Printer Friendly

A rare case of Palizaeus Merzbacher Disease in a female patient diagnosed radiologically.

Byline: Naseebullah Maimoona Siddiqui Sadia Saeed and Yousuf Chaudary


Pelizaeus Merzbacher's Disease is an inherited X-linked recessive trait. Males have the disease while females are usually carriers. We report the case of a 6-years-old girl who had nystagmus since birth and later on developed head nodding. She started talking at one year and walking at 18 months. Then she developed regression of milestones with speech impairment and inability to walk which progressively worsened. Before presenting she had a generalised seizure. Her parents were second cousins. Family history was unremarkable. On examination she was awake alert there was bilateral horizontal nystagmus. Cranial nerve examination was normal. There was spastic paraparesis with bilateral extensor plantar response. Magnetic resonance imaging of the brain showed classical features of diffuse hypomyelination characteristic of Pelizaeus Merzbacher's Disease for this age group.

Keywords: Pelizaeus Merzbacher's disease Age group.


Pelizaeus Merzbacher's Disease (PMD) also called leukodystrophy hypomyelinating 1 (HDL1) is an inherited allelic leukodystrophy caused by mutations of the proteolipid protein 1 gene (PLP1). PMD is inherited as an X-linked recessive trait. Males with PLP1 mutations have the disease while females are usually unaffected carriers.1

Case Report

We report the case of a six-years-old girl born in hospital at full term through spontaneous vaginal delivery. She cried well soon after birth and no cyanosis or jaundice was observed at that time. The patient had nystagmus since birth and later on developed head nodding. She had normal attainment of milestones initially with suckling neck holding social smile at proper ages etc. She started uttering one or two words at one year of age and started to walk at 18 months. Thereon the milestones started regressing with speech impairment and inability to walk that progressively worsened leaving her bedridden for the preceding two years. Before presenting to our clinic she had a generalised seizure. Her parents were second cousins and it was a consanguineous marriage. She had 5 siblings. All were alive and healthy. Family history was unremarkable for any major illnesses. On examination she was awake and was following commands.

Pupils were bilaterally equal and reactive. Spontaneous nystagmus was present bilaterally in horizontal direction. Cranial nerve examination was normal. There was spastic paraparesis with bilateral up- going plantars. Magnetic resonance imaging (MRI) of the brain had classical features of diffuse hypomyelination which is characteristic of PMD for this age group. Electroencephalography (EEG) showed mild encephalopathy.


PMD is an X-linked leukodystrophy leading to hypomyelination of the brain and spinal cord. It is seen rarely in clinical practice and still rarer in females. Its clinical features were initially highlighted by Pelizaeus in 1885 and later on in 1910 Merzbacher described a family with this genetic disease with details of pathological features.1

Our patient was female and was yet hit by PMD even though mutations of deletion can rarely cause disease in females. The reason for it could be that patients with PMD1 have homozygous or compound heterozygous mutations and can affect both males and females equally.2

It is a slowly progressive disease leading to death in the first decade or early adult life. There are point mutations in PLP1 gene at the region of X q21-223 leading to micro- deletion or duplication of the aminoacids involved in the formation of oligodendrocytes required for myelination of the brain and spinal cord.

There are at least two other case reports of PMD in female patients from Japan in 19964 and Israel in 2009.5

It can be misdiagnosed as cerebral palsy in clinical practice bur MRI brain shows the classical hypomyelination typical of the disease (Figure-1 and 2). Furthermore Brainstem Auditory Evoked Potentials (BAEP) and Somatosensory Evoked Potentials (SSEP) remain abnormal throughout the course of the disease. Visual Evoked Potentials are inconsistent.

Respiratory distress and stridor is common and important cause of morbidity/mortality in more severe forms of PMD.6

The white matter is isointense on T1-weighted image non-enhancing on gadolinium contrast. T2-weighted and fluid attenuation inversion recovery (FLAIR) images show diffuse hyper-intense signals in the whole distribution of white matter called diffuse hypomelination characteristic of PMD.


PMD is an X-linked recessive leukodystrophy that should be suspected in children with regression of milestones.


1. Boulloche J Aicardi J. Pelizaeus-Merzbacher disease: clinical and nosological study. J Child Neurol 1986; 1: 233-9.

2. Uhlenberg B Schuelke M RA1/4schendorf F Ruf N Kaindl AM Henneke M et al. Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) causes Pelizaeus-Merzbacher- like disease. Am J Hum Genet 2004; 75: 251-60.

3. Mattei MG Alliel PM Dautigny A Passage E Pham-Dinh D Mattei JF et al. The gene encoding for the major brain PLP maps to the q-22 band of the human X chromosome. Hum Genet 1986; 72: 352-3.

4. Nezu A Kimura Sa Ueharaa S Osaka Ha Kobayashi Ta Haraguchi Ma et al. Pelizaeus-Merzbacher-like disease: female case report. Brain Dev 1996; 18: 114-8.

5. Fattal-Valevski A DiMaio MS Hisama FM Hobson GM Davis- Williams A Garbern JYetal. Variable Expression of a Novel PLP1 Mutation in Members of a Family With Pelizaeus-Merzbacher Disease. J Child Neurol 2009 24: 618-24.

6. Hudson LD. Pelizaeus-Merzbacher disease and spastic paraplegia type 2: two faces of myelin loss from mutations in the same gene. J Child Neurol 2003; 18: 616-24.
COPYRIGHT 2014 Asianet-Pakistan
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2014 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Publication:Journal of Pakistan Medical Association
Date:Nov 30, 2014
Previous Article:Is it safe to be calcified Porcelain gallbladder perforation and review of literature.
Next Article:Eagle syndrome; radiological evaluation and management.

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters