congenital disorder of glycosylation type 1EE with or without immunodeficiency

Congenital disorder of glycosylation type 1EE with or without immunodeficiency is a multisystem condition that affects both neurological and immune functions, among other systems. Pathogenic variants in the MAN2B2 gene, which plays a role in glycosylation processes, underlie the condition. Affected individuals typically present in infancy with symptoms such as poor head control, muscle hypotonia, and recurrent infections. Because precise prevalence data are not available, the condition is understood to be very rare, and presentations can vary in severity.

The clinical presentation of this condition is marked by a constellation of features affecting multiple organ systems. Neurologically, affected individuals exhibit poor head control, hypotonia, seizures, microcephaly, strabismus, and delayed ability to crawl, indicating central nervous system involvement. The immune system is also compromised, as evidenced by decreased circulating IgG, a reduced total lymphocyte count, an inverted CD4:CD8 ratio, decreased proportions of naive T cells, increased circulating IgE, recurrent oral herpes, chronic oral candidiasis, and reduced antigen-specific T cell proliferation. In addition, other systems can be affected, with hepatomegaly, thromboembolic stroke, hip osteoarthritis, inguinal hernia, chronic diarrhea, short stature, short chin, and hypertelorism being consistently reported. Not all individuals experience every feature to the same degree, and severity varies considerably.

The condition is caused by pathogenic variants in the MAN2B2 gene, which is involved in essential glycosylation processes that affect various cellular functions. It is inherited in an autosomal recessive pattern, meaning that an individual must receive a mutated copy of the gene from each parent to be affected. This inheritance pattern implies that both parents are typically asymptomatic carriers, and there is a 25% chance with each pregnancy for the child to be affected. Genetic counseling can help families understand the implications of this inheritance pattern and explore options for family planning.

Currently, management focuses on supportive care and tailored symptom management as there are no FDA-approved treatments for this condition. A multidisciplinary team is essential to address the complex needs of affected individuals; this may include specialists in neurology, immunology, gastroenterology, and other fields as needed. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. In addition, genetic counseling is recommended to guide families regarding treatment options and family planning.

Outcomes for individuals with congenital disorder of glycosylation type 1EE are highly variable and depend on the severity of the symptoms and access to multidisciplinary care. With current standards of care, many affected individuals benefit from periods of stabilization following early developmental challenges, although complications affecting both neurological and immunological function may persist. Outcomes described in medical literature continue to evolve as standards of care improve, and variability in disease progression is common. Families are encouraged to seek support from specialists and genetic counselors to navigate the evolving clinical landscape.