Adrenoleukodystrophy; ALD

What is Adrenoleukodystrophy; ALD?

Adrenoleukodystrophy; ALD is a rare disease. It is also known as Addison Disease And Cerebral Sclerosis Addison-Schilder's disease ALD Bronze Schilder Disease Melanodermic Leukodystrophy Siemerling-creutzfeldt Disease.

Also called Addison-Schilder's disease in the older literature, this X-linked disorder is variable in its mode of presentation. In the childhood form of the condition neurological signs usually have an onset between the ages of 5 and 10 years, when school performance tends to deteriorate and behaviour problems occur. Examination at this early stage might be normal but pyramidal tract signs develop early, followed by extra-pyramidal and cerebellar involvement. Symptoms of adrenal insufficiency (vomiting, diarrhoea, hypotension and hyperpigmentation) might be gross or subtle. The clasical picture in the later stages of the illness is that of a severe spastic quadriparesis. The CT scan appearance which shows low attenuation over the posterior cortex may suggest the diagnosis. Over half of all cases have the childhood form of the disorder, 25% have a later-onset presentation with adrenomyeloneuropathy, and 10% just have Addison's disease. The incidence of the disease appears to be between 1-2 per 100,000 livebirths (Bezman and Moser 1998; Kirk et al., 1998 and Ruiz et al., 1998). Very rarely the condition occurs as a spinocerebellar variant (Li et al., 2010).
Very long chain fatty acids (C26) (VLCFA) are increased. Long chain fatty acid levels are significantly reduced if the children are given high doses of erucic (C22) and oleic acids in a 4:1 mixture of glyceroltrioleate and glyceroltrierucate (Lorenzo's oil). This regime may cause giant platelets, which may not be recognised by automatic particle counters, with the result that thrombocytopenia is reported (Stockler et al., 1993). It is still not certain whether dietary treatment is effective (Moser, 1993). Korenke et al., (1995) provided evidence suggesting that therapy might help prevent neurological symptoms if started presymptomatically. However, van Geel et al., (1999) and Moser (1999) showed that treatment with Lorenzo's oil neither improved neurological or endocrine function nor arrested progression of the disease. In a study of 22 patients where two had asymptomatic ALD, four the "Addison only" variant, 13 adrenomyeloneuropathy, and three symptomatic female carriers. Bone marrow transplantation has also been tried (Aubourg et al., 1990; Malm et al.,1997). Baumann et al., (2003) studied the results of haematopoietic stem cell transplantation in 12 patients. This seemed to result in no deterioration in symptoms in six patients up to 5.5 years of treatment.
Carrier detection in the absence of a mutation or where linkage analysis is impossible, can be difficult and using VLCFA in plasma gives a 5-15% false negative rate (Moser et al., 1983). Using a combination of VLCFA and lignoceric acid oxidation in fibroblasts, detection is significantly improved (Inoue et al., 1996). DNA carrier detection is better. In a Spanish study (Coll et al., 2005) DNA analysis detected 80 heterozygous women, and 78 of these had abnormal biochemical levels.
Heterozygous females are occasionally affected. Dumic et al., (1992) reported two middle-aged sisters with adrenal insufficiency, hypothyroidism in one and Graves disease in the other, sparse hair and neurological symptoms.
Prenatal diagnosis can be carried out using cultured amniotic or CVS cells based on VLCFA levels (Moser and Moser 1999), however Carey et al., (1994) provide a caution, as they report a case where VLCFAs were normal in subculture 1 of a CVS but dramatically increased in subculture 3. Gray et al., (1995) also report a case of false-negative prenatal diagnosis looking at VLCFAs in cultured chorionic villus cells from an affected male fetus.
Mosser et al., (1993) demonstrated a deletion of a PMP70-like gene (ABCD1) (Peroxisomal Membrane Protein 70K) in 6 out of 85 independent cases. PMP70 is involved in peroxisomal biogenesis and the putative adrenoleukodystrophy protein (ALDP) appears to have a similar function (Mosser et al., 1994). Both proteins are members of the ATP-binding cassette transporter family. The number of detectable deletions or mutations has risen and in a study by Krasemann et al., (1996) 19 different mutations were found in the 20 families studied. There were eleven missense mutations, 2 nonsense mutations, 5 deletions and 1 insertion. Wichers et al., (1999) investigated the mutation spectrum in cases with adrenomyeloneuropathy but found no correlation between type of mutation and age of onset. However, Guimaraes et al., (2001) presented evidence suggesting that some late-onset patients have splice-site mutations. Kemp et al., (2001) review phenotype-genotype correlation in the condition. Corzo et al., (2002) reported three boys with neonatal onset of profound hypotonia, failure to thrive and colestatic liver disease. VLCFA levels were elevated. A deletion involving the ABCD1 gene and the neighbouring gene, DXS1357E was demonstrated. Onset in X-linked adrenoleukodystrophy is not usually until about 7 years of age.

Read More

* This information is courtesy of the L M D.

If you find a mistake or would like to contribute additional information, please email us at: [email protected]

What gene changes cause Adrenoleukodystrophy; ALD?

The syndrome is inherited in the following inheritance pattern/s:

X-Linked Recessive - Syndromes inherited in an X-linked recessive pattern generally only affect males. Males only have one X chromosome, and so one copy of a gene mutation on it causes the syndrome. Females, with two X chromosomes, only one of which will be mutated, are not likely to be affected.


In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation that occurs during the reproductive process.

OMIM Number - 300100 (please check the OMIM page for updated information)

The syndrome can be caused by mutations in the following gene/s location/s:
PEX13 - 2p15
PEX26 - 22q11.21
HMOX1 - 22q12.3
ABCD1 - Xq28
SOD2 - 6q25.3
IFNG - 12q15

What are the main symptoms of Adrenoleukodystrophy; ALD?

The typical symptoms of the syndrome are:
Hearing impairment, Incoordination, Impotence, Hypogonadism, Hyperpigmentation of the skin, Visual loss, Psychosis, Seizure, Polyneuropathy, Paraparesis, Elevated circulating long chain fatty acid concentration, Dementia, Truncal ataxia, Limb ataxia, Neurodegeneration, Loss of speech, Slurred speech, Spastic paraplegia, X-linked recessive inheritance, Urinary bladder sphincter dysfunction, Progressive, Abnormality of the skeletal system, Blindness, Attention deficit hyperactivity disorder, Bowel incontinence, Urinary incontinence, Primary adrenal insufficiency, Bulbar palsy, Abnormality of the cerebral white matter

How does someone get tested for Adrenoleukodystrophy; ALD?

The initial testing for Adrenoleukodystrophy; ALD can begin with facial genetic analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the type of genetic testing needed. A consultation with a genetic counselor and then a geneticist will follow.

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.

Get Faster and More Accurate Genetic Diagnosis!

More than 250,000 patients successfully analyzed!
Don't wait years for a diagnosis. Act now and save valuable time.

Start Here!

"Our road to a rare disease diagnosis was a 5-year journey that I can only describe as trying to take a road trip with no map. We didn’t know our starting point. We didn’t know our destination. Now we have hope."

Image

Paula and Bobby
Parents of Lillie

What is FDNA Telehealth?

FDNA Telehealth is a leading digital health company that provides faster access to accurate genetic analysis.

With a hospital technology recommended by leading geneticists, our unique platform connects patients with genetic experts to answer their most pressing questions and clarify any concerns they may have about their symptoms.

Benefits of FDNA Telehealth

FDNA icon

Credibility

Our platform is currently used by over 70% of geneticists and has been used to diagnose over 250,000 patients worldwide.

FDNA icon

Accessibility

FDNA Telehealth provides facial analysis and screening in minutes, followed by fast access to genetic counselors and geneticists.

FDNA icon

Ease of Use

Our seamless process begins with an initial online diagnosis by a genetic counselor and follows by consultations with geneticists and genetic testing.

FDNA icon

Accuracy & Precision

Advanced artificial intelligence (AI) capabilities and technology with a 90% accuracy rate for a more accurate genetic analysis.

FDNA icon

Value for
Money

Faster access to genetic counselors, geneticists, genetic testing, and a diagnosis. As fast as within 24 hours if required. Save time and money.

FDNA icon

Privacy & Security

We guarantee the utmost protection of all images and patient information. Your data is always safe, secure, and encrypted.

FDNA Telehealth can bring you closer to a diagnosis.
Schedule an online genetic counseling meeting within 72 hours!