reticulum can be in the cells of the various organ systems effected, such as urinary and central nervous system. EIKF2AK3 is also involved in bone cells. This is part of the reason why patients suffer from multiple epiphyseal dysplasia and osteopenia.

Diagnosis

Initially, patients with neonatal or early-childhood onset diabetes are possible candidates for having Wolcott–Rallison syndrome. The other symptoms include the multiple epiphyseal dysplasia, osteopenia, intellectual disability, and hepatic and renal dysfunction.Hypothyroidism is rare is WRS patients but can occur.

Therapies

The most common method to manage hypoglycemia and diabetes is with an insulin pump. If needed, the patient can undergo thyroxin therapy in order to maintain proper thyroid stimulating hormone levels. This has only been needed in a few cases were hypothyroidism was present in the patient.