HARP syndrome

HARP syndrome is an extremely rare neurodegenerative disorder whose name is an acronym for its cardinal features: Hypoprebetalipoproteinemia, Acanthocytosis, Retinitis pigmentosa, and Pallidal degeneration. The condition primarily affects the nervous system, the eyes, and lipid metabolism. It is now widely considered to be part of the spectrum of pantothenate kinase-associated neurodegeneration (PKAN), also known as neurodegeneration with brain iron accumulation type 1 (NBIA1), caused by mutations in the PANK2 gene. Both conditions share the hallmark finding of iron accumulation in the globus pallidus of the brain, often visible on MRI as the characteristic 'eye-of-the-tiger' sign. Clinically, patients with HARP syndrome present with progressive movement difficulties including dystonia and other extrapyramidal signs related to pallidal degeneration. Retinitis pigmentosa leads to progressive visual impairment, often beginning with night blindness and loss of peripheral vision. Acanthocytosis refers to the presence of abnormally shaped (spiculated) red blood cells in the peripheral blood, and hypoprebetalipoproteinemia denotes reduced levels of prebeta-lipoproteins (very low-density lipoproteins). Onset typically occurs in childhood or adolescence, and the disease follows a progressive course. There is currently no cure or disease-modifying treatment for HARP syndrome. Management is supportive and symptomatic, focusing on controlling movement disorders with medications such as baclofen or anticholinergics, monitoring and managing visual decline, and providing rehabilitative therapies. Iron chelation therapy has been investigated in PKAN-spectrum disorders but has not demonstrated clear clinical benefit. Genetic counseling is recommended for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about HARP syndrome