Dr. Huizing investigates rare human genetic disorders and associated intracellular processes in order to gain insight into the changes in molecular function that underlie various genetic metabolic disorders, with the hope of developing treatments for these illnesses. Her research focuses on disorders of sialic acid metabolism and of lysosome-related organelles.

Dr. Huizing also studies other sialic acid-related diseases, including sialuria, a progressive disease in which patients produce excess sialic acid. Symptoms can include developmental delay, coarse features, and liver enlargement. Sialuria appears to be due to a single mutation that causes a change in the three-dimensional structure of the active site of the UDP-GlcNAc 2-epimerase/ManNAc kinase enzyme. Dr. Huizing demonstrated that elimination of the single mutant allele using a synthetic small interfering RNA (siRNA) rescued the abnormal phenotype in cultured cells from sialuria patients. In ISSD and Salla disease, other sialic acid-related conditions, a transport malfunction causes sialic acid to accumulate in lysosomes. Dr. Huizing is evaluating possible steps to alleviate this sialic acid accumulation in cultured cells from ISSD and Salla patients.

Dr. Huizing is also investigating the causes of and potential treatments for disorders of lysosome-related organelles (LROs), including Hermansky-Pudlak syndrome (HPS), Chediak-Higashi syndrome, and Griscelli syndrome. A rare inherited disorder that has been identified in about 400 people worldwide, HPS is mainly characterized by decreased pigmentation (ocular or cutaneous albinism) and a lack of platelet dense bodies that causes bleeding problems. The disease can lead to prolonged bleeding and poor function of the lungs and intestine; fatal pulmonary fibrosis is a possible complication. An ongoing clinical trial at NHGRI is testing the drug pirfenidone as a potential HPS treatment for symptoms associated with pulmonary fibrosis.