Warburg Micro syndrome
| Warburg Micro syndrome | |
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| Other names: Hereditary Spastic Paraplegia 69, RAB18 Associated Hereditary Spastic Paraplegia, SPG69,[1] RAB 18 Deficiency [2] | |
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| a) Pedigree b) children illustrating severe dystrophy, microcephaly, and distal contractures c)severe osteopenia on conventional X-rays d-g) parietal pachygyria h)mutations in the RAB3GAP1 gene in people with WARBM1 | |
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| Symptoms | congenital cataract, progressive spasticity, intellectual or developmental disability, weak core, nonverbal or limited speech, small head, small eyes, optic atrophy, and hypogenitalism [3] |
| Usual onset | cataracts appear at birth, delayed milestones evident by 4-6 months [3] |
| Diagnostic method | symptom based, genetic testing [3] |
| Treatment | Supportive care[3] |
| Frequency | 144 cases reported in literature [4] |
Warburg Micro syndrome (WARBM), also known as Spastic Paraplegia 69 (SPG69) or RAB18 Deficiency, is a rare autosomal recessive genetic disorder characterized by congenital cataract, hypotonia, spastic diplegia, intellectual or developmental disability, microcephaly, microcornea, optic atrophy, and hypogenitalism.[5]
Signs and symptoms
The clinical presentation of Warburg Micro syndrome is consistent with:[6]
- Microcephaly
- Microphthalmia
- Microcornea
- Congenital cataracts
- Corpus callosum hypoplasia
- Hypogonadism
Genetics
Warburg Micro is autosomal recessive, which means two copies of an abnormal gene must be present for the disorder to appear. Warburg Micro is caused by mutations in any of the following genes: RAB18, RAB3GAP1, RAB3GAP2 and TBC1D20 [7]
Diagnosis
Warburg Micro syndrome is diagnosed by genetic testing. It should be suspected when cataracts are present at birth and developmental delays are noted.[3]
Treatment
There is no specific treatment for Warburg Micro syndrome, but there are ways to help the symptoms that come with it. Congenital cataracts should be operated in the first two months. Physical and occupational therapy should begin as soon as possible. Medication can treat seizures, spasticity, and digestive issues. Orthotics like braces and assistive devices like standers and wheel chairs can improve bone health, spasticity, and mobility. Specialists can perform surgeries to address hip and spine health. Therapeutics trials in other forms of early onset hereditary spastic paraplegia are ongoing and include cholesterol lowering drugs, antioxidants, potassium channel blockers, MGLL inhibitors among others. More understanding of the overlapping mechanisms of these disorders and Warburg Micro is required to understand whether they may some day be applicable in SPG 69. [8]
References
- ↑ Hereditary spastic paraplegia. PP Liberski, C Blackstone - Neurodegeneration, 2017
- ↑ Handley M, Sheridan E. RAB18 Deficiency. In: GeneReviews®. University of Washington, Seattle, Seattle (WA); 1993. PMID 29300443
- ↑ 3.0 3.1 3.2 3.3 3.4 "Warburg Micro Syndrome". Archived from the original on 2022-03-08. Retrieved 2022-04-17.
- ↑ Handley, Mark T.; et al. (2013). "Mutation Spectrum inRAB3GAP1,RAB3GAP2, andRAB18and Genotype-Phenotype Correlations in Warburg Micro Syndrome and Martsolf Syndrome". Human Mutation. 34 (5): 686–696. doi:10.1002/humu.22296. PMID 23420520. S2CID 2437070. Archived from the original on 2022-03-27. Retrieved 2022-04-17.
- ↑ "WARBURG Micro Syndrome." https://www.ncbi.nlm.nih.gov/ Archived 2017-12-29 at the Wayback Machine 10 Mar. 2008 <https://www.ncbi.nlm.nih.gov/omim/?term=600118 Archived 2022-07-02 at the Wayback Machine>.
- ↑ "Warburg Micro Syndrome". NORD (National Organization for Rare Disorders). Archived from the original on 8 March 2022. Retrieved 28 June 2022.
- ↑ Handley, Mark T.; Carpanini, Sarah M.; Mali, Girish R.; Sidjanin, Duska J.; Aligianis, Irene A.; Jackson, Ian J.; Fitzpatrick, David R. (2015). "Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation". Open Biology. 5 (6): 150047. doi:10.1098/rsob.150047. PMC 4632505. PMID 26063829.
- ↑ "Are There Treatments for Warburg Micro." https://www.warburgmicro.org/treatment/ Archived 2022-04-03 at the Wayback Machine 27 Mar. 2022.
External links
- Warburg Micro Research Foundation Info on Warburg Micro Syndrome Archived 2021-12-30 at the Wayback Machine
- Patient Registry at CoRDS Archived 2022-03-27 at the Wayback Machine
- Spastic Paraplegia Foundation [1] Archived 2022-04-18 at the Wayback Machine
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