Higgins et al. (1992) described a woman with the combination of hyperprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration. She had demonstrated severe spasticity and dystonia since early childhood. At age 10, she was shown on funduscopic examination to ... Higgins et al. (1992) described a woman with the combination of hyperprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration. She had demonstrated severe spasticity and dystonia since early childhood. At age 10, she was shown on funduscopic examination to have pigmentary retinopathy and the 'eye of the tiger' sign on brain MRI. A peripheral blood smear and electron microscopy demonstrated marked acanthocytosis that was not due to an intrinsic erythrocyte protein defect. On high-resolution lipoprotein electrophoresis, she demonstrated absence of the pre-beta fraction, with normal blood levels of cholesterol, triglycerides, high and low density lipoprotein cholesterol, and apolipoproteins A, B, and C. Orrell et al. (1995) described a second case of HARP syndrome in an 18-year-old woman who presented with longstanding intellectual subnormality, night blindness, and a 2-year history of orobuccolingual dystonia causing dysarthria and dysphagia. Investigation showed 53% acanthocytosis and hypoprebetalipoproteinemia, and ERG was typical of tapetoretinal degeneration. MRI showed the 'eye of the tiger' sign. The patient's sister and mother had a similar lipid disorder and acanthocytosis, but no neurologic or retinal disease. The authors noted that HARP syndrome shares many clinical and radiographic features with PKAN, including the 'eye of the tiger' sign, but is distinguished by a specific lipoprotein abnormality.
Ching et al. (2002) studied the original patient reported by Higgins et al. (1992) and identified an arg371-to-ter (R371X) mutation in the PANK2 gene (606157.0011). This finding established that HARP is part of the PKAN disease spectrum. ... Ching et al. (2002) studied the original patient reported by Higgins et al. (1992) and identified an arg371-to-ter (R371X) mutation in the PANK2 gene (606157.0011). This finding established that HARP is part of the PKAN disease spectrum. In a patient with HARP syndrome initially reported by Orrell et al. (1995), Houlden et al. (2003) identified compound heterozygosity for mutations in the PANK2 gene: a met327-to-thr substitution (M327T; 606157.0012) and a splice site mutation (606157.0013). The patient's mother and sister, both of whom had acanthocytosis and hypoprebetalipoproteinemia without neurologic abnormalities, were heterozygous for the splice site mutation, whereas her unaffected father was heterozygous for the M327T mutation.