Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (
Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive dysmyelinating disorder of the central nervous system, clinically characterized by nystagmus, spasticity, ataxia, and mental retardation
An 11-month-old boy was admitted to Asan Medical Center for evaluation of developmental delays. He was born at term, after a normal pregnancy, with a birth weight of 2,600 g and normal Apgar scores. He had a maternal uncle with developmental delay, but no other family history of related diseases. The patient presented with nystagmus, spasticity, strabismus, and head nodding. When he was 1 month old, his parents noticed jerky eye movements and nodding of his head. Thereafter, he showed frequent head nodding and mild hypertonia in the lower extremities. At the age of 7 months, he underwent a hearing evaluation at another hospital because of suspected deafness. Brainstem auditory evoked potentials were normal, and brain MR imaging showed a choroidal cyst in the right medial temporal lobe. By 11 months of age, he was still unable to sit unaided. At this point, laboratory tests, including those to assess the serum amino acid and urine organic acid levels, were normal. Brain MR imaging was performed and revealed the absence of myelination of the white matter; there had been no progression of myelination compared to brain MR images obtained at 7 months of age (
A 9-month-old girl was referred to Asan Medical Center for evaluation of developmental delays and microcephaly. She was born at term, after a normal pregnancy, with a birth weight of 2,210 g. She did not experience any significant perinatal distress. She was the first child of healthy parents and had no family history of developmental delays. Her height was normal for her age, but her head circumference was below the 3rd percentile for children of her age. A neurologic examination revealed spasticity in all extremities and tremors in the upper extremities. At 1 month of age, fast horizontal nystagmus was noticed. She had difficulty feeding and was unable to hold her head up until she was 8 months old. Even at 9 months of age, she could not maintain a sitting position, and laboratory tests, including serum amino acids and urine organic acid levels, showed normal results. At this point, her developmental state was equivalent to that of a 3- to 4-month-old infant, by the Korean infant and child developmental screening test (KICDT). Electroencephalography (EEG) showed occasional high amplitude delta slowings over both posterior head regions. Analysis of brainstem auditory evoked potentials revealed a central conduction defect on both sides, while visual evoked responses were normal. Brain MR imaging (
A 23-month-old boy with developmental delay was admitted for evaluation of tonic contraction. He was the second child of healthy parents, and his 6-year-old brother was also healthy. He was born at full term and did not experience any abnormal perinatal events. At 4 months of age, he experienced spastic contractures of the lower limbs and was diagnosed with developmental delays at another hospital. By the age of 23 months, he was unable to support his head or turn from a prone to supine position. He had feeding problems, with recurrent vomiting. At 23 months of age, his head circumference was 46 cm (
An 11-months-old boy was admitted for treatment of seizures, which began on the day after his birth. He was born after a full-term, unremarkable pregnancy and delivery, with a birth weight of 3,400 g. On admission, his body weight, height, and head circumference were normal for his age. The patient presented with spastic paraplegia, gastroesophageal reflux, dysphagia, nystagmus, and developmental delays. Auditory evoked potentials were normal, as were laboratory results for serum amino acids and urine organic acids. Genetic analysis of the
A 15-month-old boy was admitted for evaluation of developmental delay. He weighed 3,900 g at birth after an uneventful pregnancy and term delivery. His parents and older sibling were healthy. At 15 months of age, his growth was normal for his age, but he could not hold his head up and was unable to roll over or crawl. Neurologic examination revealed spasticity in all extremities. An EEG revealed multifocal spike discharges. Brainstem auditory evoked potentials were normal. However, brain MR imaging showed delayed myelination (
Among the numerous leukodystrophies with early onset and no biochemical markers, PMD is one that can be identified through a combination of stringent clinical criteria and demonstration of the abnormal formation of myelin. Abnormal myelination can be demonstrated through electrophysiological studies and brain MR imaging
In contrast to other demyelinating leukodystrophies such as metachromatic leukodystrophy and adrenoleukodystrophy, in which myelin is formed but subsequently destroyed, PMD is characterized by the failure of myelin formation. PMD is caused by mutations in the
The clinical features of PMD are variable and include nystagmus, psychomotor delay, seizure, stridor, feeding difficulties, ataxia, and hypotonia progressing to spasticity. Moreover, the degree of dysmyelination is correlated with the severity of the clinical manifestations
Depending on the age of clinical onset, pattern of transmission, and severity of the symptoms at presentation, PMD is classified into 3 subtypes: connatal, classical, and transitional
Brain MR images of PMD patients showed diffuse or patchy T2-hyperintensity due to the lack of myelination
Proton MR spectroscopy reveals changes in cellular metabolism in the central nervous system and may therefore contribute to both the diagnosis of PMD and a better understanding of its pathogenesis
In studies of patients with
On the basis of clinical manifestations, genetic analyses, brain MR imaging, and MR spectroscopic findings, 5 patients (1 girl and 4 boys) were diagnosed with PMD. These case reports suggest that MR spectroscopic images are potentially valuable in evaluating the degree of axonal integrity and myelination in PMD patients. Moreover, we suggest that MR spectroscopy is an important tool for understanding the pathophysiology of PMD. Due to the failure to detect
(A) Axial T2-weighted magnetic resonance imaging (MRI) performed at 11 months of age (case 1) shows the absence of myelination. (B) Axial T2-weighted MRI performed at 9 months of age (case 2) shows decreased white matter volume and the reduction of myelin formation. (C) Axial T2-weighted MRI performed at 23 months of age (case 3) reveals decreased white matter and decreased myelination. (D) Axial T2-weighted MRI obtained at 11 months of age (case 4) shows a hypoplastic corpus callosum and the lack of myelination within the white matter. (E) Axial T2-weighted MRI obtained at 15 months of age (case 5) shows delayed myelination.
(A) Magnetic resonance (MR) spectroscopy in case 1 shows increased N-acetylaspartate (NAA) and creatine peak in the white matter and basal ganglia. (B) MR spectroscopy in case 2 reveals increased NAA and creatine peak in basal ganglia, internal capsule, frontal, and occipital white matter.
(A) Multiplex ligation-dependent probe amplication (MLPA) analysis in case 1 shows duplication of the
Summary of Findings and Clinical Characteristics of Patients with Pelizaeus-Merzbacher Disease
MR, magnetic resonance; NAA, N-acetylaspartate; Cr, creatine; BAEP, brainstem acoustic evoked potential.