About UGDH syndrome
At a glance
UGDH syndrome, also known as Jamuar syndrome or DEE84, is an ultra-rare metabolic disorder. The condition is caused by mutations in the UGDH gene, resulting in the absence or insufficient production of essential substances in the body. This primarily affects brain development and brain function and can lead to severe neurological impairments.
The role of UGDH
The UGDH gene contains the instructions for producing the enzyme UDP-glucose dehydrogenase (UGDH). This enzyme plays a crucial role in the production of specific sugar molecules that are essential for the formation and structural integrity of the extracellular matrix in the brain—the supportive framework surrounding brain cells. These molecules are also important for proper communication between nerve cells.
When mutations impair the function of the enzyme, these sugar molecules are not produced in sufficient amounts, disrupting these critical processes. As a result, abnormalities can arise in both brain development and brain function.
Clinical features
The symptoms and their severity vary from patient to patient. Most affected children experience severe epilepsy that is difficult to control with medication. Significant developmental delay is also common. Many children do not achieve independent sitting, walking, or speech. Additional features may include low muscle tone (hypotonia), cognitive disability, and feeding difficulties. In some patients, structural abnormalities of the brain have been identified.
Prevalence
UGDH syndrome was first described in 2020 (PMID: 32001716). Since then, fewer than one hundred patients have been reported worldwide. The actual number is likely higher, as the disorder was only recently identified, its clinical features overlap with those of other genetic and metabolic conditions, and diagnosis currently requires comprehensive genetic testing.
Treatment
Unfortunately, there is currently no treatment that addresses the underlying cause of UGDH syndrome. Medical care therefore focuses on symptom management and developmental support. Children may receive therapies such as physiotherapy, speech and language therapy, and occupational therapy to help them achieve their full potential and improve their quality of life.
References
Hengel, Holger et al. “Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.” Nature communications vol. 11,1 595. 30 Jan. 2020, doi:10.1038/s41467-020-14360-7