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Use of ketogenic diet in MOGS-CDG: a case study 

Biochemical/Metabolic and Therapeutics
  • Primary Categories:
    • Metabolic Genetics
  • Secondary Categories:
    • Metabolic Genetics
Introduction
MOGS-CDG (CDG-IIb) is a rare congenital disorder of N-linked glycosylation characterized by hypotonia, seizures, hypogammaglobinemia, susceptibility to infections, developmental delay, hypoventilation, and dysmorphic facies. There are only approximately 24 known cases of MOGS-CDG in the literature and the often severe, multi-systemic manifestations of this condition make clinical management difficult. Here, we present a family with two affected siblings and a prior sibling who died at 19 months old due to suspected MOGS-CDG. Ketogenic diet has been trialed in a small set of CDG patients with severe CNS presentations with success. In one of these siblings who was experiencing intractable seizures, a low-ratio ketogenic diet was started with the goal of optimizing seizure control.  

Case Presentation
Patient 1 is a 19-month-old male diagnosed prenatally on amniocentesis with compound heterozygous variants in MOGS (c.1675c>T, p.S559P and c.311A>C, p.Y104S) of biparental inheritance after WGS in one of her previous affected children revealed the same variants. He is G-tube and ventilator dependent, has severe hypotonia, global developmental delay, epilepsy, anemia, without frequent infections, and has a Nijmegen pediatric CDG rating scale score of 31 (severe). Patient 2 is the 4-month-old female sibling of Patient 1 and was also diagnosed prenatally with the same compound heterozygous variants in MOGS as Patient 1. She is G-tube and ventilator dependent, has epilepsy, hypothyroidism, global developmental delay, hypotonia, pulmonary valve thickening, adrenal insufficiency, dysmorphic facies, has had multiple, severe bacterial infections, and a Nijmegen pediatric CDG rating scale score of 31 (severe).  

Diagnostic Workup
Diagnosis in MOGS-CDG is complicated by the fact that CDT testing is rarely positive in these patients, however, urine oligosaccharide testing is diagnostic in 100% of patients. In the case of our two patients, since familial pathogenic variants were already known, molecular testing was used first line for prenatal diagnosis. Both patients also had quantitative immunoglobulins sent which are non-diagnostic for both patients since they were drawn before 6 months of age. Patient 1 had urine oligosaccharides sent which revealed a profile consistent with his molecular diagnosis. 

Treatment and Management
Both of our patients are receiving therapies for their hypotonia and associated global developmental delay. Neither patient is currently on gammaglobulin. Both patients are currently on Keppra for seizure control and Patient 1 is additionally on Zonisade, Cannabidiol, and a ketogenic diet for seizure control. Patient 2 is also on phenobarbital for seizure control. 

Outcome and Follow-Up
After one month Patient 1 has obtained good seizure control since initiating the ketogenic diet and remains infection free. He has tolerated this diet well without episodes of hypoglycemia (patient’s mother monitors at home). Consistent ketosis has not been confirmed yet as family has not started regular urine ketone monitoring.

 

Discussion
Ketogenic diets are well known for their utility as adjuvant treatment for patients with intractable seizures. Thus far their implementation in patients with rare CDG’s has been very limited. One reason for this is that ketogenic diets have been known to cause hypoglycemia in CDG’s and require some degree of caution. An additional reason clinicians are cautious to start ketogenic diets in CDG’s are unpublished reports of increased infection frequency. 

 

Conclusion
The broad utility of ketogenic diets for seizure control across the spectrum of CDG’s remain uncertain. Given that CDG’s represent such a heterogeneous collection of individually rare diseases, further studies are needed on specific CDG’s to better evaluate the safety and efficacy of this diet. Our short-term follow-up of one patient with MOGS-CDG shows that he has tolerated this diet well from a metabolic standpoint and has not had any infections. This is particularly interesting given the propensity of MOGS-CDG patients to acquire severe bacterial and viral infections. Further follow-up will be crucial to confirm these findings.  

 

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