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IDNS
80945
Clinical Information: Adult World Health Organization (WHO) grade II and III astrocytomas,
oligodendrogliomas and oligoastrocytomas, and secondary glioblastomas (GBM) have been shown to
harbor IDH1 and IDH2 mutations.(1-5) These missense mutations most frequently involve the arginine
amino acid at IDH1 position 132 (R132) and at IDH2 position 172 (R172). The most frequent IDH1
amino acid alteration accounting for over 90% mutations is R132H, in addition to R132C, R132S,
R132G, R132L, and R132V.(1) For IDH2, R172K, R172G, R172M, and R172W mutations have also
been reported.(4,5) IDH proteins are nicotinamide adenine dinucleotide phosphate (NADP)-dependent
isocitrate dehydrogenases that catalyze the oxidative decarboxylation of isocitrate to produce
alpha-ketoglutarate. IDH1 and IDH2 mutations appear to be an early event in the development of these
tumors and impair the enzyme activity,(3-4) resulting in loss of the ability to catalyse conversion of
isocitrate to alpha-ketoglutarate. However, the enzyme acquires a neomorphic activity and is able to
catalyze the NADPH-reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). These mutations
appear to have prognostic significance with increased overall survival(1,4) and have been found to be
associated with a younger age among adult diffuse astrocytomas, WHO grade III astrocytomas,(4) and
GBM patients.(1-3) Of note, IDH1 mutations are only rarely reported among pilocytic astrocytomas,(2-4)
primary GBM,(1,2) supratentorial primitive neuroectodermal tumors,(2) and pleomorphic
xanthoastrocytomas,(4) and are absent in pediatric diffuse astrocytomas, ependymomas,
medulloblastomas, primitive neuroectodermal tumors, and dysembryoblastic tumors.(3,4)
Useful For: Supporting a diagnosis of grade II or III astrocytoma, oligodendroglioma,
oligoastrocytoma, or secondary glioblastoma Stratifying prognosis of gliomas
Interpretation: The presence of an IDH1 or IDH2 mutation supports a diagnosis of grade II or III
astrocytoma, oligodendroglioma, oligoastrocytoma, or secondary glioblastoma (GBM) in the context of
other corroborating pathologic features. IDH1 codon 132 and IDH2 codon 172 mutations have been
identified in more than 70% of brain tumors diagnosed as grade II and III astrocytoma,
oligodendroglioma, oligoastrocytoma, and secondary GBM. These mutations are rarely found in other
brain tumors and nonbrain tumors. The ordering physician is responsible for the diagnosis and
management of disease and decisions based on the data provided. A negative result does not exclude the
presence of a brain tumor.
Reference Values:
Negative
Clinical References: 1. Parsons DW, Jones S, Zhang X, et al: An integrated genomic analysis of
human glioblastoma multiforme. Science 2008;321:1807-1812 2. Balss J, Meyer J, Mueller W, et al:
Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 2008;116:597-602 3.
Ichimura K, Pearson DM, Kocialkowski S, et al: IDH1 mutations are present in the majority of common
adult gliomas but rare in primary glioblastomas. Neuro Oncol 2009;11:341-347 4. Yan H, Parsons DW,
Jin G, et al: IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009;360:765-773 5. Hartmann C,
Meyer J, Balss J, et al: Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and
oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol
2009;118:469-474
Iduronate Sulfatase, Fibroblasts
Clinical Information: Mucopolysaccharidosis II, (MPS II, Hunter syndrome) is an X-linked
lysosomal storage disorder caused by the deficiency of iduronate sulfatase (IDS). The
mucopolysaccharidoses are a group of disorders caused by the deficiency of any of the enzymes involved
in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate
(glycosaminoglycans [GAGs]). Accumulation of GAGs (previously called mucopolysaccharides) in
lysosomes interferes with normal functioning of cells, tissues, and organs. MPS II is caused by a reduced
or absent activity of the IDS enzyme and gives rise to the physical manifestations of the disease. Clinical
features and severity of symptoms of MPS II are widely variable ranging from severe disease to an
attenuated form, which generally presents at a later onset with a milder clinical presentation. In general,
symptoms may include coarse facies, short stature, enlarged liver and spleen, hoarse voice, stiff joints,
cardiac disease, and profound neurologic involvement leading to developmental delays and regression.
Unlike MPS I (Hurler syndrome), corneal clouding is not typically present. Because MPS II is an
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