PracticeUpdate Conference Series_WORLDSymposium 2019

PatientsWithMPS IIWithout Cognitive Impairment Still MarkedlyAffected by Somatic Symptoms The disease inflicts somatic P atients who suffer from mucopolysaccharidosis (MPS) II without cognitive impair- ment remain markedly affected by somatic symptoms. Despite the absence of cognitive impairment, the disease inflicts somatic symptoms, reports a survey. Heather Lau, MD, of New York University, and colleagues used data from the Hunter Outcome Survey registry to examine the age at which an absence of cognitive impair- ment might indicate non-neuropathic disease. symptoms regardless of an absence of cognitive impairment.

Examination of cognitive data in the Hunter Outcome Survey (answer to a yes/no question based on clinical impression and/or standardized testing) by age revealed that changes in cognitive status were infrequent after a cut-off age of 10 years. Using this criterion, they compared clinical characteristics of patients with neuronopathic and non-neuronopathic MPS II. Of 146 patients (2 females) whose cognitive assessment was available at age 10 years and who had attended at least one follow-up assessment at age ≥11 to <20 years, 127 (87.0%) exhibited no change in cognitive status between these assessments. At age 10 years, 80/127 (63.0%) patients exhibited cognitive impairment and 47/127 (37.0%) no cognitive impairment. Median age at the last visit was 13.8 (range 11.8, 18.0) and 14.8 (range 11.9, 19.5) years, respectively. Symptom onset occurred earlier in patients with cognitive impairment (1.5 [range 0.3–3.0] vs 2.3 [range 0.5–4.5] years). The most common signs and symptoms were similarly prevalent in each group. Though not among the most prevalent manifestations, bladder/urinary incontinence, enlarged tongue, behavioral problems, and sleep apnea were more common in patients with cognitive impairment. The number of surgeries by age 10 years (3 [range 1–8] vs 4 [range 1–8]), age at first surgery (2.3 [range 0.2–6.8] vs 2.3 [range 0.2–5.1] years) and types of surgery were also similar. Dr. Lau explained that patients with neuronopathic MPS II (Hunter syndrome) develop progressive cognitive impairment, whereas those with non-neuronopathic disease remain cognitively intact. All patients experience somatic involvement, the extent of which varies widely. Cognitive decline is often apparent by age 5 years, though this decline also varies. The estimated one-third of patients with MPS II suffer from the non-neuronopathic form, though more likely to have normal cognitive abilities, may experience other neurological disorders related to accumulation of glycosaminoglycans (for example, seizures, carpal tunnel syndrome, myelopathy) in addition to somatic symptoms. However, somatic symptoms are life-limiting, and such patients usually die in early adulthood. Other fndings in both forms of MPS II include short stature; macrocephaly with or without communicating hydrocephalus; macroglossia; hoarse voice; conductive and sensorineural hearing loss; hepatosplenomegaly; dysostosis multiplex; spinal stenosis; and carpal tunnel syndrome. MPS II is an X-linked disorder. Though variable in age of onset and severity, males inheriting the X-linked gene mutation are always affected. Females who inherit the gene for MPS II disease are not expected to be symptomatic. Sons born to carrier females are at a 50% risk of being affected. Daughters are at 50% risk of being a carrier, like their mother. Affected males will not pass the X-linked gene mutation to any of their sons, but 100% of their daughters will be carriers of the X-linked MPS II disease. Dr. Lau concluded that the data indicate that patients with MPS II without cognitive impairment are still markedly affected by somatic symptoms of the disease. She told Elsevier’s PracticeUpdate , “This disease exerts a signifcant impact on themorbidity of patients with and without cognitive impairment. Both groups, therefore, warrant frequent surveillance and intervention for complications of this multisystemic disease. Early initiation of treatment with recombinant idursulfase should be considered for both groups.”

" Though not among the most prevalent

manifestations, bladder/urinary incontinence, enlarged tongue, behavioral problems, and sleep apnea were more common in patients with cognitive impairment. "

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WORLDSymposium 2019 • PRACTICEUPDATE CONFERENCE SERIES 17