Analysis of ketogenic diet on developmental and epileptic encephalopathy caused by <i>PIGA</i> gene mutation_Journal of Epilepsy

Authors：

ZHANG Peiqi ,  LI Hua , GUO Jing , WANG Yao , PENG kai

Department of Epilepsy , Guangdong Sanjiu Brain Hospital , Guangzhou 510520, China;

Corresponding author：

LI Hua, Email: lihua1051@163.com

Keywords：

Ketogenic diet; Epilepsy; PIGA gene; Developmental and epileptic encephalopathy

DOI：

10.7507/2096-0247.202311015

Video：

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Objective To explore the efficacy of ketogenic diet on developmental and epileptic encephalopathy caused by PIGA gene mutation. Method A retrospective analysis was conducted on patients with developmental and epileptic encephalopathy admitted to Guangdong Sanjiu Brain Hospital from March 2016 to June 2020. Patients with positive PIGA gene mutations were selected, and their clinical characteristics and treatment effects were analyzed. Result A total of 6 epilepsy patients with positive PIGA gene mutations were collected, all of whom were male. 5 cases were heterozygous mutations originating from the mother, and 1 case was a new mutation. All 6 patients were accompanied by varying degrees of psychomotor developmental delay, various types of epileptic seizures, multifocal discharge on EEG, and varying degrees of brain hypoplasia indicated by cranial MRI. All 6 patients met the criteria for drug-resistant epilepsy and were recommended to undergo ketogenic diet treatment, but three patients were discontinued in the early stages. Among them, Case 3 experienced hyperlipidemia on the fifth day of ketogenic diet and was discontinued, while Case 5 experienced transient hypoglycemia on the second day and the family refused to use it. Case 6: After one week of ketogenic diet, the family members voluntarily stopped using it. Only three patients adhered to a long-term ketogenic diet for more than 2 years. The efficacy of ketogenic diet treatment in cases 1 and 4 was very significant, reaching a seizure free state. Case 2 showed a 50% reduction in seizure frequency after ketogenic diet treatment. Case 4 developed hyperlipidemia after two years of ketogenic diet, and after discontinuing the ketogenic diet for about two months, the blood lipids returned to normal. Comparing patients in the ketogenic group with those in the non ketogenic group, it was found that the ketogenic group had a clear therapeutic effect after treatment. Among them, two patients had no seizures for more than a year and showed significant progress in development compared to before. Two years after ketogenic diet treatment, the EEG showed a significant decrease or disappearance of epileptic discharge compared to before. Conclusion Patients with developmental latency caused by PIGA gene mutations have an early only age, diverse types of sizes, varying degrees of psychomotor developmental delay, and some are compatible by von as possible.

Citation： ZHANG Peiqi, LI Hua, GUO Jing, WANG Yao, PENG kai. Analysis of ketogenic diet on developmental and epileptic encephalopathy caused by PIGA gene mutation. Journal of Epilepsy, 2024, 10(1): 12-20. doi: 10.7507/2096-0247.202311015 Copy

1.	Raga S, Specchio N, Rheims S, et al. Developmental and epileptic encephalopathies: recognition and approaches to care. Epileptic Disord, 2021, 23(1): 40-52.
2.	Nieh SE, Sherr EH. Epileptic encephalopathies: new genes and new pathways. Neurotherapeutics, 2014, 11(4): 796-806.
3.	Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, et al. Ketogenic diet and epilepsy. Nutrients, 2019, 11(10): 2510.
4.	Sampaio LP. Ketogenic diet for epilepsy treatment. Arq Neuropsiquiatr, 2016, 74(10): 842-848.
5.	Wells J, Swaminathan A, Paseka J, et al. Efficacy and safety of a ketogenic diet in children and adolescents with refractory epilepsy-a review. Nutrients, 2020, 12(6): 1809.
6.	Kato M, Saitsu H, Murakami Y, et al. PIGA mutations cause early-onset epileptic encephalopathies and distinctive features. Neurology, 2014, 82(18): 1587-96.
7.	Johnston JJ, Gropman AL, Sapp JC, et al. The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria. Am J Hum Genet, 2012, 90(2): 295-300.
8.	Knaus A, Pantel JT, Pendziwiat M, et al. Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis. Genome Med, 2018, 10(1): 3.
9.	Kim YO, Yang JH, Park C, et al. A novel PIGA mutation in a family with X-linked, early-onset epileptic encephalopathy. Brain Dev, 2016, 38(8): 750-754.
10.	Tarailo-Graovac M, Sinclair G, Stockler-Ipsiroglu S, et al. The genotypic and phenotypic spectrum of PIGA deficiency. Orphanet J Rare Dis, 2015, 10: 23.
11.	Chiyonobu T, Inoue N, Morimoto M, Kinoshita T, Murakami Y. Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations in PIGW is associated with West syndrome and hyperphosphatasia with mental retardation syndrome. J Med Genet, 2014, 51(3): 203-207.
12.	Cabasson S, Van-Gils J, Villéga F, et al. Early-onset epileptic encephalopathy related to germline PIGA mutations: A series of 5 cases. Eur J Paediatr Neurol, 2020, 28: 214-220.
13.	Olson HE, Kelly M, LaCoursiere CM, et al. Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression. Ann Neurol, 2017, 81(3): 419-429.
14.	Neuhofer CM, Funke R, Wilken B, et al. A novel mutation in PIGA associated with multiple congenital anomalies-hypotonia-seizure syndrome 2 (mcahs2) in a boy with a combination of severe epilepsy and gingival hyperplasia. Mol Syndromol, 2020, 11(1): 30-37.
15.	Swoboda KJ, Margraf RL, Carey JC, et al. A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload. Am J Med Genet A, 2014, 164A(1): 17-28.
16.	Joshi C, Kolbe DL, Mansilla MA, Mason S, Smith RJ, Campbell CA. Ketogenic diet - a novel treatment for early epileptic encephalopathy due to PIGA deficiency. Brain Dev, 2016, 38(9): 848-851.

1. Raga S, Specchio N, Rheims S, et al. Developmental and epileptic encephalopathies: recognition and approaches to care. Epileptic Disord, 2021, 23(1): 40-52.
2. Nieh SE, Sherr EH. Epileptic encephalopathies: new genes and new pathways. Neurotherapeutics, 2014, 11(4): 796-806.
3. Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, et al. Ketogenic diet and epilepsy. Nutrients, 2019, 11(10): 2510.
4. Sampaio LP. Ketogenic diet for epilepsy treatment. Arq Neuropsiquiatr, 2016, 74(10): 842-848.
5. Wells J, Swaminathan A, Paseka J, et al. Efficacy and safety of a ketogenic diet in children and adolescents with refractory epilepsy-a review. Nutrients, 2020, 12(6): 1809.
6. Kato M, Saitsu H, Murakami Y, et al. PIGA mutations cause early-onset epileptic encephalopathies and distinctive features. Neurology, 2014, 82(18): 1587-96.
7. Johnston JJ, Gropman AL, Sapp JC, et al. The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria. Am J Hum Genet, 2012, 90(2): 295-300.
8. Knaus A, Pantel JT, Pendziwiat M, et al. Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis. Genome Med, 2018, 10(1): 3.
9. Kim YO, Yang JH, Park C, et al. A novel PIGA mutation in a family with X-linked, early-onset epileptic encephalopathy. Brain Dev, 2016, 38(8): 750-754.
10. Tarailo-Graovac M, Sinclair G, Stockler-Ipsiroglu S, et al. The genotypic and phenotypic spectrum of PIGA deficiency. Orphanet J Rare Dis, 2015, 10: 23.
11. Chiyonobu T, Inoue N, Morimoto M, Kinoshita T, Murakami Y. Glycosylphosphatidylinositol (GPI) anchor deficiency caused by mutations in PIGW is associated with West syndrome and hyperphosphatasia with mental retardation syndrome. J Med Genet, 2014, 51(3): 203-207.
12. Cabasson S, Van-Gils J, Villéga F, et al. Early-onset epileptic encephalopathy related to germline PIGA mutations: A series of 5 cases. Eur J Paediatr Neurol, 2020, 28: 214-220.
13. Olson HE, Kelly M, LaCoursiere CM, et al. Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression. Ann Neurol, 2017, 81(3): 419-429.
14. Neuhofer CM, Funke R, Wilken B, et al. A novel mutation in PIGA associated with multiple congenital anomalies-hypotonia-seizure syndrome 2 (mcahs2) in a boy with a combination of severe epilepsy and gingival hyperplasia. Mol Syndromol, 2020, 11(1): 30-37.
15. Swoboda KJ, Margraf RL, Carey JC, et al. A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: a neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload. Am J Med Genet A, 2014, 164A(1): 17-28.
16. Joshi C, Kolbe DL, Mansilla MA, Mason S, Smith RJ, Campbell CA. Ketogenic diet - a novel treatment for early epileptic encephalopathy due to PIGA deficiency. Brain Dev, 2016, 38(9): 848-851.

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