Wolcott–Rallison syndrome: Difference between revisions

From WikiMD's Medical Encyclopedia

← Older edit
CSV import
No edit summary
 
Line 1: Line 1:
{{Infobox medical condition (new)
{{Infobox medical condition (new) | name = Wolcott–Rallison syndrome | synonyms = Early-onset diabetes mellitus with multiple epiphyseal dysplasia | image = Walcott-Rallison Syndrome.png | alt = | caption = Radiograph of a WRS child presenting with dysplastic bone growth in various regions of the body. | 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 | causes = [[Autosomal recessive]] mutations in the [[EIF2AK3]] gene | risks = [[Consanguinity]] | diagnosis = [[Genetic testing]], clinical evaluation | differential = [[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 }}
| synonyms       = Early-onset diabetes mellitus with multiple epiphyseal dysplasia
'''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 failure|hepatic]] and [[renal failure|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.
| name            = Wolcott–Rallison syndrome
| image           = Walcott-Rallison Syndrome.png
| alt             =  
| caption         = Radiograph of a WRS child presenting with dysplastic bone growth in various regions of the body.
| pronounce      =
| field           =  
| geneReviewsID  =
| symptoms       =  
| complications   =  
| onset           =  
| duration       =
| types          =  
| causes         =  
| risks           =  
| diagnosis       =  
| differential   =  
| prevention     =  
| treatment       =  
| medication     =  
| prognosis       =  
| frequency       =  
| deaths          =
}}
'''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 failure|hepatic]] and [[renal failure|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.<ref name="pmid18500571">{{cite journal | vauthors = Søvik O, Njølstad PR, Jellum E, Molven A | title = Wolcott-Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome | journal = Journal of Inherited Metabolic Disease | volume = 31 Suppl 2 | issue =  | pages = S293-7 | date = December 2008 | pmid = 18500571 | doi = 10.1007/s10545-008-0866-1 }}</ref>
<ref name="pmid16813601">{{cite journal | vauthors = Durocher F, Faure R, Labrie Y, Pelletier L, Bouchard I, Laframboise R | title = A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott-Rallison syndrome | journal = Clinical Genetics | volume = 70 | issue = 1 | pages = 34–8 | date = July 2006 | pmid = 16813601 | doi = 10.1111/j.1399-0004.2006.00632.x }}</ref> Other disease names include multiple epiphyseal dysplasia and early-onset diabetes mellitus.<ref name=":0" /> Most patients do not survive to adult hood with this disease.<ref name=":1" /> The majority of these WRS patients die from [[Hepatitis|fulminant hepatitis]] during childhood.<ref name=":02" /> There are few reported cases for this disease. Of the 54 families worldwide with reported cases of WRS, 22.2% of them are from the Kingdom of [[Saudi Arabia]].<ref name=":02">{{cite journal | vauthors = Habeb AM | title = Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review | journal = The Libyan Journal of Medicine | volume = 8 | pages = 21137 | date = June 2013 | pmid = 23759358 | pmc = 3679509 | doi = 10.3402/ljm.v8i0.21137 }}</ref> Of the 23 WRS patients in Saudi Arabia, all but one is the result of [[Consanguinity|consanguineous]] marriages.<ref name=":02" />  Another country where WRS cases have been found is [[Kosovo]]. Here, the Albanian population is also known for consanguineous marriages, but there were some cases involving patients from non-consanguineous parents that were carriers for the same mutant allele.<ref name=":1" />


==Genetics==
==Genetics==
The main focus for this autosomal recessive disease is mutations to the EIF2AK3 gene. This gene is located on [[chromosome 2]] p11.2.<ref name=":0">{{cite web|last1=McKusick|first1=Victor|title=Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes|url=http://www.omim.org/entry/226980?search=226980&highlight=226980|website=Online Mendelian Inheritance in Man|publisher=Johns Hopkins University|access-date=14 October 2015}}</ref> In unrelated families, different mutations have been observed in the EIF2AK3 gene, including missense and nonsense mutations.<ref name=":0"/> For some cases for unrelated families, identical [[mutation]]s were observed, although these cases are rare.
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 [[mutation]]s 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 cell]]s in the pancreas. Beta cells are needed for the proper release of insulin into the blood stream after an increase in blood glucose.<ref name=":1">{{cite journal | vauthors = Spehar Uroić A, Mulliqi Kotori V, Rojnić Putarek N, Kušec V, Dumić M | title = Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome | journal = European Journal of Pediatrics | volume = 173 | issue = 4 | pages = 529–31 | date = April 2014 | pmid = 24194294 | doi = 10.1007/s00431-013-2189-y }}</ref> This [[kinase]] is needed for the control of protein levels in the [[endoplasmic reticulum]] and is linked to [[ribosome]] activity.<ref>{{cite journal | vauthors = Porter JR, Barrett TG | title = Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and beta cell failure | journal = Journal of Medical Genetics | volume = 42 | issue = 12 | pages = 893–902 | date = December 2005 | pmid = 15772126 | pmc = 1735963 | doi = 10.1136/jmg.2005.030791 }}</ref> 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 modification]]s 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.<ref name=":1" /> This is part of the reason why patients suffer from [[multiple epiphyseal dysplasia]] and [[osteopenia]].
The EIKF2AK3 gene codes for PERK (pancreatic endoplasmic reticulum kinase), an explanation for the spectrum symptoms. PERK is associated with the activity of [[beta cell]]s 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 modification]]s 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==
== Diagnosis==
Initially, patients with neonatal or early-childhood onset diabetes are possible candidates for having Wolcott–Rallison syndrome.<ref name="pmid18500571" /> The other symptoms include the [[multiple epiphyseal dysplasia]], [[osteopenia]], [[intellectual disability]], and [[Hepatic dysfunction|hepatic]] and [[Renal failure|renal dysfunction]].<ref name="pmid18500571" /> Patients with the symptoms that line up with Wolcott–Rallison syndrome can be suggested for genetics testing. The key way to test for this disease specifically is through genetic testing for the EIKF2AK3 mutation.<ref>{{cite journal | vauthors = Senée V, Vattem KM, Delépine M, Rainbow LA, Haton C, Lecoq A, Shaw NJ, Robert JJ, Rooman R, Diatloff-Zito C, Michaud JL, Bin-Abbas B, Taha D, Zabel B, Franceschini P, Topaloglu AK, Lathrop GM, Barrett TG, Nicolino M, Wek RC, Julier C | title = Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity | journal = Diabetes | volume = 53 | issue = 7 | pages = 1876–83 | date = July 2004 | pmid = 15220213 | doi = 10.2337/diabetes.53.7.1876 }}</ref> Molecular genetic analysis can be done for the patient and the parents to test for de novo mutations or inherited. It can also show whether the patient's parents are heterozygotes or homozygotes for the normal phenotype.<ref name=":1" /> [[X-ray|X-Rays]] can show bone age in relation to actual age. Typically the bond age is a few years less than the actual in the patients with WRS.<ref name=":1" /><ref name=":02" /><ref>{{cite journal | vauthors = Hawkes CP, McGlacken-Byrne SM, Murphy NP | title = Short stature in child with early-onset diabetes | journal = European Journal of Pediatrics | volume = 172 | issue = 9 | pages = 1255–7 | date = September 2013 | pmid = 23644647 | doi = 10.1007/s00431-013-2007-6 }}</ref><ref name=":2" /> [[Hypothyroidism]] is rare is WRS patients but can occur.<ref name=":1" />
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 dysfunction|hepatic]] and [[Renal failure|renal dysfunction]].[[Hypothyroidism]] is rare is WRS patients but can occur.


==Therapies==
==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.
The most common method to manage [[hypoglycemia]] and [[diabetes]] is with an [[insulin pump]].<ref name=":2">{{cite journal | vauthors = Julier C, Nicolino M | title = Wolcott-Rallison syndrome | journal = Orphanet Journal of Rare Diseases | volume = 5 | issue = 1 | pages = 29 | date = November 2010 | pmid = 21050479 | pmc = 2991281 | doi = 10.1186/1750-1172-5-29 }}</ref> . However in infants and very young children long acting insulins like Glargine and Levemir are preferred to prevent recurrent hypoglycemia <ref>Sreeramaneni, Poorna Gopal Azad., & Ambula, S. R. V. (2017). Ketoacidosis in Neonatal Diabetes Mellitus, Part of Wolcott-Rallison Syndrome. The American Journal of Case Reports, 18, 719–722. http://www.amjcaserep.com/abstract/index/idArt/902804</ref>. As soon as parent knows Walcott-Rallison  syndrome is the source, treatment or therapy plans need to be drawn up along with frequent check ins to make sure kidney and liver functions are around normal and insulin therapy are working.<ref name=":1" /> 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.<ref name=":1" />
 
== References ==
<references />
== External links ==
*{{Commonscatinline}}
 
{{Medical resources
|  DiseasesDB      =
|  ICD10          = E13
|  ICD9            =
|  ICDO            =
|  OMIM            = 226980
|  MedlinePlus    =
|  eMedicineSubj  =
|  eMedicineTopic  =
|  MeshID          = C536739
|  GeneReviewsName =
|  Orphanet        = 1667
}}


{{DEFAULTSORT:Wolcott-Rallison syndrome}}
{{DEFAULTSORT:Wolcott-Rallison syndrome}}
Line 63: Line 18:
[[Category:Autosomal recessive disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Syndromes]]
[[Category:Syndromes]]
<gallery>
{{nt}}
File:Walcott-Rallison_Syndrome.png
</gallery>

Latest revision as of 04:34, 30 March 2025

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[edit]

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[edit]

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[edit]

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.

Retrieved from "https://wikimd.org/index.php?title=Wolcott–Rallison_syndrome&oldid=6540147"