Principal Investigator: John P. Loftus

Co-PI: Luis Pablo Macho

DESCRIPTION (provided by applicant): 

Hepatocutaneous syndrome (HCS) is a rare disease in dogs characterized by superficial necrolytic dermatitis (SND) skin lesions in conjunction with a characteristic hepatopathy. A unifying feature of HCS is hypoaminoacidemia, which is thought to provoke the characteristic skin lesions of this disease. Aminoaciduria has been recently identified as component of this syndrome. The two amino acids most substantially and consistently elevated in the urine were lysine (all dogs) and proline (variably). Diseases in human beings with renal losses of either amino acid have some features similar to HCS. These imply a specific amino acid transport defect central to the disease. Thus, genetic predisposition to disease that would have implications for rapid screening of dogs with liver abnormalities in the short-term and possible gene therapy targets in the long-term.

To enhance our understanding of HCS, it is essential to broaden investigation of this disease. Metabolomic profiling via mass spectrometry (GCTOF-MS) allows for rapid, efficient and economical assessment of changes in the metabolic profile of biological samples. We propose metabolic screening of patients with comparison to healthy control samples. This will identify important alterations in metabolic function in this disease, which are likely to ensue with lysinuria, such as carnitine deficiency. These data will enhance our understanding of the pathophysiology of HCS, with implications for identification of its pathogenesis. Identification of novel diagnostic and therapeutic targets would provide early diagnosis and additional treatments for a disease with a generally poor prognosis and often devastating implications for patient quality of life.