Homozygous Mutation of the AP4E1 Gene as a Cause of Autosomal Recessive Spastic Paraplegia Type 51 (SPG51) in a 17-Years-Old Boy | Chapter 6 | An Overview of Disease and Health Research Vol. 3

Autosomal recessive spastic paraplegia-51 (SPG51) is a rare neurodevelopmental disorder caused by a homozygous mutation in the AP4E1 gene, located on chromosome 15q21. SPG51 is characterized by neonatal hypotonia that progresses to hypertonia and spasticity. This is an often underdiagnosed condition in childhood, frequently presenting with clinical inconsistencies that can lead to misdiagnosis. Due to clinical overlap with conditions like cerebral palsy and other hereditary spastic paraplegias (e.g., SPG47, SPG50, SPG52), SPG51 is frequently underdiagnosed. Mutations in the AP-4E1 gene on chromosome 15q21.2 can lead to SPG51. Different mutations in this gene have been identified in affected individuals, leading to disruption of the AP4 complex and vesicular trafficking processes. The specific characteristics of SPG51 are, due to only a few cases, not well understood, due to limited reports of affected families. Affected individuals also have global developmental delay with impaired intellectual development and poor or absent speech. They typically present with hypotonia in the neonatal period, which progresses to muscular hypertonia, especially in the lower limbs. They may also exhibit contractures, talipes equinovarus, decreased muscle mass, short stature, and microcephaly. Severe mental retardation, absent speech, and dysmorphic facial features are common. Some patients may experience seizures. Neurological examination often reveals spastic paraplegia of the lower limbs, and brain imaging may show atrophy of the cerebellar vermis and cortical atrophy.

 

This study presents an extremely rare case of a 17 years-old boy with autosomal recessive spastic paraplegia type 51. A compound heterozygous mutation in the AP4E1 gene was found in genetic analysis. The most disruptive symptoms were severe episodes of restlessness and aggression, particularly triggered by unfamiliar people and environments, including within the home. This case highlights the phenotypic variability of SPG51 and the importance of genetic testing and careful clinical evaluation in suspected cases of hereditary spastic paraplegia for accurate diagnosis.

 

Author(s) Details

 

Stefan Bittmann
Department of Pediatrics, Ped Mind Institute (PMI), Hindenburgring 4, D-48599 Gronau, Germany and Shangluo Vocational and Technical College, Shangluo, Shaanxi, China.

 

Please see the book here:- https://doi.org/10.9734/bpi/aodhr/v3/5687