© 2018 The Brooks Coleman White Foundation, Inc.

DISEASE INFO

Leukodystrophy is a rare group of neurodegenerative diseases that affect the white matter of the brain.  These diseases are genetic, progressive, and currently have no cure.  The genetic abnormalities of leukodystrophy cause the irregular development of nerves' myelin sheath, which acts as a protective barrier to the nerves themselves.  Without the healthy development of the myelin sheath, the nerve cells have difficulty sending and receiving electrical signals.  Essentially, this abnormal development causes "exposed wiring" in the brain, significantly affecting the central nervous system's functionality.

Each form of leukodystrophy is directly linked to a specific genetic abnormality, which causes the degradation (or in some cases the overproduction) of the myelin sheath.  While much is known about the genetic causes and clinical features of the multiple types of leukodystrophy, the rarity of the diseases has led to limited awareness and research efforts compared with more well known ailments.

The following information lists the affected gene(s), how often the disease occurs, how it is inherited, age of onset for symptoms, common symptoms, other known names, result of genetic mutation and prognosis for each leukodystrophy.  For more information please see our sources located at the bottom of this page.     

Adrenoleukodystrophy

Gene Affected- ABCD1

Disease Presence- 1:20,000 live births

Inheritance- x-linked recessive

Age of onset- ranges from 2 years to adulthood

Symptoms- emotional instability, hyperactivity, disruptive behavior; in adult forms it affects muscle stiffness, paraparesis and sexual dysfunction

Other names- x-linked ALD, ALD, x-ALD

Info- ALD is the most common peroxisomal disorder caused by a mutation of the ABCD1 gene.  There are a number of different ways ALD can be expressed, and there is no reliable way to tell which form a person will develop.  Left untreated, cerebral ALD is characterized by progressive demyelination leading to a vegetative state and death.

Adult-Onset Autosomal Dominant Leukodystrophy

Gene Affected- LMNB1

Disease Presence- unknown

Inheritance- autosomal recessive

Age of onset- adult (40-60 years old)

Symptoms- bladder retention, constipation, postural hypotension, erectile dysfunction, decreased sweating, cerebellar dysfunction (gait ataxia, loss of fine motor control, action tremors), spasticity, extremity weakness, cognitive impairment, personality changes

Other names- ADLD

Info- ADLD is caused by myelin disruption in the CNS, due to abnormalities in the LMNB1 gene.  ADLD tends to progress slowly and shortens life expectancy slightly.

Aicardi-Goutieres Syndrome

Gene Affected- TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHDI1, ADAR1, IFIH1

Disease Presence- over 120 cases reported

Inheritance- autosomal recessive and autosomal dominant

Age of onset- neonatal, early infancy

Symptoms- microcephaly, neonatal seizures, poor feeding, jitteriness, cerebral calcifications, significant intellectual and physical problems, persistent crying, intermittent fever, dystonia, exaggerated startle response, glaucoma

Other names- AGS

Info- AGS is a result of the mutation of a number of different genes.  Treatment is symptomatic with highly varying prognoses.

Alexander Disease

Gene Affected- GFAP

Disease Presence- fewer than 500 total reported cases

Inheritance- autosomal dominant, though most arise as spontaneous mutations

Age of onset- neonatal, infantile (0-2 years), juvenile (2-12 years), adult (over 12 years)

Symptoms- delays in physical/psychological/behavioral skills, macrocephaly, seizures, spasticity, hydrocephalus, idiopathic intracranial hypertension, dementia, gradual loss of bodily functions and ability to talk; in older onsent patients- bulbar symptoms and spasticity are common

Other names- fibrinoid leukodystrophy, AXD

Info- Alexander disease is caused by mutations in the GFAP gene, resulting in an excess of long chain fatty acids in the brain, which ruin the myelin.  Treatment is symptomatic and may include shunt placement to relieve cranial pressure.  There is no cure for Alexander disease and prognosis varies based on the age of onset.  Usually, the earlier the onset, the worse the prognosis.

CADASIL

Gene Affected- Notch 3 (chromosome 19)

Disease Presence- unknown

Inheritance- autosomal dominant

Age of onset- age 30 to 70

Symptoms- migraine headaches, transient ischemic attacks, strokes, mood disorders, subcortical dementia, pseudobulbar palsy, urinary incontinence

Other names- Cerebral Autosomal Dominant Arteropathy with Subcortical Infarts and Leukoencephalopathy

Info- CADASIL is a common inherited stroke disorder caused by mutations in the Notch 3 gene.  The disease is characterized by the progressive degeneration of smooth muscle cells in blood vessels.  Treatment and prognosis are unknown.

Canavan Disease

Gene Affected- ASPA

Disease Presence- unknown

Inheritance- autosomal recessive

Age of onset- neonatal, infancy and childhood

Symptoms- mild form includes developmental delay, problems with speech or achievement at school, urine NAA is slightly elevated; severe form includes hypotonia, developmental delay and other neurological impairments, very high NAA concentraion in urine, blood and cerebrospinal fluid

Other names- ACY2 deficiency, aminoacylase 2 deficiency, aspartoacylase deficiency, spongy degeneration of the brain, CD

Info- CD is caused by lack of or low levels of the aspartoacylase enzyme activity, resulting from mutations in the ASPA gene.  An onset of symptoms during neonatal or infancy align with the severe form of CD and average survival is 10 years, sometimes longer.  Symptoms that begin in childhood align with the mild form of CD and prognosis is good with a typically normal life expectancy.

CARASIL

Gene Affected- HTRA1

Disease Presence- unknown

Inheritance- autosomal recessive

Age of onset- adolescent and adult

Symptoms- diffuse alopecia, gait disturbance, lower and mid back pain, disk herniations, nodular thickening, severe spondylitis deformans with osteoporosis, lumbago with no radiological anormalities, lacunar stroke, stepwise deterioration in brain function, psuedobulbar palsy, hyperreflexia, vestibular symptoms, opthalmoplegia, forgetfulness, emotional incontinence, personality changes, disorientation in time, apallic syndrome, abulia, akinetic mutism

Other names- cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, Maeda syndrome

Info- CARASIL is a cerebral small vessel disease caused by a mutation in the HTRA1 gene.  The mutation leads to reduced or no amount of the gene which leads to increased signaling by the (TGF)-beta family, and the symptoms listed above.  There is currently no cure and treatment is symptomatic.  The prognosis is poor with the average duration of illness lasting 10 years.

Childhood Ataxia with Diffuse CNS Hypomyelination

Gene Affected- multiple EIF2B genes

Disease Presence- 148 total cases reported

Inheritance- autosomal recessive

Age of onset- childhood

Symptoms- extra-neurological affections, cognitive and behavioral dysfunction

Other names- CACH, vanishing white matter disease, myelinosis centralis diffusa

Info- CACH is caused by a mutation in the five EIF2B genes.  These genes are involved in protein synthesis and regulation.  Corticosteroids may be helpful in acute episodes.  Prognosis may correlate with age of onset, with the earliest onset being the most severe.

CTX

Gene Affected- CYP27A1

Disease Presence- more than 300 total reported cases; estimated at 1:50,000 live births in Caucasians

Inheritance- autosomal recessive

Age of onset- neonatal and infancy

Symptoms- chronic diarrhea from infancy, cataracts, cholestasis, liver dysfunction, intellectual impairment; later into adulthood patients may acquire dementia, psychiatric disturbances, seizures, neuropathy

Other names- cerebrotendineous xanthomatosis, cerebrotendinous xanthomatosis, cerebral cholesterosis, Van Bogaert-Scherer-Epstein syndrome

Info- CTX is a form of xanthomatosis caused by a mutation of the CYP27A1 gene.  It is associated with the deposition of cholestanol in the brain and other tissues, and higher levels of cholesterol in plasma.  Early diagnosis and treatment are crucial to prevent progressive accumulation of cholestanol and cholesterol. Treated patients may have a normal lifespan. In untreated patients, life expectancy is 50 to 60 years. Some early deaths in infancy have also been reported.

Fabry Disease

Gene Affected- GLA

Disease Presence- 1:80,000 live births

Inheritance- x-linked recessive

Age of onset- childhood

Symptoms- proteinuria, kidney failure, cardiomyopathy, transient ischemic attacks, stroke, burning or tingling paresthesia, burning pain, anhidrosis, hypohidrosis, angiokeratoma, corneal changes, tinnitus, chronic fatigue, cardiac and cerebrovascular abnormalities, dyspnea, nephropathy

Other names- alpha-galactosidase A deficiency, Anderson-Fabry disease, Angiokeratoma corporis diffusum, diffuse angiokeratoma, FD

Info- Fabry disease is a progressive, multi systemic lysosomal storage disease.  Enzyme enhancements with pharmacological chaperones and enzyme replacement therapy using in vitro engineered alpha-galactosidase A are under investigation.  Current treatment may include pain management, anti arrhythmic agents, pacemakers or implantable cardioverter defibrillator, dialysis and kidney transplant.  With time, the progression of the disease may cause organ failure.

Fucosidosis

Gene Affected- FUCA1

Disease Presence- 1:2,000,000 (fewer than 100 total cases reported)

Inheritance- autosomal recessive

Age of onset- type 1 is 0-18 months; type 2 is around 18 months; type 3 is approximately 1-2 years

Symptoms- progressive neurological deterioration, skin abnormalities, growth retardation, skeletal disease, coarsening of facial features, recurrent sinopulmonary infections, seizures, visceromegaly, angiokeratoma and dysostosis

Other names- n/a

Info- Fucosidosis is a rare lysosomal storage disorder where mutations in the FUCA1 gene drastically reduce or prohibit the alpha-L-fucosidase enzyme.  There are three types of the disease, with type 1 being the earliest age of onset and most severe.  Currently, treatment is symptomatic.  A bone marrow transplant may spur the production of normal amounts of fucosidase, however, more research is needed to prove the effectiveness of this treatment.  Prognosis ranges from less than six years with type 1, to 30-40 for other types.

GM1 Gangliosidosis

Gene Affected- GLB1

Disease Presence- 1:100,000 - 200,000 live births

Inheritance- autosomal recessive

Age of onset- type 1 is 0-6 months; type 2 is 7-36 months; type 3 is 3-30 years

Symptoms- delayed motor and cognitive development, generalized dystonia, facial coarsening, hypertrophic gums, cherry-red macula, visceromegaly, dysostosis, psychomotor delay

Other names- beta-galactosidase-1 deficiency, GLB1 deficiency, Landing disease

Info- GM1 gangliosidosis is a lysosomal storage disorder.  The mutation of gene GLB1 leads to toxic accumulation of gangliosides in body tissues and especially in the central nervous system.  There are three types of the disease based on the age of onset, with the most severe being type 1.  Currently there is no cure and treatment is symptomatic, but substrate reduction therapy is a potential approach for clinical trials in late-onset forms.

Krabbe Disease

Gene Affected- GALC (and rarely in infant form- PSAP)

Disease Presence- 1:100,000 - 250,000 live births

Inheritance- autosomal recessive

Age of onset- infantile (2-6 months); late infantile/juvenile (1-8 years); adult (8+ years)

Symptoms- infantile form symptoms include irritability, stiffness, poor head control, feeding difficulties, intermittent thumb clasp, episodes of increased temperature, developmental delay, hypertonic episodes with opisthotonus, myoclonic seizures, developmental regression, vision deficits, hypotonia, blindness, deafness; adult symptoms include weakness, gait disturbances, burning paresthesias, hemiplegia, vision loss, peripheral neuropathy, and potential cognitive regression

Other names- GALC deficiency, galactocerebrosidase deficiency, galactosylceramidase deficiency, globoid cell leukodystrophy

Info- Globoid cell leukodystrophy (Krabbe) is a lysosomal disorder that is caused by mutations in the GALC gene and affects the white matter of the central and peripheral nervous systems.  Current treatment is typically stem cell transplantation in pre-symptomatic infantile patients and mildly affected late-onset patients, and has been shown to slow disease progression.  Other treatment options are currently under research.  Prognosis is poor in infantile form (under 3 years).  The disease is normally fatal within 2-7 years of symptom onset in juvenile form.  Adult onset patient survival is much greater.

L-2-Hydroxyglutaric Aciduria

Gene Affected- L2HGDH

Disease Presence- fewer than 1:1,000,000

Inheritance- autosomal recessive

Age of onset- childhood

Symptoms- motor retardation, epilepsy, mental deterioration, speech difficulties, loss of independent walking, macrocephaly, hypotonia, spasticity, extrapyramidal symptoms, behavioral disorders, brain tumors

Other names- L-2-HGA; L-2-hydroxyglutaric acidemia

Info- L-2-hydroxyglutaric aciduria is the result of the mutation of the L2HGDH gene.  There is currently no cure and treatment is symptomatic.  Prognosis is poor but most patients reach adulthood.

Megalencephalic Leukoencephalopathy with Subcortical Cysts

Gene Affected- MCL1 (type 1), HEPACAM (type 2A and 2B), and 5% have unidentified mutations

Disease Presence- unknown

Inheritance- autosomal recessive or autosomal dominate

Age of onset- 0-12 months

Symptoms- megalencephaly, subcortical cysts, uncontrolled muscle tensing, involuntary writhing of limbs, difficulty swallowing, impaired speech, recurrent seizures, mild to moderate intellectual disability

Other names- MLC, megalencephalic leukodystrophy, megalencephaly-cystic leukodystrophy syndrome, vacuolating megalencephalic leukoencephalopathy with subcortical cysts, Van der Knaap syndrome

Info- There are three types of MLC that arise from either a mutation in the MCL1, HEPACAM or unidentified gene mutation.  Patients with MLC have enlarged myelin sheaths that contain fluid filled pockets  After time, the swelling goes down and the myelin sheath begins to deteriorate.  Treatment and prognosis for MLC is unknown.

Metachromatic Leukodystrophy

Gene Affected- ARSA (most), PSAP (few)

Disease Presence- 1:40,000

Inheritance- autosomal recessive

Age of onset- late infantile, juvenile, adult

Symptoms- abnormally high muscle tone, abnormal muscle movements, behavior problems, decreased mental function, decreased muscle tone, difficulty walking, feeding difficulties, frequent falls, inability to perform normal tasks, incontinence, irritability, loss of muscle control, nerve function problems, personality changes, poor school performance, seizures, speech difficulties, swallowing difficulties

Other names- MLD, arylsulfatase A deficiency

Info- MLD is caused by a lack of the arylsulfatase A enzyme.  Without this enzyme, an accumulation of sulfatides occur in a number of body tissues, ultimately leading to the destruction of myelin.  Prognosis varies based on the onset of symptoms, ranging in a disease course of usually three to 20+ years.

Multiple Sulfatase Deficiency

Gene Affected- SMUF1

Disease Presence- fewer than 1:1,000,000 individuals (prevalence)

Inheritance- autosomal recessive

Age of onset- neonatal and infancy

Symptoms- mildly coarsened facial features, deafness, ichthyosis, enlarged liver and spleen, severe mental retardation, hypotonia, hydrocephalus

Other names- Austin disease, mucosulfatidosis

Info- Multiple sulfatase deficiency is a lysosomal storage disease caused by a deficiency in multiple sufatase enzymes, or in formylglycine-generating enzyme, which activates sulfatases.

Pelizaeus Merzbacher Disease

Gene Affected- PLP1

Disease Presence- 1:400,000 invididuals

Inheritance- x-linked recessive or x-linked dominant

Age of onset- all ages, but classic onset is within 0-2 months of birth

Symptoms- hypotonia, nystagmus, respiratory distress, stridor, motor and cognitive delay, spastic quadriparesis, ataxia, spastic paraplegia, peripheral neuropathy

Other names- diffuse familial brain sclerosis, PMD, Pelizaeus-Merzbacher brain sclerosis, sudanophilic leukodystrophy

Info- PMD is a disorder caused by mutations or dosage alterations in the PLP1 gene.  These mutations cause CNS hypomyelination.  Treatment may include gastrostomy, anti epileptic medications, physical therapy, antispasticity drugs, or corrective surgery for pulmonary compromise in the case of severe scoliosis.  MPD is progressive, and prognosis varies on the disease form.  In moderate forms, life expectancy is quite long with slow disease progression.  In severe forms, death normally occurs within 20 years.

Pol III-Related Leukodystrophy

Gene Affected- POLR3A or POLR3B

Disease Presence- unknown

Inheritance- autosomal recessive

Age of onset- infancy, childhood and adolescent

Symptoms- hypomyelination, cerebellar atrophy, hypoplasia of the corpus callosum, intellectual disability (mild to severe), ataxia, delayed development of motor skills, unstable gait, tremor of arms and hands, abnormal teeth development, excessive salivation, dysphagia, speech impairment, abnormal eye movement, nearsightedness, cataracts, deterioration of the optic nerves, seizures, delayed signs of puberty

Other names- 4H, 4H syndrome, ADDH, dentoleukoencephalopathy, HCAHC, HLD7, HLD8, leukodystrophy with oligodontia, hypomyelination/hypodontia/hypogonadotropic/hypogonadism, LO, odontoleukodystrophy, Pol III disorder, TACH, tremor-ataxia with central hypomyelination

Info- Pol III leukodystrophy is caused by the mutation of either the POLR3A or POLR3B gene.  These genes facilitate the creation of RNA polymerase III, which aids synthesis of several forms of RNA, including ribosomal RNA and transfer RNA (tRNA).  These RNA molecules assemble protein building blocks into working proteins, and are essential to normal cell function.

Refsum Disease

Gene Affected- PHYH (over 90% of cases), PEX7 (fewer than 10% of cases)

Disease Presence- roughly 60 total cases reported

Inheritance- autosomal recessive

Age of onset- infancy, childhood, adolescent or adulthood

Symptoms- anosmia, early-onset retinitis pigmentosa, neuropathy, cerebellar ataxia, deafness, ichthyosis, skeletal abnormalities, cardiac arrhythmia, near blindness, sensory neuropathy, muscular atrophy, weakness, peripheral sensory disturbances, autism-spectrum disorder, ADHD, short metacarpals and metatarsals at birth

Other names- adult refsum disease, classic refsum disease, HMSN 4, hereditary motor and sensory neuropathy type 4, heredopathia atactica polyneuritiformis, phytanic-CoA hydroxylase deficiency

Info- Refsum disease is a clinically variable, multi systemic metabolic disease.  It is caused by mutations in either the PHYH or PEX7 gene, which are involved in lipid metabolism and protein transport.  Specific diet and supportive treatments are available to help manage symptoms.  Cardiac monitoring is required, as the main cause of death is arrhythmia and heart failure.  Prognosis in cases without treatment is generally poor.

Salla Disease

Gene Affected- SLC17A5

Disease Presence- fewer than 1:1,000,000 individuals (prevalence)

Inheritance- autosomal recessive

Age of onset- neonatal and infancy

Symptoms- nystagmus, hypotonia, reduced muscle tone and strength, cognitive impairment

Other names- sialic acid storage disease, Finnish type sialuria

Info- Salla disease is a lysosomal storage disease caused by a mutation in the SLC17A5 gene.

Sjogren-Larssen Syndrome

Gene Affected- ALDH3A2

Disease Presence- 1:250,000 in Sweden (unknown outside of Sweden)

Inheritance- autosomal recessive

Age of onset- early childhood

Symptoms- dry/scaly skin, red skin, itchiness, intellectual disability, speech difficulties, delayed speech, seizures, delayed motor skills, muscle stiffness, nearsightedness, sensitivity to light

Other names- FALDH deficiency, ichthyosis oligophrenia syndrome, SLS, congenital icthyosis mental retardation spasticity syndrome

Info- Sjogren Larssen Syndrome is caused by a mutation in the ALDH3A2 gene.  These mutations affect the normal process of fatty acid oxidation, which results in fat buildup in cells that can't be broken down.  The excess fat accumulations cause the symptoms listed above.  It is not clear what the consequences of excess fat accumulation is in the brain, but it is likely that it disrupts the formation of myelin.  These symptoms are apparent by early childhood and usually do not worsen with age.

Zellweger Syndrome

Gene Affected- one of the 13 PEX genes

Disease Presence- 1:50,000 live births in North America, 1:500,000 in Japan

Inheritance- autosomal recessive

Age of onset- neonatal

Symptoms- dysmorphic craniofacial features, profound hypotonia, seizures, macro and microcephaly, high arched palate, micrognathia, redundant neck skin folds, skeletal abnormalities, subcortical renal cysts, multiple eye findings, visual changes and loss, sensorineural hearing loss, psychomotor delay

Other names- ZS, cerebrohepatorenal syndrome

Info- Zellweger syndrome is the most severe variant of the peroxisome biogenesis disorders.  Mutations in the effected PEX gene lead to abnormal peroxisome biogenesis.  There is currently no cure for ZS.  Regardless of intervention, infants usually die within the first year of life.

References:

Below are the list of references for much of the above information.

www.orpha.net

https://www.nlm.nih.gov/

https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy

http://medical-dictionary.thefreedictionary.com/mucosulfatidosis

https://en.wikipedia.org/wiki/Online_Mendelian_Inheritance_in_Man

http://ghr.nlm.nih.gov/condition=fucosidosis

http://www.ismrd.org/glycoprotein_diseases/fucosidosis

http://children.webmd.com/fucosidosis

http://rarediseases.about.com/od/rarediseasesf/a/fucosidosis.htm

http://www.omim.org/entry/300100?search=x-ald&highlight=xald

 

http://www.ncbi.nlm.nih.gov/books/NBK1172/

 

http://www.ninds.nih.gov/disorders/alexander_disease

http://ulf.org/alexander-disease

 

Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. 

James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. 

Burk, R; Valle, D; Thomas, GH; Miller, C; Moser, A; Moser, H; Rosenbaum, KN (1984). "Early manifestations of multiple sulfatase deficiency†". The Journal of Pediatrics. 104 (4): 574–8. 

Farooqui AA, Horrocks LA (1984). "Biochemical aspects of globoid and metachromatic leukodystrophies". Neurochem Pathol. 2 (3): 189–218. 

Cosma MP, Pepe S, Annunziata I (May 2003). "The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases". Cell. 113 (4): 445–56. 

Annunziata I, Bouchè V, Lombardi A (September 2007). "Multiple sulfatase deficiency is due to hypomorphic mutations of the SUMF1 gene". Human Mutation. 28 (9): 298. 

Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. 

Schmidt, B; Selmer, T; Ingendoh, A; Von, Figura K (July 1995). "A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency". Cell. 82 (2): 271–8.

Aula N, A. P.; Aula, P. (August 2006). "Prenatal diagnosis of free sialic acid storage disorders (SASD)". Prenatal Diagnosis. 26 (8): 655–658. 

Autio-Harmainen H, Oldfors A, Sourander P, Renlund M, Dammert K, Simila S (1988). "Neuropathology of Salla disease". Acta Neuropathol. 75 (5): 481–490. 

Pilo de la Fuente B, Ruiz I, Lopez de Munain A, Jimenez-Escrig A (May 2008). "Cerebrotendinous xanthomatosis: Neuropathological findings". J. Neurol. 255 (6): 839–42. 

James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 535. .

L. van Bogaert, H. J. Scherer, E. Epstein. Une forme cérébrale de la cholestérinose généralisée (type particulier de lipidose à cholestérine). Paris, Masson, 1937.

Moser, Hugo W.; Smith, Kirby D.; Watkins, Paul A.; Powers, James; Moser, Ann (2001). "131. X-Linked Adrenoleukodystrophy". In Scriver, C.W.; Beaudet, A.L.; Sly, W.S.; Valle, D.; Childs, B.; Kinzler, K.W.; Vogelstein, B. Metabolic and Molecular Bases of Inherited Disease. 2 (8th ed.). New York: McGraw Hill. 

Berger, J.; Gärtner, J. (2006). "X-linked adrenoleukodystrophy: Clinical, biochemical and pathogenetic aspects". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1763 (12): 1721–1732. 

Steinberg, S. J.; Moser, A. B.; Raymond, G. V.; Pagon, R. A.; Bird, T. D.; Dolan, C. R.; Stephens, K.; Adam, M. P. (1993). "X-Linked Adrenoleukodystrophy". Gene Reviews. 

Hung KL, Wang JS, Keng WT, Chen HJ, Liang JS, Ngu LH, Lu JF (2013). "Mutational analyses on X-linked adrenoleukodystrophy reveal a novel cryptic splicing and three missense mutations in the ABCD1 gene". Pediatric Neurology. 49: 185–190. 

Aicardi J, Goutieres F (1984). "A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis". Ann Neurol. 15: 49–54.

Tolmie JL; Shillito P; Hughes-Benzie R; Stephenson JB. (1995). "The Aicardi-Goutieres syndrome (familial, early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis)". J Med Genet. 32: 881–884.

Aicardi, J; Goutieres, F (2000). "Systemic lupus erythematosus or Aicardi-Goutieres syndrome?". Neuropediatrics. 31: 113. 

Dale RC; Tang SP; Heckmatt JZ; Tatnall FM (2000). "Familial systemic lupus erythematosus and congenital infection-like syndrome". Neuropediatrics. 31: 155–158. 

Crow, YJ; Livingston, JH (2008). "Aicardi-Goutieres syndrome: an important Mendelian mimic of congenital infection". Dev Med Child Neurol. 50 (6): 410–416. 

Crow, YJ; et al. (2006). "Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus.". Nat Genet. 38 (8): 917–20. 

Crow, YJ; et al. (2006). "Mutations in the genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection". Nat Genet. 38 (8): 910–6. 

Rice, GI; et al. (2009). "Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response". Nat Genet. 41 (7): 829–32. 

Rice, GI; et al. (2012). "Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type 1 interferon signature". Nat Genet. 44 (11): 1243–8. 

Rice, GI; et al. (2014). "Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type 1 interferon signaling.". Nat Genet. 46: 503–509. 

Rice, GI; et al. (2007). "Clinical and molecular phenotype of Aicardi-Goutières syndrome". Am J Hum Genet. 81: 713–25. 

Crow, YJ; et al. (2004). "Congenital glaucoma and brain stem atrophy as features of Aicardi-Goutieres syndrome". Am J Med Genet. 129A: 303–7. 

Li R, Messing A, Goldman JE, Brenner M (2002). "GFAP mutations in Alexander disease". Int. J. Dev. Neurosci. 20 (3-5): 259–68. 

Quinlan RA, Brenner M, Goldman JE, Messing A (June 2007). "GFAP and its role in Alexander disease". Exp. Cell Res. 313 (10): 2077–87.

Messing A, Brenner M, Feany MB, Nedergaard M, Goldman JE (April 2012). "Alexander disease". J. Neurosci. 32 (15): 5017–23. 

Farina L, Pareyson D, Minati L, et al. (June 2008). "Can MR imaging diagnose adult-onset Alexander disease?". AJNR Am J Neuroradiol. 29 (6): 1190–6. 

Singh N, Bixby C, Etienne D, Tubbs RS, Loukas M (December 2012). "Alexander's disease: reassessment of a neonatal form". Childs Nerv Syst. 28 (12): 2029–31. 

Joutel A, Corpechot C, Ducros A, et al. (October 1996). "Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia". Nature. 383 (6602): 707–10. 

Chabriat H, Vahedi K, Iba-Zizen MT, et al. (October 1995). "Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy". Lancet. 346 (8980): 934–9. 

James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 545.

"CADASIL presenting as schizophreniform organic psychosis". General Hospital Psychiatry. 

Joutel A, Andreux F, Gaulis S, et al. (March 2000). "The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients". J. Clin. Invest. 105 (5): 597–605.