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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 5  |  Page : 1456-1458

Hurler Phenotype with Vacuolated Lymphocytes and Elevated Lysosomal Hydrolases – Is it Mucolipidosis?

1 Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission02-Jun-2018
Date of Decision08-Jul-2020
Date of Acceptance18-Jul-2020
Date of Web Publication30-Oct-2021

Correspondence Address:
Naveen Sankhyan
Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.329583

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How to cite this article:
Sharawat IK, Kasinathan A, Das G, Bhatia P, Sankhyan N. Hurler Phenotype with Vacuolated Lymphocytes and Elevated Lysosomal Hydrolases – Is it Mucolipidosis?. Neurol India 2021;69:1456-8

How to cite this URL:
Sharawat IK, Kasinathan A, Das G, Bhatia P, Sankhyan N. Hurler Phenotype with Vacuolated Lymphocytes and Elevated Lysosomal Hydrolases – Is it Mucolipidosis?. Neurol India [serial online] 2021 [cited 2021 Nov 30];69:1456-8. Available from:


A 3-year-old girl presented with concerns of delayed attainment of developmental milestones since late infancy and progressive abdominal distension since 1 year of age. She was first born to non-consanguineous parents. She was gaining milestones normally till 7 to 9 months of age. After 9 months of age, parents noticed that there was a delay in the attainment of further milestones with progressive abdominal distension. Marked coarsening of facial features were also observed [Figure 1]. Family history was noninformative. On examination, she had chronic malnutrition, anemia, and microcephaly (-5 z score). She had coarse facies with prominent metopic suture, bi-temporal hollowing, supraorbital hollowing, flattened nasal bridge, upturned and short nose, clear cornea, low set ears, full lips and cheeks, gingival hyperplasia, macrostomia, macroglossia, and long philtrum. She also had short, incurved, stubby fingers with thickened skin texture. Contractures were noted at finger joints, knee, ankle, wrist, and elbow. Marked hepatosplenomegaly with the umbilical hernia was striking. Owing to the Hurler phenotype with marked gingival hyperplasia, differentials considered were mucolipidosis; GM1 gangliosidosis and sialidosis.
Figure 1: Serial photographs illustrating the progressive coarsening of facial features ((a): at 8 months, (b): 12 months, (c): 15 months, (d): 3 years of age) with a large tongue, gingival hypertrophy

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The urine sample for glyocosaminoglycans was negative. Skeletal X-rays showed paddle-shaped ribs, periosteal cloaking; metaphyseal widening of long bones, J-shaped sella, shallow acetabulum, bullet-shaped metacarpals, and anterior beaking of vertebral bodies [Figure 2]. Peripheral smear showed vacuolated lymphocytes [Figure 3]. Vitamin D and parathyroid hormone levels were normal. Enzyme assay for arylsulphatase A and β-D-hexosaminidase showed nearly seven-fold elevation (462 nmol/h/mg and 104 nmol/min/mg, respectively). The cardiac screening was unremarkable. Genetic testing was not performed due to financial constraints.
Figure 2: Skeletal survey illustrating Periosteal cloaking, Metaphyseal widening of long bones lower (a), J shaped sella (b), Pelvic dysplasia with shallow acetabulum (c), Bullet-shaped metacarpals and delayed bone age (d), and anterior beaking of vertebral bodies (e)

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Figure 3: Microscopic photograph of the peripheral blood smear showing the presence of multiple vacuoles in lymphocytes (arrow) under high power 100×; Oil immersion

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Mucolipidosis type 2 (ML2) or I cell disease is a slowly progressive autosomal recessive lysosomal storage disorder caused by a mutation in the GNPTAB gene with resultant uridine diphosphate-N-acetylglucosamine-1 phosphotransferase enzyme deficiency.[1],[2] The deficiency of this enzyme leads to abnormal enzyme trafficking characterized by marked elevation of lysosomal hydrolases enzymes.[3] The clinical presentation is diverse ranging from neonatal onset generalized hypotonia, chubby face with thick wax-like skin around the ear lobule to infantile onset Hurler phenotype, early-onset joint contractures, cardiomyopathy, and skeletal deformities. While ML2 patients typically present with the classic Hurler phenotype, certain clinical features are strikingly distinguishing. Distinct gingival hypertrophy, prominent metopic suture, relatively preserved cognition, early-onset joint contractures, and thick wax-like skin are conspicuous.[4],[5] Given the exuberant pricing of genetic testing, a reasonable clue to the diagnosis is the 5 to 20 fold elevation of all lysosomal hydrolases in the plasma and other body fluids. The commonly elevated enzymes are arylsulfatase A, β-D-galactosidase, β-D-hexosaminidase, β-D-glucoronidase, and α-L-fucosidase levels.[6] The index patient also had a seven-fold elevation of arylsulfatase A and β-D-hexosaminidase levels. Another pointer to the diagnosis is the elevated levels of oligosaccharides in the urine in the absence of glycosaminoglycans.[6] The diagnosis of the condition is made by the constellation of clinical features, elevated urinary levels of oligosaccharides, near-complete absence of uridine diphosphate-N-acetylglucosamine-1 phosphotransferase enzyme activity. Detection of deletions and duplications in the GNPTAB gene is confirmatory.[7]

A heightened index of suspicion for mucolipidosis should be considered in children with Hurler phenotype and marked gingival hyperplasia. Judicious use of simple tests such as urine oligosaccharides and enzyme hydrolase assay are cost-effective and may clinch the diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Tiede S, Storch S, Lübke T, Henrissat B, Bargal R, Raas-Rothschild A, et al. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1 phosphotransferase. Nat Med 2005;11:1109-12.  Back to cited text no. 1
Encarnação M, Lacerda L, Costa R, Prata MJ, Coutinho MF, Ribeiro H, et al. Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III – identification of eight novel mutations. Clin Genet 2009;76:76-84.  Back to cited text no. 2
Bargal R, Zeigler M, Abu-Libdeh B, Zuri V, Mandel H, Ben Neriah Z, et al. When mucolipidosis III meets mucolipidosis II: GNPTA gene mutations in 24 patients. Mol Genet Metab 2006;88:359-63.  Back to cited text no. 3
Cathey SS, Leroy JG, Wood T, Eaves K, Simensen RJ, Kudo K, et al. Phenotype and genotype in mucolipidoses II and III alpha/beta: A study of 61 probands. J Med Genet 2010;47:38-48.  Back to cited text no. 4
Spranger JW, Brill PW, Poznanski A. Bone Dysplasias: Atlas of Genetic Disorders of Skeletal Development. 2nd ed. New York, NY: Oxford University Press; 2002. p. 295-9.  Back to cited text no. 5
Paik KH, Song SM, Ki CS, Yu HW, Kim JS, Min KH, et al. Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc-phosphotransferase alpha/beta subunits in Korean patients with mucolipidosis type II ortype IIIA. Hum Mutat 2005;26:308-14.  Back to cited text no. 6
Otomo T, Muramatsu T, Yorifuji T, Okuyama T, Nakabayashi H, Fukao T, et al. Mucolipidosis II and III alpha/beta: Mutation analysis of 40 Japanese patients showed genotype-phenotype correlation. J Hum Genet 2009;54:145-51.  Back to cited text no. 7


  [Figure 1], [Figure 2], [Figure 3]


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