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Table of Contents    
Year : 2013  |  Volume : 61  |  Issue : 5  |  Page : 537-539

Mucolipidosis and progressive myoclonus epilepsy: A distinctive phenotype

1 Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India
2 Department of Neuropathology, National Institute for Mental Health and Neurological Sciences, Bengaluru, Karnataka, India

Date of Submission13-Aug-2013
Date of Decision16-Aug-2013
Date of Acceptance20-Oct-2013
Date of Web Publication22-Nov-2013

Correspondence Address:
Ramshekhar N Menon
Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.121943

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How to cite this article:
Menon RN, Jagtap S, Thakkar R, Narayanappa G, Nair M. Mucolipidosis and progressive myoclonus epilepsy: A distinctive phenotype. Neurol India 2013;61:537-9

How to cite this URL:
Menon RN, Jagtap S, Thakkar R, Narayanappa G, Nair M. Mucolipidosis and progressive myoclonus epilepsy: A distinctive phenotype. Neurol India [serial online] 2013 [cited 2023 Dec 6];61:537-9. Available from:


A 9-year-old boy, the second product of a non- consanguineous parentage presented with moderate to severe developmental delay and with recurrent tonic seizures since 7 years of age. His developmental age prior to presentation was at 3-year level for gross and fine motor skills and for language was 18 months. There was global regression 6 months after the onset of seizures. Seizures remained medically refractory. Subsequent deterioration occurred in the form of global regression with progressive ataxia, loss of visual fixation and mutism. This was followed by random chaotic jerks of the limbs and trunk.

Neurological examination revealed a bed ridden child with poor auditory, visual regard and truncal hypotonia. Bilateral optic disc pallor was evident with no cherry red spot or retinitis pigmentosa. Bipyramidal signs, ataxia, elbow contractures and multifocal myoclonus were noted. There was no organomegaly. Hematology and routine biochemistry was normal. Video-electroencephalogram (EEG) [Figure 1] was consistent with a symptomatic generalized epilepsy with no photosensitivity. Random multifocal myoclonic jerks had diffuse EEG correlates [Figure 1]. Attenuation of visual evoked potentials was noted. Brain magnetic resonance imaging revealed mild diffuse atrophy with a thin corpus callosum [Figure 2]. Electron microscopy (EM) of skin biopsy specimen revealed membrane bound concentric lamellar inclusions and Zebra bodies within the glandular epithelium [Figure 3], considered diagnostic of mucolipidosis type IV (ML-IV). Enzyme and genetic analysis could not be done. The child was managed with valproate and clonazepam with no significant improvement in his clinical status.
Figure 1: Electroencephalogram (a) axial myoclonic jerks with characteristic burst of posterior predominant generalized sharp and slow wave followed by a period of attenuation of background activity, (b and c) interictal activity-profuse background slowing with multifocal and generalized epileptiform discharges, (d) recorded asymmetric tonic seizures of diffuse electrodecremental ictal onset

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Figure 2: Magnetic resonance imaging brain (axial, saggital and coronal images)-mild-moderate diffuse atrophy with characteristic thinning of corpus callosum

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Figure 3: Skin biopsy: Electromicrograph showing low (a) and high (b) magnification of glandular epithelium with membrane bound concentric lamellar inclusion, zebra bodies. (c) Lamellar inclusions at high magnification

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ML-IV is a neurodegenerative disorder with severe developmental delay, progressive visual impairment and often incidentally diagnosed achlorydria. The characteristic phenotype of children with ML-IV is marked by psychomotor delay, corneal clouding, optic atrophy, retinal dystrophy and squint. [1],[2] Described dysmorphic features such as puffy eyelids and coarse facies were absent in our patient. Presentation at birth with the global developmental delay, often suggests intrauterine growth retardation. The development age for language and motor functions never progress beyond the 12-15 months. However, in some patients, slow but continuous improvements in cognitive, language and motor functions have been reported. [3]

A constellation of psychomotor regression, multiple independent spike foci with generalized epileptiform discharges on EEG and cortical-subcortical myoclonias prompts an evaluation for disorders like progressive myoclonus epilepsy (PME). This presentation of ML-IV is highly atypical taking into consideration the largest reported skin biopsy-proven series from India. [4] This cohort of 4 patients had a uniform presentation in adolescence with slowly progressive spastic paraparesis in stark contrast to the early age and epilepsy evident in our patient. In addition, optic atrophy, absence of the characteristic corneal clouding and thin corpus callosum were consistent features. Our case demonstrates the variability in the phenotypic manifestations of this disorder with no reports in literature on ML-IV presenting as PME syndrome.

ML-IV is an autosomal recessive disease caused by mutations in MCOLN1, which encodes for mucolipin-1, a member of the transient receptor potential cation channel family. [5] Alterations in mucolipin leads to accumulation of heterogenous lipids and proteins in the cytosol vacuoles derived from lysosomes. EM examination of skin biopsies is a useful and relatively inexpensive method to screen for lysosomal storage diseases and for diagnosis of conditions for which there are no specific molecular or genetic tests. EM studies of biopsy specimens taken from skin, conjunctiva, peripheral nerve, muscle, and liver show two types of inclusions in ML-IV, membrane-bound vesicles filled with granular material and concentric lamellar bodies. [5] The skin biopsy findings in our patient were consistent with those previously reported. The various forms of late infantile, juvenile, and adult onset neuronal ceroid lipofuscinoses are characterized by inclusion of either curvilinear and/or finger print bodies as opposed to membrane cytoplasmic or zebra bodies as seen in ML-IV. [5] Phospholipids, mucopolysaccharides and gangliosides are found in these inclusion bodies. [6] Interestingly, these abnormalities are similar to those seen in cells of patients with GM2-gangliosidosis Type I or Tay-Sachs disease, fucosidosis, galactosialidosis or sialidosis. [5] The morphology, however, of the storage material in skin biopsies of ML-IV patients is unique, enabling biopsies to be used for diagnostic purposes.

 » References Top

1.Altarescu G, Sun M, Moore DF, Smith JA, Wiggs EA, Solomon BI, et al. The neurogenetics of mucolipidosis type IV. Neurology 2002;59:306-13.  Back to cited text no. 1
2.Bonavita S, Virta A, Jeffries N, Goldin E, Tedeschi G, Schiffmann R. Diffuse neuroaxonal involvement in mucolipidosis IV as assessed by proton magnetic resonance spectroscopic imaging. J Child Neurol 2003;18:443-9.  Back to cited text no. 2
3.Chitayat D, Meunier CM, Hodgkinson KA, Silver K, Flanders M, Anderson IJ, et al. Mucolipidosis type IV: Clinical manifestations and natural history. Am J Med Genet 1991;41:313-8.  Back to cited text no. 3
4.Bindu PS, Gayathri N, Yasha TC, Kovoor JM, Subasree R, Rao S, et al. A variant form of mucolipidosis IV: Report on 4 patients from the Indian subcontinent. J Child Neurol 2008;23:1443-6.  Back to cited text no. 4
5.Alroy J, Ucci AA. Skin biopsy: A useful tool in the diagnosis of lysosomal storage diseases. Ultrastruct Pathol 2006;30:489-503.  Back to cited text no. 5
6.Wakabayashi K, Gustafson AM, Sidransky E, Goldin E. Mucolipidosis type IV: An update. Mol Genet Metab 2011;104:206-13.  Back to cited text no. 6


  [Figure 1], [Figure 2], [Figure 3]

This article has been cited by
1 Progressive Myoklonusepilepsien
Günter Krämer
Zeitschrift für Epileptologie. 2022;
[Pubmed] | [DOI]
2 Progressive myoclonic epilepsies—English Version
Günter Krämer
Zeitschrift für Epileptologie. 2022;
[Pubmed] | [DOI]


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