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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 6  |  Page : 1753-1755

Mucopolysacharidosis Type I Presenting as Bipolar Affective Disorder: A Case Report

Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum-11, India

Date of Submission07-Jan-2020
Date of Decision11-Jul-2020
Date of Acceptance14-Jul-2021
Date of Web Publication23-Dec-2021

Correspondence Address:
Dr. Sapna Erat Sreedharan
Additional Professor, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum-11
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.333455

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 » Abstract 

Mucopolysacharidosis type I is a multisystem disease and often presents with neurobehavioral problems, corneal clouding, cardiac valve involvement, hepatomegaly, coarse facies, and skeletal abnormalities. It has three subtypes – with Hurler subtype (MPS-1H) being the most severe phenotype with early neurological involvement, rapid progression and mortality, while the other two subtypes – Hurler-Scheie (MPS-1H/S) and Scheie (MPS-1S) are of intermediate and milder severity, respectively. Even though neuropsychiatric symptoms have often been reported in the pediatric age group, MPS type I presenting as a major psychiatric illness in adulthood has rarely been reported in literature. Here, we report a female presenting as bipolar affective disorder in the fourth decade of life, where neuroimaging and systemic involvement gave a clue to the diagnosis.

Keywords: Aortic stenosis, MRI, mucopolysacharidosis, psychiatric
Key Message: Mucopolysacharidosis is a rare lysosomal storage disease that can have neurological and non-neurological presentations. Here, we present a patient with adult onset bipolar affective disorder, where brain imaging, cardiac, and skeletal involvement gave clue to the etiology.

How to cite this article:
Saraf UU, Jose J, Krishnan S, Sreedharan SE. Mucopolysacharidosis Type I Presenting as Bipolar Affective Disorder: A Case Report. Neurol India 2021;69:1753-5

How to cite this URL:
Saraf UU, Jose J, Krishnan S, Sreedharan SE. Mucopolysacharidosis Type I Presenting as Bipolar Affective Disorder: A Case Report. Neurol India [serial online] 2021 [cited 2022 Jan 18];69:1753-5. Available from:

A 36-year-old lady, postgraduate in English, presented to us with a history of psychiatric symptoms initially characterized by excessive talkativeness and jocularity, reduced sleep, grandiose delusions, and auditory hallucinations four years back. She was admitted in a psychiatric facility, diagnosed as mania and was started on mood stabilizers and antipsychotics. She stabilized and started going for job. After 2 years, she discontinued medications. Six months later, relatives noticed that she became withdrawn, with reduced talk and stopped going for work. Two months before presentation, she started refusing feeds and used to spit out food and saliva. She always preferred lying in bed and would refuse to walk or attend to toilet needs herself. She also gave a history of three episodes of syncope in the last three years. She was taken to a nearby hospital, evaluated with MRI Brain, empirically started on antituberculous therapy and referred to us for further management.

Patient was short statured (140 cm) and had an ejection systolic murmur in the aortic area, suggestive of aortic stenosis. She had depressed mood with mild cognitive dysfunction-in the domain of attention. Rest of the neurological examination, including head circumference, was normal.

Blood investigations including hemogram and biochemistry were normal. CSF study showed no cells, normal sugars, and mildly elevated protein (99 mg/dl), with workup for chronic infections coming as negative. MRI Brain showed symmetrical T2 hyper intensities in bilateral putamen and thalami with cribriform appearance with hydrocephalus [Figure 1]a,[Figure 1]b,[Figure 1]c. MRI spine showed cervical spinal canal stenosis with dural thickening [Figure 1]d. Two-dimensional echo confirmed diagnosis of aortic stenosis. In view of multisystem presentation with aortic stenosis, cervical spinal canal stenosis, and neuroimaging findings, possibility of milder phenotype of mucopolysaccharidosis (MPS) presenting in adulthood was considered and blood was send for clinical exome sequencing (Medgenome Lab, Bangalore). Genetic testing revealed a homozygous missense variation of IDUA gene in Exon 6, which has been previously reported in MPS 1H.
Figure 1: MRI T2 Axial sections showing symmetric T2HI involving bilateral thalami (a) and putamen (b), which was also observed in sagittal image (c). Cervical spine MRI sagittal T2 sequences showed high cervical spinal canal stenosis (d)

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The patient was restarted on mood stabilizers, and on 6-month follow-up was euthymic with no new neurological complaints. Enzyme replacement therapy (ERT) has not been initiated in her due to financial reasons.

 » Discussion Top

MPS is a group of lysosomal storage disorders resulting from failure to degrade glycosaminoglycans (GAG) or mucopolysaccharides. This results in accumulation of GAG causing widespread tissue and organ damage. Patient's phenotype can range from mild to severe forms.[1] In the largest global database on MPS-1, only 12 patients have been included from Asia-Pacific region of milder phenotype that itself shows rarity of the disease.[1] Patients with mild expression of the disease have no significant mental deterioration. Cognitive and behavioral problems can be the presenting symptom in MPS I, II, III, and VII in pediatric population and can include aggressiveness, hyperactive behavior, sleep problems, and cognitive delay or deterioration.[2],[3] Severe psychiatric symptoms as presentation have been reported rarely in MPS I patients with specific mutation[4] but along with multidomain cognitive deficits-especially of attention and memory.

Enlarged perivascular spaces (PVS), parenchymal signal alterations and ventriculomegaly have been found to be the most common MRI findings in patients with neurological involvement in MPS 1 and may not always correlate with clinical severity.[5] Dilated PVS may represent the disorder of CSF hydrodynamics representing abnormal CSF circulation. Cardiac involvement in the form of left-sided valvular dysfunction and ventricular hypertrophy are common and early features in MPS 1, which was also found in our patient. Skeletal involvement commonly described in MPS 1 is kyphoscoliosis, with cervical spinal canal stenosis reported more often with type VI.

At present management of neuropsychiatric syndrome is mainly symptomatic treatment with antipsychotics and mood stabilizers along with behavioral management yielding best results.[3] Definitive treatment for preventing organ damage include hematopoietic stem cell transplant if the diagnosis is made before two and a half years and ERT thereafter.[6]

Our patient represents a case of milder phenotype of MPS I presenting with major psychiatric illness, which is a rare presentation of this genetic condition in adulthood. Neuropsychiatric presentation can be there is less than 10% of MPS-1 of milder phenotypes-HS and Scheie subtypes, which is mainly frontal dysexecutive syndrome.[1] Presentation as a major psychiatric illness, rarely reported in literature, is often in the setting of rare L238Q mutation in pediatric age group.[4] We could come across a few case reports from India on MPS-1, presenting with coarse facies, skeletal features, dental abnormalities, mental subnormality, and corneal clouding mostly in pediatric age group.[7],[8],[9],[10] This type of rare presentation of MPS-1 in adulthood has so far not been reported from India, to the best of our knowledge. In our patient, extra-neurological involvement and brain imaging gave an etiological clue, which could be confirmed by genetic testing.

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There are no conflicts of interest.

 » References Top

Beck M, Arn P, Giugliani R, Muenzer J, Okuyama T, Taylor J, et al. The natural history of MPS I: Global perspectives from the MPS I registry. Genet Med 2014;16:759-65.  Back to cited text no. 1
Shapiro EG, Jones SA, Escolar ML. Developmental and behavioral aspects of mucopolysaccharidoses with brain manifestations — Neurological signs and symptoms. Mol Genet Meta 2017;122:1-7.  Back to cited text no. 2
Escolar ML, Jones SA, Shapiro EG, Horovitz DDG, Lampe C, Amartino H. Practical management of behavioral problems in mucopolysaccharidoses disorders. Mol Genet Metab 2017;122S: 35-40.  Back to cited text no. 3
Ahmed A, Whitley CB, Cooksley R, Rudser K, Cagle S, Ali N, et al. Neurocognitive and neuropsychiatric phenotypes associated with the mutation L238Q of the alpha-L-iduronidase gene in Hurler-Scheie syndrome. Mol Genet Metab 2014;111:123-7.  Back to cited text no. 4
Matheus MG, Castillo M, Smith JK, Armao D, Towle D, Muenzer J. Brain MRI findings in patients with mucopolysaccharidosis types I and II and mild clinical presentation. Neuroradiology 2004;46:666-72.  Back to cited text no. 5
de Ru MH, Boelens JJ, Das AM, Jones SA, van der Lee JH, Mahlaoui N, et al. Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: Results of a European consensus procedure. Orphanet J Rare Dis 2011;6:55-64.  Back to cited text no. 6
Sharvil S. Gadve, Dipti Sarma, Uma K. Saikia Short stature with umbilical hernia – Not always due to cretinism: A report of two cases. Indian J Endocrinol Metab 2012;16:453-6.  Back to cited text no. 7
Sharma S, Sabharwal JR, Datta P, Sood S. Clinical manifestation of Hurler syndrome in a 7 year old child. Contemp Clin Dent 2012;3:86-9.  Back to cited text no. 8
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Chakraborty PP, Biswas SN, Ray S, Dey SK. Mucopolysaccharidosis type I disguised as rickets. BMJ Case Rep 2016;2016:bcr2016215416.  Back to cited text no. 9
Sati A, Ramappa M, Chaurasia S, Prasad SM. Deep anterior lamellar keratoplasty in case of Hurler-Scheie syndrome. BMJ Case Rep 2014;2014:bcr2013202730.  Back to cited text no. 10


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