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

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

Indar K Sharawat1, Ananthanarayanan Kasinathan1, Gargi Das1, Prateek Bhatia2, Naveen Sankhyan1,  
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

Correspondence Address:
Naveen Sankhyan
Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012

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;69:1456-1458

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 2022 Jan 23 ];69:1456-1458
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Full Text


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}

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}{Figure 3}

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.


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