Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurodegenerative disease characterized by abnormal accumulation of iron in distinct brain areas. It has an estimated worldwide incidence of 2 affected individuals in 1 million which is even lower among the African population (Brezavar and Bonnen 2019). However, in the heterogenous group of neurodegenerative disorders with brain iron accumulation (NBIA), it is considered to be the most common (Hayflick et al. 2003;Hartig et al. 2006). PKAN is a genetically inheritable disease following an autosomal recessive pattern with causative mutations in the pantothenate kinase 2 (PANK2) gene. Pantothenate kinases control the biosynthesis of the coenzyme A (Zhou et al. 2001).
Clinically, PKAN shows a wide range of signs and symptoms including motor manifestations, e.g., dystonia, parkinsonism, dysarthria, dysphagia and spasticity, psychiatric and cognitive impairment as well as oculomotor disturbances (Lee et al. 2016). According to age of onset and disease progression, PKAN is classified into typical and atypical types. Atypical PKAN is characterized by later onset and slower progression (Hartig et al. 2006). Genetic determinants of PKAN, however, are not well characterized. Additionally, the current knowledge about PKAN is mainly built on individual case reports and case series (Marshall et al. 2019). The disease progression, severity of symptoms and even correlation between specific mutations and the disease phenotype is highly variable (Tomic et al., 2015).
Neurogenetic studies about PKAN are scarce in North Africa. So far, only one case report described a female patient with PKAN in a consanguineous Moroccan family, identifying a causative homozygous deletion in PANK2 (Efthymiou et al., 2020). In the present study, we describe an Egyptian family with 4 affected members revealing slow progression of atypical PKAN. The patients had different ages of onset and showed variable clinical presentations (parkinsonism, dystonia), normal serum ferritin levels, absence of acanthocytes, the brain MRI characteristic eye-of-the-tiger sign, all caused by the same homozygous mutation in PANK2.