Year : 2016 | Volume
: 9 | Issue : 4 | Page : 534--536
Mental health perspectives of Hunter syndrome: Case reports of two biological siblings
Kabir Garg, Sujita Kumar Kar
Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India
Sujita Kumar Kar
Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh
Hunter syndrome is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase, leading to progressive accumulation of a substance called glycosaminoglycans in nearly all cell types, tissues, and organs. Hunter syndrome presents with facial dysmorphism, airway diseases, skeletal defects, cardiomyopathies, and neuropsychiatric manifestations. Mental subnormality is a cardinal feature in Hunter syndrome. This is a progressive cognitive decline that is not amenable to enzyme replacement therapy. Due to progressive cognitive decline, training the children to improve the adaptive functioning is a challenge that creates immense stress for the caregivers. Patients with Hunter syndrome should undergo serial assessment of intellectual ability and may be trained accordingly.
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Garg K, Kar SK. Mental health perspectives of Hunter syndrome: Case reports of two biological siblings.Med J DY Patil Univ 2016;9:534-536
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Garg K, Kar SK. Mental health perspectives of Hunter syndrome: Case reports of two biological siblings. Med J DY Patil Univ [serial online] 2016 [cited 2020 Sep 22 ];9:534-536
Available from: http://www.mjdrdypu.org/text.asp?2016/9/4/534/186068
Hunter syndrome, also known as mucopolysaccharidosis Type II (MPS II), is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase, leading to progressive accumulation of a substance called glycosaminoglycans (GAGs) in nearly all cell types, tissues, and organs.
Clinical manifestations include facial dysmorphism, airway diseases, skeletal defects, cardiomyopathies, and neuropsychiatric manifestations. As there is no effective therapy for MPS Type II (Hunter syndrome), care has been predominantly palliative. However, enzyme replacement therapy (ERT) with recombinant human iduronate-2-sulfatase has now been introduced.
We highlight here, the mental health aspects of two biological siblings with Hunter syndrome (with specific emphasis on the challenges in training these children with progressive cognitive decline and burden of care on their caregivers).
Master A and Master B, two biological siblings of ages 11 and 5 years, respectively, from a middle socioeconomic background, were referred for psychiatric evaluation including assessment of intellectual ability. History revealed no adverse antenatal or perinatal events. They, however, had a history of delayed milestones and impaired adaptive functioning. Family history was noncontributory. The subjects had two sisters with no apparent physical or behavioral abnormalities.
Both the children had a history of recurrent respiratory infections and intermittent joint pain since early childhood.
On examination, they had short stature, big head, protruding abdomen, coarse skin, swollen wrist joints, and clubbed fingers. They also had characteristic features of Hunter syndrome such as stunted growth, coarse facial features (large forehead, thick neck, tongue and lips, bushy eyebrows, and flattened nose), hearing loss, joint stiffness, poor peripheral vision, thickening of the heart valves, and hepatosplenomegaly.
The siblings had been investigated; their enzyme assay tests documented the deficient activity of iduronate-2-sulfatase. The pure tone audiometry of elder sibling detected profound sensorineural hearing loss, whereas the younger sibling had a moderate sensorineural hearing loss. The echocardiogram of revealed mild mitral regurgitation with thickened anterior mitral leaflet and cleft mitral leaflet in the elder sibling, while the younger one had similar presentation along with mild aortic stenosis. Skiagrams revealed that both siblings had abnormal metacarpals with cupping of distant metaphysis, bullet-shaped phalanges, irregular metaphysical margins of tibia and fibula, calvarial thickening with a “J”-shaped sella, and anterior beaking of cervical vertebral bodies. The elder sibling had scalloping of anterior surface of lumbosacral vertebral bodies and biconvex margins. The younger sibling had no such abnormalities. Assessment of their intellectual functioning revealed an intelligence quotient (IQ) of 50-55 for the elder sibling and 80-85 in the younger one.
Patients with Hunter syndrome typically appear normal at birth, as seen in our cases. In the severe form of Hunter syndrome, clinical features appear between 2 and 4 years of age, whereas in the mild form, the clinical features appear in the second decade of life.,,,, The symptoms in our cases had appeared in the early life, pointing toward a possibility of severe subtype in these children and a poor life expectancy. In the severe form, there is severe mental retardation and loss of skills. Death usually occurs in the first or second decade of life, and the main cause of death is obstructive airway disease or cardiac failure. In the milder form, there is mild mental retardation, stature is near normal, the clinical features are less obvious and progress very slowly. Diagnosis is usually made in the second decade of life. Death usually occurs in the fourth decade, and the main cause of death is cardiac failure.,,,, In our cases, although the younger sibling did not have mental retardation, both the siblings had an array of structural and cardiac defects, also of note was the significantly poor intellectual performance of the elder sibling when compared with the younger one, and the history of loss of learned skills in the elder sibling over the previous years hinting toward a progressive cognitive decline. Communicating hydrocephalus is a common finding in Hunter's syndrome and can lead to severe manifestation of neurological signs, which however, were not present in our cases.
Analysis of GAGs (heparan and dermatan sulfates) is a screening test for MPS Type II. The presence of excess heparan and dermatan sulfates in the urine is suggestive of MPS Type I, MPS Type II, or MPS Type VII. Confirmatory diagnosis is made by enzyme assay in leukocytes, fibroblasts or dried blood spots, and plasma sample, using substrates specific for iduronate-2-sulfatase. Absent or low iduronate-2-sulfatase activity in males is diagnostic of Hunter syndrome, provided other sulfatase deficiency has been ruled out.
ERT using a recombinant human iduronate-2-sulfatase produced in the human cell line has been recently approved for the management of MPS Type II. Bone marrow transplantation and umbilical cord blood transplantation are definitive treatments for MPS. Apart from these, supportive management is very important. Physical therapy and daily exercise may improve the mobility of joints. Blood transfusion, infection, and nutritional management are also important in the management of MPS Type II.
All these things, however, take a separate dimension when it comes to resource-poor setups in a developing country such as ours. The definitive treatment of Hunter sydrome is beyond the affordability of common people. Frequent medical complications often adds to the financial burden as well as stress of the caregivers. There is also the attached stigma and the loss of social stature and esteem associated with the “abnormal child” where some archaic societies view them as a manifestation of God's Wrath or results of wrong doings by the parents. Many times, in predominant patriarchal societies, the “blame” for this is put on the mothers. All these factors, along with the highly demanding care of such kids put a lot of stress on the caregivers and cause relation emotional and psychological problems.
Mental subnormality is a very common finding in metabolic disorders such as Hunter syndrome. Progressive cognitive decline, associated with Hunter syndrome, is not amenable to the ERT due to the nonpenetrance of blood brain barrier to the large protein molecules. Thus, even on training, a good functionality level might not be achieved, as is otherwise possible in patients of isolated intellectual disability. In the IQ Assessment carried out at our set-up, the younger sibling performed far better than the older sibling with a functional IQ of 80-85 (low average intelligence), as compared to 50-55 of the older sibling, which falls in the ambit of mild mental retardation. It was advised to repeat IQ assessments in the follow-up to monitor the progressive intellectual decline.
While the physical effects and the sufferings of a patient with Hunter's syndrome and his parents are well-known; there are many effects on the adaptive function and quality of life. The impact on caregivers has also been studied, and they have been found to be suffering from discontentment and distress, especially with respect to the time, they had for their own needs, due to their children's condition.
The families of patients with MPS II require considerable psychological and social support, as well as motivation. The clinicians are expected to provide answers to not only treatment-related questions but also to questions regarding the future prospects of these patients. A pivotal role in this field have been played by the patient societies that provide counseling's to family members, making them aware of the disability benefits as well as financial helps, available from various sources. They work in proximity with the physicians, families, and government agencies to make treatment available to the needy. For example, in the United Kingdom, the society for mucopolysaccharide diseases plays a very important role in matching patients with enzyme replacement trials and supporting the families in investigations and in coping with the situations.
Mental health needs in cases with Hunter syndrome can be addressed by serial evaluation of intellectual abilities and comorbidities. Simultaneously, the mental health needs of the caregivers should be addressed adequately, who face a lot of challenges in terms of caring, training as well as seeking help for several serious comorbidities with Hunter syndrome.
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Conflicts of interest
There are no conflicts of interest.
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