Diagnosis often can be made through clinical examination and urine tests (excess mucopolysaccharides are excreted in the urine). Enzyme assays (testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the mucopolysaccharidoses. Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counseling can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.

Diagnosis often can be made through clinical examination and urine tests (excess mucopolysaccharides are excreted in the urine). Enzyme assays (testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the mucopolysaccharidoses. Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counseling can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.

The visible signs and symptoms of MPS II in younger people are usually the first clues leading to a diagnosis. In general, the time of diagnosis usually occurs about 2 to 4 years of age. Doctors may use laboratory tests to provide additional evidence that an MPS disorder is present, before making a definitive diagnosis, by measuring the iduronate-2-sulfatase (I2S) enzyme activity. The most commonly used laboratory screening test for an MPS disorder is a urine test for GAGs. The urine test for GAGs can occasionally be normal, yet the child still may have an MPS disorder. A definitive diagnosis of Hunter syndrome is made by measuring I2S activity in serum, white blood cells, or fibroblasts from skin biopsy. In some people with Hunter syndrome, analysis of the" I2S" gene can determine clinical severity. Prenatal diagnosis is routinely available by measuring I2S enzymatic activity in amniotic fluid or in chorionic villus tissue.

A large British study from 2008 found a median estimated life expectancy of 11.6 years.

Seven distinct clinical types and numerous subtypes of the mucopolysaccharidoses have been identified. Although each mucopolysaccharidosis (MPS) differs clinically, most patients generally experience a period of normal development followed by a decline in physical and/or mental function. (Note: MPS-V and MPS-VIII are no longer in use as designations for any disease.)

Clinical examination and MRI are often the first steps in a MLD diagnosis. MRI can be indicative of MLD, but is not adequate as a confirming test.

An ARSA-A enzyme level blood test with a confirming urinary sulfatide test is the best biochemical test for MLD. The confirming urinary sulfatide is important to distinguish between MLD and pseudo-MLD blood results.

Genomic sequencing may also confirm MLD, however, there are likely more mutations than the over 200 already known to cause MLD that are not yet ascribed to MLD that cause MLD so in those cases a biochemical test is still warranted.

"For further information, see the MLD Testing page at MLD Foundation."

The majority of patients is initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.

MPS-III A, B, C and D are considered to be clinically indistinguishable, although mutations in different genes are responsible for each disease. The following discussion is therefore applicable to all four conditions.

The disease manifests in young children. Affected infants are apparently normal, although some mild facial dysmorphism may be noticeable. The stiff joints, hirsuteness and coarse hair typical of other mucopolysaccharidoses are usually not present until late in the disease. After an initial symptom-free interval, patients usually present with a slowing of development and/or behavioral problems, followed by progressive intellectual decline resulting in severe dementia and progressive motor disease. Acquisition of speech is often slow and incomplete. The disease progresses to increasing behavioural disturbance including temper tantrums, hyperactivity, destructiveness, aggressive behaviour, pica and sleep disturbance. As affected children have normal muscle strength and mobility, the behavioural disturbances are very difficult to manage. The disordered sleep in particular presents a significant problem to care providers. In the final phase of the illness, children become increasingly immobile and unresponsive, often require wheelchairs, and develop swallowing difficulties and seizures. The life-span of an affected child does not usually extend beyond late teens to early twenties.

Although the clinical features of the disease are mainly neurological, patients may also develop diarrhea, carious teeth, and an enlarged liver and spleen. There is a broad range of clinical severity. The disease may very rarely present later in life as a psychotic episode.

Of all the MPS diseases, MPS III produces the mildest physical abnormalities. It is important, however, that simple and treatable conditions such as ear infections and toothaches not be overlooked because of behavior problems that make examination difficult. Children with MPS III often have an increased tolerance of pain. Bumps and bruises or ear infections that would be painful for other children often go unnoticed in children with MPS III. Parents may need to search for a doctor with the patience and interest in treating a child with a long-term illness. Some children with MPS III may have a blood-clotting problem during and after surgery.

The diagnosis may be confirmed by assay of enzyme levels in tissue samples and gene sequencing. Prenatal diagnosis is possible.

Diagnosis of the lipid storage disorders can be achieved through the use of several tests. These tests include clinical examination, biopsy, genetic testing, molecular analysis of cells or tissues, and enzyme assays. Certain forms of this disease can also be diagnosed through urine testing which will detect the stored material. Prenatal testing is also available to determine if the fetus will have the disease or is a carrier.

Treatment remains largely supportive. The behavioral disturbances of MPS-III respond poorly to medication. If an early diagnosis is made, bone marrow replacement may be beneficial. Although the missing enzyme can be manufactured and given intravenously, it cannot penetrate the blood–brain barrier and therefore cannot treat the neurological manifestations of the disease.

Along with many other lysosomal storage diseases, MPS-III exists as a model of a monogenetic disease involving the central nervous system.

Several promising therapies are in development. Gene therapy in particular is under Phase I/II clinical trial in France since October 2011 under the leadership of Paris-based biotechnology company Lysogene. Other potential therapies include chemical modification of deficient enzymes to allow them to penetrate the blood–brain barrier, stabilisation of abnormal but active enzyme to prevent its degradation, and implantation of stem cells strongly expressing the missing enzyme. For any future treatment to be successful, it must be administered as early as possible. Currently MPS-III is mainly diagnosed clinically, by which stage it is probably too late for any treatment to be very effective. Neonatal screening programs would provide the earliest possible diagnosis.

The flavonoid genistein decreases the pathological accumulation of glycosaminoglycans in Sanfilippo syndrome. "In vitro", animal studies and clinical experiments suggest that the symptoms of the disease may be alleviated by an adequate dose of genistein. Despite its reported beneficial properties, genistein also has toxic side effects.

Several support and research groups have been established to speed the development of new treatments for Sanfilippo syndrome.

Because of the very specific nature of the illness, treatment has proven very difficult. The treatment for this disorder is specifically determined for each patient, because all cases are different.

The degeneration of white matter, which shows the degeneration of myelin, can be seen in a basic MRI and used to diagnose leukodystrophies of all types. T-1 and T-2 weighted FLAIR images are the most useful. FLAIR stands for fluid-attenuated inversion recovery. Electrophysiological and other kinds of laboratory testing can also be done. In particular, nerve conduction velocity is looked at to distinguish between leukodystrophy and other demyelinating diseases, as well as to distinguish between individual leukodystrophies. For example, individuals with X-ALD have normal conduction velocities, while those with Krabbe disease or metachromatic leukodystrophy have abnormalities in their conduction velocities. Next generation multigene sequencing panels for undifferentiated leukodystrophy can now be offered for rapid molecular diagnosis after appropriate genetic counselling.

The symptoms of LSD vary, depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with LSDhave enlarged livers (hepatomegaly) and enlarged spleens (splenomegaly), pulmonary and cardiac problems, and bones that grow abnormally.

MSD has an autosomal recessive inheritance pattern.

The inheritance probabilities "per birth" are as follows:

- If both parents are carriers:

- 25% (1 in 4) children will have the disorder

- 50% (2 in 4) children will be carriers (but unaffected)

- 25% (1 in 4) children will be free of MSD - unaffected child that is not a carrier

- If one parent is affected and one is free of MSD:

- 0% (0) children will have the disorder - only one parent is affected, other parent always gives normal gene

- 100% (4 in 4) children will be carriers (but unaffected)

- If one parent is a carrier and the other is free of MSD:

- 50% (2 in 4) children will be carriers (but unaffected)

- 50% (2 in 4) children will be free of MSD - unaffected child that is not a carrier

MLD has an autosomal recessive inheritance pattern. The inheritance probabilities "per birth" are as follows:

- If both parents are carriers:

- 25% (1 in 4) children will have the disease

- 50% (2 in 4) children will be carriers, but unaffected

- 25% (1 in 4) children will be free of MLD – unaffected child that is not a carrier

- If one parent is affected and one is free of MLD:

- 0% (0) children will have the disorder – only one parent is affected, other parent always gives normal gene

- 100% (4 in 4) children will be carriers (but unaffected)

- If one parent is a carrier and the other is free of MLD:

- 50% (2 in 4) children will be carriers (but unaffected)

- 50% (2 in 4) children will be free of MLD – unaffected child that is not a carrier

In addition to these frequencies there is a 'pseudo'-deficiency that affects 7–15% of the population. People with the pseudo deficiency do not have any MLD problems unless they also have affected status. With the current diagnostic tests, Pseudo-deficiency reports as low enzyme levels but sulfatide is processed normally so MLD symptoms do not exist. This phenomenon wreaks havoc with traditional approaches to Newborn Screening so new screening methods are being developed.

"For further information, see recessive gene and dominance relationship. Also, consult the MLD genetics page at MLD Foundation."

The treatment for Morquio syndrome consists of prenatal identification and of enzyme replacement therapy. On 12 February 2014, the US Food and Drug Administration approved the drug elosulfase alfa (Vimizim) for treating the disease.

The activity of arylsulfatase E can be measured with the substrate 4-methylumbelliferyl sulfate.

CDPX1 activity may be inhibited by warfarin because it is believed that ARSE has enzymatic activity in a vitamin K producing biochemical pathway. Vitamin K is also needed for controlling binding of calcium to bone and other tissues within the body.

Onset of adult GM1 is between ages 3 and 30.

Symptoms include muscle atrophy, neurological complications that are less severe and progress at a slower rate than in other forms of the disorder, corneal clouding in some patients, and dystonia (sustained muscle contractions that cause twisting and repetitive movements or abnormal postures). Angiokeratomas may develop on the lower part of the trunk of the body. Most patients have a normal size liver and spleen.

Prenatal diagnosis is possible by measurement of Acid Beta Galactosidase in cultured amniotic cells.

XLI can be suspected based on clinical findings, although symptoms can take varying amounts of time to become evident, from a few hours after birth, up to a year in milder cases. The diagnosis is usually made by a dermatologist, who also typically formulates the treatment plan (see below). STS enzyme deficiency is confirmed using a clinically available biochemical assay. Carrier detection can be performed in mothers of affected sons using this test (see Genetics, below). Molecular testing for DNA deletions or mutations is also offered, and can be particularly useful in the evaluation of individuals with associated medical conditions (see below). Prenatal diagnosis is possible using either biochemical or molecular tests. However, the use of prenatal diagnosis for genetic conditions that are considered to be generally benign raises serious ethical considerations and requires detailed genetic counseling.

There are no specific treatments for lipid storage disorders; however, there are some highly effective enzyme replacement therapies for people with type 1 Gaucher disease and some patients with type 3 Gaucher disease. There are other treatments such as the prescription of certain drugs like phenytoin and carbamazepine to treat pain for patients with Fabry disease. Furthermore, gene thereapies and bone marrow transplantation may prove to be effective for certain lipid storage disorders. Diet restrictions do not help prevent the buildup of lipids in the tissues.

Currently, no research has shown a higher prevalence of most leukodsytrophy types in any one place around the world. There is, however, a higher prevalence of the Canavan disease in the Jewish population for unknown reasons. 1 in 40 individuals of Ashkenazi Jewish descent are carriers of Canavan disease. This estimates to roughly 2.5%. Additionally, due to an autosomal recessive inheritance patterns, there is no significant difference found between affected males and affected females for most types of leukodystrophy including, but not limited to, metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease. The one exception to this is any type of leukodystrophy carried on a sex chromosome, such as X-linked adrenoleukodystrophy, which is carried on the X-chromosome. Because of the inheritance pattern of X-linked diseases, males are more often affected by this type of leukodystrophy, although female carriers are often symptomatic, though not as severely so as males. To date, there have been no found cases of a leukodystrophy carried on the Y chromosome.

This syndrome has two forms, A and B, referred to as Morquio A and Morquio B syndrome or MPA IVA and MPS IVB. The two forms are distinguished by the gene product involved; A involves a malfunction in the GALNS gene product (galactosamine-6 sulfatase), while B involves a malfunction of the GLB1 gene product (beta-galactosidase).

Multiple sulfatase deficiency (also known as "Austin disease", and "mucosulfatidosis") is a very rare autosomal recessive lysosomal storage disease caused by a deficiency in multiple sulfatase enzymes, or in formylglycine-generating enzyme, which activates sulfatases. It is similar to mucopolysaccharidosis.

Onset of late infantile GM1 is typically between ages 1 and 3 years.

Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.