Alexander Disease

Alexander disease (AD) is a progressive disorder of the white matter of the central nervous system (CNS). The three types of AD are categorized by age of onset: infantile, juvenile, and adult. Affected infants develop a megalencephalic leukodystrophy, seizures, spasticity, ataxia, and psychomotor retardation. Infantile AD frequently leads to death within a decade after the diagnosis. Juvenile and adult forms of AD have a more slowly progressive course and are characterized by ataxia, bulbar signs and spasticity. Rosenthal fibers, observed in the astrocytes of affected individuals upon autopsy, are a hallmark feature of AD. These cytoplasmic inclusions are made up of glial acidic fibrillary protein (GFAP) and small heat-shock proteins. MRI has proven to be a useful tool for diagnosing AD, and often shows high signal intensity of white matter in the frontal area and basal ganglia. Alexander disease is usually sporadic and is most often caused by de novo heterozygous mutations in the GFAP gene. The recurrence risk, even when both parents are negative for GFAP mutations, is unknown and may thus warrant consideration of prenatal diagnosis for couples who have had an affected child. There is one report of a clinically-diagnosed Alexander disease patient with apparent autosomal recessive mutations in the NDUFV1 gene.

Tests Available

Forms and Documents

Test Info Sheet Test Requisition

Test Details

  • Confirmation of a clinical diagnosis
  • Differentiation of Alexander disease from Canavan disease
  • Prenatal diagnosis in at-risk pregnancies

Ordering

218
3 weeks
2-5 mL Blood - Lavender Top Tube
Dried Blood Spots | Buccal Swabs

*Reporting times are typical, but could be extended in situations outside GeneDx's reasonable control.

Billing

81405x1
No
Yes
  • 330 Cerebral degenerations usually manifest in childhood Use additional code to identify associated mental retardation
  • 742.4 Other specified anomalies of brain, Congenital cerebral cyst, Macroencephaly, Macrogyria, Megalencephaly, Multiple anomalies of brain NOS, Porencephaly Ulegyria
  • 330.8 Other specified cerebral degenerations in childhood, Alpers' disease or gray-matter degeneration, Infantile necrotizing encephalomyelopathy, Leigh's disease, Subacute necrotizing, encephalopathy or encephalomyelopathy
For price inquiries please email zebras@genedx.com

**The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

References

  1. Schuelke, M et al., Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy. Nat Genet 21(3):260-1. 1999
  2. Brenner, M et al., Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease Nature Genetics 27:117-120 (2001)
  3. Meins M et al., Infantile Alexander Disease: A GFAP Mutation in Monozygotic Twins and Novel Mutations in Two Other Patients Neuropediatrics 33:194-198 (2002)
  4. Rodriguez D et al., Infantile Alexander Disease: Spectrum of GFAP Mutations and Genotype-Phenotype Correlation Am J Hum Genet 69:1134-1140 (2001)
  5. Gorospe JR et al., Molecular findings in symptomatic and pre-symptomatic Alexander disease patients Neurology 58: 1494-1500 (2002)

Forms and Documents

Fact Sheet Gene List Test Requisition Test Info Sheet Family Member Test Requisition

Test Details

AARS, AARS2, ABAT, ABCD1, ACADS, ACER3, ACOX1, ACY1, ADAR, ADGRG1, ADSL, AHDC1, AIMP1, ALDH3A2, ALDH6A1, AMN, AMPD2, ANK3, AP4B1, AP4S1, APOPT1, ARHGAP31, ARHGEF10, ARNT2, ARSA, ASNS, ASPA, ASXL1, AUH, BCAP31, BCS1L, BEST1, BMP4, BRAT1, CARS2, CCDC88A, CHMP2B, CLCN2, CLN6, CLP1, COL4A1, COL4A2, COX10, COX15, COX7B, CPLX1, CSF1R, CTBP1, CTC1, CTDP1, CYP27A1, CYP7B1, D2HGDH, DAG1, DARS, DARS2, DDHD2, DEAF1, DHFR, DHH, DLL4, DNM2, DOCK6, DPYS, DYRK1A, EARS2, EDNRB, EGR2, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, ENTPD1, EOGT, ERCC2, ERCC6, ERCC8, FA2H, FAM126A, FBXL4, FGD4, FGFRL1, FIG4, FKRP, FOXC1, FOXG1, FOXRED1, GAA, GALC, GAN, GBE1, GCDH, GDAP1, GFAP, GFM1 (EFG1), GJA1, GJB1, GJC2, GLB1, GLUL, GLYCTK, GNAO1, GRM7, GRN, HEPACAM, HEXA, HSD17B4, HSPD1, HTRA1, IBA57, IDUA, IER3IP1, IFIH1, ISCA2, ITPA, KARS, KCNJ10, KCNT1, L2HGDH, LAMA1, LAMA2, LAMB1, LARGE1, LETM1, LIPT1, LITAF, LMNB1, LRPPRC, LYRM7, MAPT, MARS2, MAT1A, MCOLN1, MEF2C, MLC1, MOCS1, MOCS2, MPV17, MPZ, MRPS22, MTFMT, MTTP, MUT, NADK2, NDRG1, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA2, NDUFA9, NDUFAF2, NDUFAF3 (C3ORF60), NDUFAF4 (C6ORF66), NDUFAF5, NDUFAF6, NDUFB3, NDUFB9, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NDUFV3, NEFL, NFU1, NGLY1, NOTCH1, NOTCH3, NRXN1, NSD2, NUBPL, OCRL, PAFAH1B1, PC, PCDH12, PDYN, PEX1, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6, PEX7, PGAP1, PHGDH, PHYH, PIGA, PLEKHG2, PLP1, PMP22, POLG, POLR1C, POLR3A, POLR3B, POMK, POMT1, PPP2R1A, PRKDC, PRPS1, PRX, PSAP, PSEN1, PTEN, PURA, PYCR2, QARS, RARS, RBPJ, RMND1, RNASEH2A, RNASEH2B, RNASEH2C, RNASET2, RNF216, RPIA, RPS6KC1, SAMHD1, SBF2, SCP2, SDHA, SDHAF1, SDHB, SDHD, SEPSECS, SH3TC2, SHANK3, SHPK, SLC16A2, SLC17A5 , SLC1A4, SLC25A1, SLC25A12, SLC25A22, SLC33A1, SLC35A2, SLC46A1, SLC6A8, SNIP1, SOX10, SPATA5, SPG11, SPG20, SPTAN1, SQSTM1, SSR4, STAMBP, STAT1, STXBP1, SUMF1, SURF1, SYNE1, TACO1, TAF2, TARS2, TM4SF20, TMEM126B, TMEM165, TMEM187, TMEM70, TRAPPC9, TREM2, TREX1, TRMT10A, TRMT5, TSC1, TSEN54, TUBB2A, TUBB4A, TUFM, TYMP, TYROBP, UBE2A, UPB1, VARS2, VCP, VPS11, WWOX, ZEB2, ZFYVE26, ZNF335
  • Molecular confirmation of a clinical diagnosis
  • To assist with decisions about treatment and management of individuals with leukodystrophy or leukoencephalopathy
  • Testing of at-risk relatives for specific known variant(s) previously identified in an affected family member
  • Prenatal diagnosis for known familial pathogenic variant(s) in at-risk pregnancies

Ordering

J853
6 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swabs

*Reporting times are typical, but could be extended in situations outside GeneDx's reasonable control.

Billing

81404x5, 81405x6, 81406x5, 81401x1
Yes
Yes
For price inquiries please email zebras@genedx.com

**The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

References

  1. Vanderver A et al. Leukodystrophy Overview. 2014 Feb 6. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: https://www.ncbi.nlm.nih.gov/books/NBK184570/.
  2. Bonkowsky et al. (2010) Neurology 75 (8):718-25 (PMID: 20660364)
  3. Heim P, Claussen M, Hoffmann B, Conzelmann E, Gärtner J, Harzer K, Hunneman DH, Köhler W, Kurlemann G, Kohlschütter A. Leukodystrophy incidence in Germany. Am J Med Genet. 1997;71:475–8 (PMID: 9286459).
  4. Zou et al. Whole exome sequencing: an effective and comprehensive genetic testing approach for leukodystrophy [abstract submitted] To be presented at the 2017 ASHG Annual Genetics Meeting, October 17-21, Orlando, FL.