|Year : 2022 | Volume
| Issue : 3 | Page : 67-69
Siblings with Scheie syndrome
Meenu Anna Varghese, Jo Martin Kuncheria, KN Poornima, Anu Marie Peter
Department of Pediatrics, Govt. TD Medical College, Alappuzha, Kerala, India
|Date of Submission||31-Mar-2023|
|Date of Decision||09-May-2023|
|Date of Acceptance||16-May-2023|
|Date of Web Publication||29-Aug-2023|
Dr. Meenu Anna Varghese
Department of Pediatrics, Govt. TD Medical College, Alappuzha, Kerala
Source of Support: None, Conflict of Interest: None
Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders. Mucopolysaccharidosis type 1 (MPS-1) results from mutation of the IUA gene on chromosome 4p encoding alpha-L-iduronidase. Clinical features vary from severe Hurler-to-mild Scheie syndrome. A 10-year- and 10-month-old boy, born as the third child of nonconsanguineous marriage presented with opacity of bilateral cornea as well as restricted movements and progressive deformity of the spine, bilateral upper limb and lower limb since birth. History of right inguinal hernia repair at 1 year, B/L carpel tunnel surgery at 8 years, and right lamellar keratoplasty at 9 years. H/o repeated upper respiratory infection present. History of fever triggered seizures at 1.6 years and 2 years. Gives h/o delay in attainment of motor milestones. Presently he has poor scholastic performance with difficulties in writing, learning and performing mathematical calculations. Hearing assessment done was normal. Right eye near vision was 20/100 distance equivalent. The left eye showed light perception only. His 13-year-old sibling who has similar complaints since birth. General examination shows coarse facies with corneal clouding, contracture, and deformity of multiple joints. Anthropometry shows underweight and short stature. Hepatosplenomegaly was present. Routine blood investigations were within normal limits. He had a urine MPS screening done at 3 years of age which was positive for MPS-1 and the diagnosis was confirmed based on nucleic acid isolation later at 6.6 years of age. Echocardiogram done was normal. The child was diagnosed to have MPS-1. He was managed by multidisciplinary approach including Recombinant enzyme replacement therapy and medical and surgical treatment for his disabilities.
Keywords: Contracture and deformity, corneal clouding, mucopolysaccharidoses
|How to cite this article:|
Anna Varghese M, Kuncheria JM, Poornima K N, Peter AM. Siblings with Scheie syndrome. Pediatr Companion 2022;1:67-9
| Introduction|| |
Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders that are inherited as autosomal recessive disorders except mucopolysaccharidosis type 2 (MPS-2) which is inherited as X-linked recessive. Clinical features of mucopolysaccharidosis type 1 (MPS-1) vary from severe Hurler-to-mild Scheie syndrome. MPS-1 occurs due to the mutation in the IUA gene on chromosome 4p16.3, which encodes for alpha-L-iduronidase. MPS are glycosaminoglycans that are complex carbohydrates composed of uronic acids, amino sugars, and neutral sugars. Accumulation of these complex carbohydrates occurs in the arteries, skeleton, eyes, joints, ears, skin, teeth, liver, spleen, central nervous system, blood, and bone marrow. This accumulation eventually causes progressive damage to cells, tissues, and various organ systems of the body.
| Clinical presentation|| |
A 10-year and 10-month-old boy, third child of nonconsanguineous marriage, presented with complaints of corneal opacity noticed since birth with a progressive decrease in vision and restriction of movements of multiple joints with progressive deformity of the spine, upper limbs, and lower limbs since 6 years of age. The antenatal period was uneventful. The mother noticed opacity of the cornea in the initial days after birth but considered it normal and did not follow it up further. The opacity of the cornea was detected by doctors during an inguinal hernia repair done at 1 year of age but no interventions were done for the same. The child had a history of recurrent upper respiratory tract infections since infancy which were managed on an outpatient basis. He had a history of fever-triggered seizures at 1.6 years and 2 years of age but no detailed evaluation was done. Ophthalmology consultation was done at 3 years and the child was referred to pediatrics, admitted and evaluated, and diagnosed to have MPS-1 (elevated urine glycosaminoglycans). Right lamellar keratoplasty was done at 9 years of age. There was a history of delay in attainment of motor milestones and was advised physiotherapy for the same; however, they were lost to follow-up. There was a history of surgery for bilateral carpel tunnel syndrome at 8 years of age. At present, the child has average writing skills, and below average mathematical and learning skills. The hearing assessment was normal. Near vision in the right eye was 20/100 distance equivalent. The left eye showed the perception of light only. He has two brothers, 13 and 15 years old with the 13-year-old also being diagnosed with MPS-1. On general examination, vitals were stable. On head-to-foot examination [Figure 1], his head appeared large for age, he had bilateral corneal clouding sparing the right central portion [Figure 2], depressed nasal bridge, low set and prominent ears bilaterally, retrognathia, macroglossia, high arched palate, widely spaced teeth, widely spaced nipple, protuberant abdomen, umbilical hernia, exaggerated lordosis and contractures and flexion deformity of multiple upper and lower limb joints [Figure 3]. He was underweight and had short stature by anthropometry. Systemic examination showed moderate hepatosplenomegaly
| Investigation|| |
Routine blood investigations done were within normal limits. Urine MPS screen done at 3 years of age was positive for MPS-1, which was later confirmed by nucleic acid isolation at 6.6 years of age. Echocardiogram done was normal.
| Discussion|| |
This child was diagnosed to have MPS-1 with a similar history in one of his siblings. His clinical features were consistent with Scheie syndrome. Scheie syndrome is a mild disease characterized by corneal clouding, glaucoma, retinal degeneration, joint contractures, and mild dysostosis with no intellectual disability. Aortic valve disease is common in these children. MPS-1 is usually diagnosed after 5 years of age. Carpel tunnel syndrome is a common associated finding. They usually have airway problems. Skeletal survey shows features of dysostosis. Urine shows elevated excretion of glycosaminoglycans. Definitive diagnosis is by enzyme assay in serum, leucocytes, and cultured fibroblasts. Molecular analysis is done by appropriate gene panels. Newborn screening can be done by dried blood spot analysis. Differential diagnoses include Mucolipidoses and oligosaccharides that have a similar clinical picture but the urinary elevation of glycosaminoglycans is absent in these conditions. All patients with MPS-1 should receive a comprehensive baseline evaluation, including neurologic, ophthalmologic, auditory, cardiac, respiratory, gastrointestinal, and musculoskeletal assessments, and should be monitored every 6–12 months with individualized specialty assessments, to monitor disease progression and effects of the intervention. Treatment options include symptomatic therapy, hematopoietic stem cell transplantation, and enzyme replacement therapy. Here the siblings were managed by a multispecialty and multidisciplinary approach including symptomatic therapy and recombinant enzyme replacement therapy. Both siblings were currently receiving IV Aldurazyme infusion weekly.
| Prognosis|| |
There is no cure for MPS. Hurler type is a severe progressive disease with cardiac anomalies, hearing loss, and other system involvement with a life expectancy of 10 years. Scheie syndrome is the milder form with a higher life expectancy. Enzyme replacement therapy can significantly reduce hepatomegaly, promote growth, decrease joint restriction, lessen sleep apnea, and improve breathing in individuals with intermediate and Scheie MPS-1.Hematopoietic stem cell transplant increases survival, reduces facial coarseness and hepatosplenomegaly, improves hearing, and preserves normal heart function. Because the recombinant enzyme is not thought to cross the blood–brain barrier, the best option to reduce the risk of cognitive impairment remains early hematopoietic stem cell transplant (before 2 years). A standard of care for the treatment of patients with MPS-1 will optimize clinical outcomes and patient’s quality of life.
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kliegman RM Nelson textbook of pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020; p. 811.
Lysosomal storage support society, What is Mucopolysaccharidosis (MPS)? Available from: https://lsdssindia.org/about-lsds/mucopolysaccharidosis/
Muenzer J, Wraith JE, Clarke LA Mucopolysaccharidosis I: Management and treatment guidelines. Pediatrics 2009; 123:19-29.
[Figure 1], [Figure 2], [Figure 3]