congenital disorder of glycosylation, type 1DD

Congenital disorder of glycosylation, type 1DD is a multisystem condition that affects several body systems including the central nervous system and other organs. It is associated with a variant in the DHRSX gene, although the precise molecular mechanism remains to be fully defined. Affected individuals typically present in infancy, with signs such as failure to thrive and feeding difficulties. As precise prevalence estimates are not well established, the condition is understood to be very rare.

The clinical presentation of this condition is marked by several characteristic findings. Nearly all affected children experience failure to thrive, axial hypotonia, and require gastrostomy tube feeding in infancy, along with a distinct abnormal facial shape. Central nervous system involvement is evident with severe global developmental delay and profound intellectual disability, reflecting cognitive and neurological challenges. Other common features include corneal erosion and sensorineural hearing impairment, while additional issues such as scoliosis, hepatomegaly, gastroesophageal reflux, apnea, stridor, and seizures occur in a subset of individuals. Not all individuals experience all features, and severity varies considerably.

This condition is linked to changes in the DHRSX gene. Although detailed information on the gene’s normal function and the exact molecular mechanism is not available, disruption of DHRSX is believed to interfere with normal glycosylation processes. Inheritance details are not specified, and as such, the genetic transmission pattern remains unclear. Families are encouraged to seek genetic counseling for clarification and further discussion of potential familial implications.

Currently, management focuses on supportive care and symptom management, with treatment plans tailored to the specific needs of the individual. A multidisciplinary team approach is important, with specialists addressing issues such as feeding challenges, developmental delays, and respiratory or cardiac concerns that may arise. Long-term management includes regular surveillance to identify complications early, which may involve monitoring of growth, neurological development, and musculoskeletal issues such as scoliosis. Patients should discuss treatment options with their healthcare team to determine which therapies may be appropriate for their specific situation, and genetic counseling is recommended for families.

The condition is lifelong and characterized by significant neurodevelopmental challenges, with early presentation and severe impacts on cognitive function. Outcomes vary widely between individuals, and while affected children experience major developmental delays, the overall course may include periods of relative stabilization with appropriate supportive care. With current standards of care, many individuals benefit from advances in multidisciplinary management, and outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with congenital disorders and to seek genetic counseling for ongoing guidance.