Congenital disorder of glycosylation type IIb in an infant with developmental and epileptic encephalopathy

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Congenital disorders of glycosylation (CDG) are a group of rare inherited metabolic diseases affecting protein and lipid glycosylation.
• CDG type IIb, specifically linked to MOGS gene mutations, presents with complex multisystemic symptoms, including neurological and developmental issues.
• Early diagnosis and intervention are crucial for managing CDG, but recognition can be challenging due to overlapping symptoms with other conditions.

Purpose of the Study:

• To report a case of a term infant with severe early-onset neurological and multisystemic symptoms.
• To identify the genetic cause of the infant's condition using whole exome sequencing.
• To evaluate the therapeutic effect of a mannose-based diet in managing the identified genetic disorder.

Main Methods:

• Clinical evaluation of a term infant presenting with progressive developmental delay, seizures, feeding difficulties, and failure to thrive.
• Comprehensive investigations including MRI, ruling out infections, metabolic acidosis, and structural brain malformations.
• Whole exome sequencing to identify the causative genetic mutation.

Main Results:

• The infant exhibited severe neonatal symptoms including vomiting, lethargy, seizures, neurological deterioration, hepatomegaly, nephromegaly, hypothyroidism, and auditory neuropathy.
• MRI revealed cerebral atrophy and dilated ventricles.
• Whole exome sequencing identified a homozygous missense mutation in the MOGS gene (c.2090T>C; p.Leu697Ser), confirming MOGS-CDG (CDG type IIb). A mannose-based diet resulted in partial clinical improvement.

Conclusions:

• This case underscores the importance of considering neurometabolic disorders like MOGS-CDG in infants with early-onset epileptic encephalopathy and multisystem involvement.
• Early genetic diagnosis through whole exome sequencing is critical for identifying MOGS-CDG.
• Supportive multidisciplinary care and potentially targeted dietary interventions, such as a mannose-based diet, can help improve outcomes and guide family counseling.