Mucopolysaccharidosis Type 2, Attenuated Form

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

IDS, ARSH, IDS2, TFRC, IDUA, LINC00893, MPEG1, TTK, RPS27, F9, FMR1, IDSP1, ABCB6, CD38, FOXG1, SLC35G1, ARNTL2, DESI1, CLOCK, L1CAM, PER2, AFF2, CD34, PER1, CD99, CANX

Drugs

Adeno-associated viral vector serotype 2/6 encoding zinc-finger nucleases and the human iduronate 2-sulfatase gene, Adeno-associated viral vector serotype 9 containing the human iduronate-2-sulfatase gene, Allogeneic multi-virus specific T lymphocytes targeting BK virus, cytomegalovirus, human herpesvirus-6, Epstein Barr virus and adenovirus, Humanised IGg1 monoclonal antibody targeting human transferrin receptor conjugated to human iduronate-2-sulfatase, Idursulfase ( ELAPRASE ), Recombinant human insulin receptor monoclonal antibody-fused iduronate 2-sulfatase ( HIRMAb-IDS), haematopoietic stem cells and blood progenitors umbilical cord-derived expanded with (1R, 4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide dihydrate

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Mucopolysaccharidosis type 2, attenuated form (MPS2att), the less severe form of MPS2 (see this term), leads to a massive accumulation of glycosaminoglycans and a wide variety of symptoms including distinctive facies, short stature, cardiorespiratory and skeletal findings. It is differentiated from mucopolysaccharidosis type 2, severe form (see this term) by the absence of cognitive decline.

Epidemiology

Prevalence of MPS2 at birth in Europe is 1/166,000. The minority of these cases present with the attenuated form.

Clinical description

MPS2att is clinically heterogeneous and its rate of progression is highly variable. Patients appear healthy at birth, with subtle initial symptoms appearing between 18 months and 4 years of age or even later, in particular umbilical or inguinal hernia. A distinctive facies (thickening of lips and nostrils, enlarged and protruding tongue), forms slowly and may first be observed at 2-4 years of age (often not evident until late). Swelling of the upper respiratory tract may be responsible for frequent infections, in particular otitis media; excessive snoring and sleep apnea; a distinctive hoarse voice and progressive loss of hearing. During early childhood growth is stunted and patients have a short stature with dysostosis multiplex and stiff joints that may make movement painful, hip dysplasia may also occur. Phalangeal joints are universally contracted resulting in claw-like hands; carpal tunnel syndrome is common. Spastic paresis due to spinal cord compression at the cranio-cervical region may also occur. Pressure exerted on the optic nerve may lead to loss of vision and retinal degeneration has also been reported in some cases. MPS2att patients, in general, have no cognitive impairments.

Etiology

MPS2 results from iduronate-2-sulfatase (I2S) deficiency, which leads to lysosomal accumulation of two specific mucopolysaccharides, dermatan sulfate and heparan sulfate. MPS2att, is typically associated with missense mutations of the causative gene IDS (Xq28), e.g.: c.1122C>T. In 12 cases of affected girls, skewed X inactivation led to MPS2.

Genetic counseling

MPS2 is the only MPS transmitted as an X-linked recessive trait; female carriers transmit the disorder to 50% of their sons.

Management and treatment

Extensive palliative care is required, patients must be regularly evaluated by echocardiogram, respiratory function, hearing tests, eye exams, nerve conduction velocity tests, cranial and cervical MRI with or without lumbar puncture to assess cerebrospinal fluid pressure. Hernia repair, tonsillectomy and adenoidectomy may be required. Cardiac valve or hip replacement and carpal tunnel release may be necessary in MPS2att patients over time; patients should be considered for weekly intravenous enzyme replacement therapy with idursulfase (Elaprase) as early as possible.

Prognosis

In general, if patients have no evidence of cognitive involvement by about 5 years of age, it is most likely that they will develop only the attenuated form of MPS2. Prognosis is highly variable. In most attenuated cases patients live into adulthood and require limited palliative care, however, it is impossible to predict outcomes due to the great variability of disease progression from patient to patient, even when siblings carry an identical mutation.