Elevation of neuron specific enolase and brain iron deposition on susceptibility‐weighted imaging as diagnostic clues for beta‐propeller protein‐associated neurodegeneration in early childhood: Additional case report and review of the literature

Abstract

Beta-propeller protein-associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a subtype of neurodegeneration with brain iron accumulation (NBIA). BPAN is caused by mutations in an X-linked gene WDR45 that is involved in autophagy. BPAN is characterized by developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. Brain magnetic resonance imaging (MRI) shows iron deposition in the bilateral globus pallidus (GP) and substantia nigra (SN). Clinical manifestations and laboratory findings in early childhood are limited. We report a 3-year-old girl with BPAN who presented with severe developmental delay and characteristic facial features. In addition to chronic elevation of serum aspartate transaminase, lactate dehydrogenase, creatine kinase, and soluble interleukin-2 receptor, she had persistent elevation of neuron specific enolase (NSE) in serum and cerebrospinal fluid. MRI using susceptibility-weighted imaging (SWI) demonstrated iron accumulation in the GP and SN bilaterally. Targeted next-generation sequencing identified a de novo splice-site mutation, c.831-1G>C in WDR45, which resulted in aberrant splicing evidenced by reverse transcriptase-PCR. Persistent elevation of NSE and iron deposition on SWI may provide clues for diagnosis of BPAN in early childhood.

Beta‐propeller protein‐associated neurodegeneration: a case report and review of the literature

“…A total of 64 patients were included in the analysis, comprising 55 women (85.9%) and nine men (14.1%) (Tables and ) . Mean age at diagnosis was 27.6 ± 14 years (range 1–52), and mean age at deterioration was 27.2 ± 5.7 (range 13–39).…”

“…Other features included cerebral atrophy (44/64, 68.8%), cerebellar atrophy (17/64, 26.6%), delayed myelination [6,9,15,26], thin corpus callosum [25,26], and dilated ventricles [9,10]. Radiological features are summarized in Table 3.…”

“…A wide range of sleep disturbances has been reported including REM sleep disorder , excessive movement during sleep , circadian rhythm sleep disorder , hypersomnolence with choreiform movements at onset of sleep , parasomnia with nocturnal screaming , and unspecified sleep disorders . Ocular/visual involvement has been reported in 17 patients and comprises myopia , astigmatism , strabismus , abnormal pupillary shade , spontaneous retinal detachment , bilateral partial retinal coloboma , patchy loss of pupillary ruff , difficulties with eyesight with intermittent double‐vision , bilateral optic disk pallor , bilateral optic atrophy , increased visual evoked potential (VEP) latency , cortical blindness , and retinitis pigmentosa .…”

“…Definite data were only available for 16 of 64 patients (25%) of whom 11 (68.8%) were reported to have dysmorphic features. These included microcephaly , abnormal nasal bridge (depressed, high, wide, and flat) , a small mouth , tented upper lip , hypertelorism , epicanthal folds , downslanting palpebral fissures , large ears , bilateral low‐set ears , low hanging columella , short philtrum , high palate , downturned mouth and micrognathia , narrow face , narrow nose , thin upper lip , kyphosis , flat and almost rocker bottom feet , fingers tapered with fifth finger clinodactyly , partial synophrys , and congenital talipes varus . Small cold hands and feet were also reported .…”

Substantia Nigra Swelling and Dentate Nucleus T2 Hyperintensity May Be Early Magnetic Resonance Imaging Signs of β‐Propeller Protein‐Associated Neurodegeneration

“…Persistently high levels of neuron-specific enolase in cerebrospinal fluid and serum, and of markers of abnormal myocyte activity (transaminases, creatine kinase, and lactate dehydrogenase) have been described in association with BPAN, and proposed as early signs of the disease. 28,29 These examinations were not performed in our patients.…”