Dolichol kinase deficiency

Dolichol kinase deficiency is a rare genetic disorder that affects the synthesis of glycoproteins in the body. This condition is caused by mutations in the DOLK gene, which encodes the enzyme dolichol kinase. Dolichol kinase is essential for the production of dolichol phosphate, a molecule that plays a critical role in the N-glycosylation process, a type of post-translational modification of proteins. The deficiency in dolichol kinase activity leads to a disruption in the N-glycosylation pathway, resulting in the accumulation of incomplete glycoproteins. This accumulation can cause a wide range of symptoms and lead to various health problems.

Symptoms and Diagnosis

The symptoms of dolichol kinase deficiency can vary widely among affected individuals but often include developmental delay, intellectual disability, epilepsy, and abnormalities in muscle tone such as hypotonia (decreased muscle tone) or hypertonia (increased muscle tone). Some patients may also exhibit microcephaly (a smaller than normal head size), visual impairment, and hearing loss. Due to the broad spectrum of symptoms, the diagnosis of dolichol kinase deficiency can be challenging and is often based on a combination of clinical evaluation, biochemical tests, and genetic testing to identify mutations in the DOLK gene.

Genetics

Dolichol kinase deficiency is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. Parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not show signs and symptoms of the condition.

Treatment and Management

As of now, there is no cure for dolichol kinase deficiency, and treatment is primarily supportive and symptomatic. Management strategies may include antiepileptic medications to control seizures, physical therapy to improve muscle tone and mobility, and specialized care to address intellectual disability and sensory impairments. Early intervention and a multidisciplinary approach are crucial to improving the quality of life for individuals with this condition.

Research and Outlook

Research on dolichol kinase deficiency is ongoing, with scientists exploring the molecular mechanisms underlying the disorder and investigating potential therapeutic strategies. Advances in genetic research and therapy hold promise for future treatments that can target the root cause of the condition.

NIH genetic and rare disease info

• NIH info on Dolichol kinase deficiency

Dolichol kinase deficiency is a rare disease.