Metachromatic leukodystrophy
Synonyms and keywords: Arylsulfatase A deficiency

# Overview
Metachromatic leukodystrophy  is the most common form of a family of genetic diseases known as the leukodystrophies, diseases which affect the growth and/or development of myelin, the fatty covering which acts as an insulator around nerve fibres throughout the central and peripherial nervous systems .

# Classification
Based on the age of onset, Metachromatic Leukodystrophy is classified into three types.
Types:
- Late infantile onset (before 30 months)
- Juvenile onset ( 2.5 years to 16 years)
- Adult onset

# Pathophysiology
Metachromatic leukodystrophy is caused by deficiency of Arylsulfatase A (ASA), an autosomal recessive disorder.

# Causes
Disease name] may be caused by , , or .
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Common causes of  include , , and .
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The most common cause of  is . Less common causes of  include , , and .
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The cause of  has not been identified. To review risk factors for the development of , click here.

# Differentiating Metachromatic leukodystrophy from other Diseases
 must be differentiated from other diseases that cause , , and , such as , , and .
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 must be differentiated from , , and .

# Epidemiology and Demographics
The incidence/prevalence of  is approximately  per 100,000 individuals worldwide.
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In , the incidence/prevalence of  was estimated to be  cases per 100,000 individuals worldwide.
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In , the incidence of  is approximately  per 100,000 individuals with a case-fatality rate of %.
Patients of all age groups may develop .
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The incidence of  increases with age; the median age at diagnosis is  years.
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 commonly affects individuals younger than/older than  years of age.
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 is usually first diagnosed among .
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 commonly affects .
There is no racial predilection to .
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 usually affects individuals of the  race.  individuals are less likely to develop .
 affects men and women equally.
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 are more commonly affected by  than . The  to  ratio is approximately  to 1.
The majority of  cases are reported in .
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 is a common/rare disease that tends to affect  and .

# Risk Factors
There are no established risk factors for .
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The most potent risk factor in the development of  is . Other risk factors include , , and .
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Common risk factors in the development of  include , , , and .
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Common risk factors in the development of  may be occupational, environmental, genetic, and viral.

# Screening
There is insufficient evidence to recommend routine screening for .
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According to the , screening for  is not recommended.
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According to the , screening for  by  is recommended every  among patients with , , and .

# Natural History, Complications, and Prognosis
If left untreated, % of patients with  may progress to develop , , and .
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Common complications of  include , , and .
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Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with  is approximately %.

# Diagnosis

## Diagnostic Study of Choice
The diagnosis of  is made when at least  of the following  diagnostic criteria are met: , , , and .
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The diagnosis of  is based on the  criteria, which include , , and .
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The diagnosis of  is based on the  definition, which includes , , and .
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There are no established criteria for the diagnosis of .

## History and Symptoms
The majority of patients with  are asymptomatic.
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The hallmark of  is . A positive history of  and  is suggestive of . The most common symptoms of  include , , and . Common symptoms of  include , , and . Less common symptoms of  include , , and .

## Physical Examination
Patients with  usually appear . Physical examination of patients with  is usually remarkable for , , and .
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Common physical examination findings of  include , , and .
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The presence of  on physical examination is diagnostic of .
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The presence of  on physical examination is highly suggestive of .

## Laboratory Findings
An elevated/reduced concentration of serum/blood/urinary/CSF/other  is diagnostic of .
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Laboratory findings consistent with the diagnosis of  include , , and .
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 is usually normal among patients with .
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Some patients with  may have elevated/reduced concentration of , which is usually suggestive of .
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There are no diagnostic laboratory findings associated with .

## Electrocardiogram
There are no ECG findings associated with .
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An ECG may be helpful in the diagnosis of . Findings on an ECG suggestive of/diagnostic of  include , , and .

## X-ray
There are no x-ray findings associated with .
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An x-ray may be helpful in the diagnosis of . Findings on an x-ray suggestive of/diagnostic of  include , , and .
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There are no x-ray findings associated with . However, an x-ray may be helpful in the diagnosis of complications of , which include , , and .

## Echocardiography or Ultrasound
There are no echocardiography/ultrasound  findings associated with .
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Echocardiography/ultrasound  may be helpful in the diagnosis of . Findings on an echocardiography/ultrasound suggestive of/diagnostic of  include , , and .
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There are no echocardiography/ultrasound  findings associated with . However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of , which include , , and .

## CT scan
There are no CT scan findings associated with .
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 CT scan may be helpful in the diagnosis of . Findings on CT scan suggestive of/diagnostic of  include , , and .
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There are no CT scan findings associated with . However, a CT scan may be helpful in the diagnosis of complications of , which include , , and .

## MRI
There are no MRI findings associated with .
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 MRI may be helpful in the diagnosis of . Findings on MRI suggestive of/diagnostic of  include , , and .
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There are no MRI findings associated with . However, a MRI may be helpful in the diagnosis of complications of , which include , , and .

## Other Imaging Findings
There are no other imaging findings associated with .
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 may be helpful in the diagnosis of . Findings on an  suggestive of/diagnostic of  include , , and .

## Other Diagnostic Studies
There are no other diagnostic studies associated with .
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 may be helpful in the diagnosis of . Findings suggestive of/diagnostic of  include , , and .
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Other diagnostic studies for  include , which demonstrates , , and , and , which demonstrates , , and .

# Treatment

## Medical Therapy
There is no treatment for ; the mainstay of therapy is supportive care.
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Supportive therapy for  includes , , and .
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The majority of cases of  are self-limited and require only supportive care.
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 is a medical emergency and requires prompt treatment.
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The mainstay of treatment for  is .
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The optimal therapy for  depends on the stage at diagnosis.
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 is recommended among all patients who develop .
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Pharmacologic medical therapy is recommended among patients with , , and .
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Pharmacologic medical therapies for  include (either) , , and/or .
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Empiric therapy for  depends on  and .
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Patients with  are treated with , whereas patients with  are treated with .

## Surgery
Surgical intervention is not recommended for the management of .
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Surgery is not the first-line treatment option for patients with . Surgery is usually reserved for patients with either , , and 
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The mainstay of treatment for  is medical therapy. Surgery is usually reserved for patients with either , , and/or .
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The feasibility of surgery depends on the stage of  at diagnosis.
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Surgery is the mainstay of treatment for .

## Primary Prevention
There are no established measures for the primary prevention of .
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There are no available vaccines against .
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Effective measures for the primary prevention of  include , , and .
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 vaccine is recommended for  to prevent . Other primary prevention strategies include , , and .

## Secondary Prevention
There are no established measures for the secondary prevention of .
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Effective measures for the secondary prevention of  include , , and .

### Clinical Trials
Enzyme Replacement Therapy
- Phase II clinical trials are underway in Europe by a Danish company, Zymenex, using Metazym, (updated August 2007)
- Shire Human Genetics is proposing an enzyme replacement therapy