Defining the phenotype and diagnostic considerations in adults with congenital disorders of N-linked glycosylation

Abstract

Congenital disorders of N-glycosylation (CDG) form a rapidly growing group of more than 20 inborn errors of metabolism. Most patients are identified at the pediatric age with multisystem disease. There is no systematic review on the long-term outcome and clinical presentation in adult patients. Here, we review the adult phenotype in 78 CDG patients diagnosed with 18 different forms of N-glycosylation defects. Characteristics include intellectual disability, speech disorder and abnormal gait. After puberty, symptoms might remain non-progressive and patients may lead a socially functional life. Thrombosis and progressive symptoms, such as peripheral neuropathy, scoliosis and visual demise are specifically common in PMM2-CDG. Especially in adult patients, diagnostic glycosylation screening can be mildly abnormal or near-normal, hampering diagnosis. Features of adult CDG patients significantly differ from the pediatric phenotype. Non-syndromal intellectual disability, or congenital malformations in different types of CDG and decreasing sensitivity of screening might be responsible for the CDG cases remaining undiagnosed until adulthood.

Keywords::

• adult metabolic disease
• ataxia
• cataract
• CDG
• N-linked glycosylation
• scoliosis
• thrombosis

View correction statement:

Erratum

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Most patients with congenital disorders of N-glycosylation (CDG) with abnormal N-glycosylation are diagnosed in the pediatric age and a multisystem presentation.

• N-linked CDG leads to early death in about 25% of the patients.

• Most children with CDG without multisystem involvement reach adulthood.

• The common adult phenotype involves intellectual disability, speech disorder, visual loss, neuropathy and ataxia.

• Systemic involvement in adult includes scoliosis, cataract and episodes of venous thromboses.

• New types of CDGs have been defined in adults with isolated neurologic phenotype or intellectual disability.

• In adult patients, CDG screening can be near-normal, hampering the diagnosis.

• Due to congenital malformations, CDG cases might remain undiagnosed until adulthood.