Mucopolysaccharidosis Type 2, Severe 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 (MPS2, see this term), severe form (MPS2S), is associated with a massive accumulation of glycosaminoglycans and a wide variety of symptoms including a rapidly progressive cognitive decline; it is most often fatal in the second or third decade.

Epidemiology

Prevalence of MPS2 at birth in Europe is 1/166,000, the severe form accounts for at least two-thirds of all cases.

Clinical description

MPS2S presents with the spectrum of symptoms observed in all MSP2 (see this term) cases, often with an earlier presentation. MPS2S patients have a decrease in growth rate in early to mid-childhood, along with respiratory difficulties and a thickening of lips and nostrils as well as an enlarged and protruding tongue (distinctive facies), which may become evident between 2-4 years of age. Psychomotor milestones are delayed, and regression often occurs. Between the ages of 2-6 years patients begin to exhibit aggressive behavior and hyperactivity, often lacking any sense of danger as they follow a course of progressive cognitive decline. Vision may be affected, and progressive hearing loss occurs in most cases. Myocardial thickening and cardiac valve dysfunction are common. Approximately 60-80 % of patients with MPS2 have the severe form of the disease with neurological implications.

Etiology

MPS2 results from iduronate-2-sulfatase (I2S) deficiency, which leads to lysosomal accumulation of two specific mucopolysaccharides, dermatan sulfate and heparan sulfate. MPS2S appears to be associated with a complete absence of functional enzyme due to nonsense mutations or complete gene deletions or rearrangements. In most cases, however, prognosis cannot be established by genotype alone.

Diagnostic methods

Diagnosis is based on detection of increased levels of DS and HS in the urine and confirmed by the demonstration of the enzyme deficiency in the serum, leukocytes or fibroblasts, or in dried blood spot samples. Enzymatic activity of another sulfatase should also be assessed. Genetic testing is possible; sequencing must include the entire IDS gene including its promoter region.

Management and treatment

Regular evaluation of patients should be followed by palliative care as is necessary. Cranial shunting to relieve hydrocephalus is often required. Weekly intravenous infusion with recombinant enzyme preparations has been shown to help with somatic symptoms. Intrathecal administration of enzyme replacement therapy holds promise to treat neurological aspects of MSP2; testing of such treatments is ongoing.

Prognosis

Prognosis is poor. MPS2S is most often fatal within the second or third decade of life, due to obstructive airway disease, infection, or cardiac failure due to valve dysfunction, pulmonary hypertension or cardiomyopathy.