The most characteristic biochemical indicator of SLOS is an increased concentration of 7DHC (reduced cholesterol levels are also typical, but appear in other disorders as well). Thus, prenatally, SLOS is diagnosed upon finding an elevated 7DHC:total sterol ratio in fetal tissues, or increased levels of 7DHC in amniotic fluid. The 7DHC:total sterol ratio can be measured at 11–12 weeks of gestation by chorionic villus sampling, and elevated 7DHC in amniotic fluid can be measured by 13 weeks. Furthermore, if parental mutations are known, DNA testing of amniotic fluid or chorionic villus samples may be performed.

Amniocentesis (process of sampling amniotic fluid) and chorionic villus sampling cannot be performed until approximately 3 months into the pregnancy. Given that SLOS is a very severe syndrome, parents may want to choose to terminate their pregnancy if their fetus is affected. Amniocentesis and chorionic villus sampling leave very little time to make this decision (abortions become more difficult as the pregnancy advances), and can also pose severe risks to the mother and baby. Thus, there is a very large desire for noninvasive midgestation diagnostic tests. Examining the concentrations of sterols in maternal urine is one potential way to identify SLOS prenatally. During pregnancy, the fetus is solely responsible for synthesizing the cholesterol needed to produce estriol. A fetus with SLOS cannot produce cholesterol, and may use 7DHC or 8DHC as precursors for estriol instead. This creates 7- or 8-dehydrosteroids (such as 7-dehydroestriol), which may show up in the maternal urine. These are novel metabolites due to the presence of a normally reduced double bond at carbon 7 (caused by the inactivity of DHCR7), and may be used as indicators of SLOS. Other cholesterol derivatives which possess a double bond at the 7th or 8th position and are present in maternal urine may also be indicators of SLOS. 7- and 8-dehydropregnanetriols have been shown to be present in the urine of mothers with an affected fetus but not with an unaffected fetus, and thus are used in diagnosis. These pregnadienes originated in the fetus and traveled through the placenta before reaching the mother. Their excretion indicates that neither the placenta nor the maternal organs have necessary enzymes needed to reduce the double bond of these novel metabolites.

If SLOS goes undetected until after birth, diagnosis may be based on the characteristic physical features as well as finding increased plasma levels of 7DHC.

There are many different ways of detecting 7DHC levels in blood plasma, one way is using the Liebermann–Burchard (LB) reagent. This is a simple colorimetric assay developed with the intention of use for large scale screening. When treated with the LB reagent, SLOS samples turn pink immediately and gradually become blue; normal blood samples are initially colorless and develop a faint blue color. Although this method has limitations and is not used to give a definitive diagnosis, it has appeal in that it is a much faster method than using cell cultures.

Another way of detecting 7DHC is through gas chromatography, a technique used to separate and analyze compounds. Selected ion

monitoring gas chromatography/mass-spectrometry (SIM-GC/MS) is a very sensitive version of gas chromatography, and permits detection of even mild cases of SLOS. Other methods include time-of-flight mass spectrometry, particle-beam LC/MS, electrospray tandem MS, and ultraviolet absorbance, all of which may be used on either blood samples, amniotic fluid, or chorionic villus. Measuring levels of bile acids in patients urine, or studying DCHR7 activity in tissue culture are also common postnatal diagnostic techniques.

Plasma and cerebrospinal fluid levels of pipecolic acid are frequently elevated in patients with PDE, though it is a non-specific biomarker. α-aminodipic semialdehyde is elevated in urine and plasma and is a more specific biomarker for PDE. Improvements in these biomarkers have been reported with the implementation of a lysine-restricted diet. Initial studies evaluating the safety and efficacy of lysine restriction evaluated developmental and cognitive outcomes by age-appropriate tests and parental observations.

Direct sequence analysis of genomic DNA from blood can be used to perform a mutation analysis for the TALDO1 gene responsible for the Transaldolase enzyme.

Autozygome analysis and biochemical evaluations of urinary sugars and polyols can be used to diagnose Transaldolase Deficiency. Two specific methods for measuring the urinary sugars and polyols are liquid chromatographytandem mass spectrometry and gas chromatography with flame ionization detection.

Patients with PDE do not respond to anticonvulsant medications, but seizures rapidly cease with therapeutic intravenous doses of Vitamin B6 and remission from seizures are often maintained on daily therapeutic doses of Vitamin B6. An optimal dose has not yet been established, but doses of 50–100 mg/day or 15–30 mg/kg/day have been proposed. Importantly, excessive doses of vitamin B6 can result in irreversible neurological damage, and therefore several guidelines recommend 500 mg per day as the maximal daily dose.

Despite remission of seizure activity with vitamin B6 supplementation, intellectual disability is frequently seen in patients with PDE. Because the affected enzyme antiquitin is involved in the cerebral lysine degradation pathway, lysine restriction as an additional treatment modality has recently been explored. Studies have been published which demonstrate potential for improved biomarkers, development, and behavior in patients treated with lysine restriction in addition to pyridoxine supplementation. In trial, lysine restriction of 70–100 mg/kg/day in children less than 1 year of age, 45–80 mg/kg/day in children between 1–7 years of age, and 20–45 mg/kg/day in children older than 7 years of age were prescribed. Despite the potential of additional benefit from lysine restriction, vitamin B6 supplementation remains the main-stay of treatment given lack of studies thus far demonstrating the safety and efficacy of lysine restriction for this purpose.

Recent research has been focused on studying large series of cases of 3-M syndrome to allow scientists to obtain more information behind the genes involved in the development of this disorder. Knowing more about the underlying mechanism can reveal new possibilities for treatment and prevention of genetic disorders like 3-M syndrome.

- One study looks at 33 cases of 3M syndrome, 23 of these cases were identified as CUL7 mutations: 12 being homozygotes and 11 being heterozygotes. This new research shows genetic heterogeneity in 3M syndrome, in contrast to the clinical homogeneity. Additional studies are still ongoing and will lead to the understanding of this new information.

- This study provides more insight on the three genes involved in 3M syndrome and how they interact with each other in normal development. It lead to the discovery that the CUL7, OBS1, and CCDC8 form a complex that functions to maintain microtubule and genomic integrity.

Treatment of 3-M syndrome is aimed at the specific symptoms presented in each individual. With the various symptoms of this disorder being properly managed and affected individuals having normal mental development, 3-M syndrome is not a life - threatening condition and individuals are able to lead a near normal life with normal life expectancy.

Treatment may involve the coordinated efforts of many healthcare professionals, such as pediatricians, orthopedists, dentists and/or other specialists depending on the symptoms.

- Possible management options for short stature are surgical bone lengthening or growth hormone therapy.

- Orthopedic techniques and surgery may be used to treat certain skeletal abnormalities.

- Plastic surgery may also be performed on individuals to help correct certain cranio-facial anomalies.

- Individuals with dental abnormalities may undergo corrective procedures such as braces or oral surgeries.

The caloric intake of children with SRS must be carefully controlled in order to provide the best opportunity for growth. If the child is unable to tolerate oral feeding, then enteral feeding may be used, such as the percutaneous endoscopic gastrostomy.

In children with limb-length differences or scoliosis, physiotherapy can alleviate the problems caused by these symptoms. In more severe cases, surgery to lengthen limbs may be required. To prevent aggravating posture difficulties children with leg length differences may require a raise in their shoe.

Growth hormone therapy is often prescribed as part of the treatment of SRS. The hormones are given by injection typically daily from the age of 2 years old through teenage years. It may be effective even when the patient does not have a growth hormone deficiency. Growth hormone therapy has been shown to increase the rate of growth in patients and consequently prompts 'catch up' growth. This may enable the child to begin their education at a normal height, improving their self-esteem and interaction with other children. The effect of growth hormone therapy on mature and final height is as yet uncertain. There are some theories suggesting that the therapy also assists with muscular development and managing hypoglycemia.

Lafora Disease is diagnosed by doing a series of tests by a neurologist, epileptologist (person who specializes in epilepsy), or geneticist. To confirm the diagnosis, an EEG, MRI, and genetic testing are needed to detect the activity of the brain and potential genetic relation to Lafora Disease. A biopsy may be necessary as well to detect and confirm the presence of Lafora bodies in the skin. Typically, if a patient comes to a doctor and has been having seizures, like patients with LD characteristically have, these are the common tests that would happen right away to figure out areas of the brain where the seizures are occurring. Whole genome or exome testing is necessary to have with anyone who suffers from epilepsy.

Raine syndrome (RNS), also called osteosclerotic bone dysplasia, is a rare autosomal recessive congenital disorder characterized by craniofacial anomalies including microcephaly, noticeably low set ears, osteosclerosis, a cleft palate, gum hyperplasia, a hypoplastic nose, and eye proptosis. It is considered to be a lethal disease, and usually leads to death within a few hours of birth. However, a recent report describes two studies in which children with Raine Syndrome have lived to 8 and 11 years old, so it is currently proposed that there is a milder expression that the phenotype can take (Simpson 2009).

It was first characterized in 1989 in a report that was published on an infant that had been born with an unknown syndrome, that later came to be called Raine Syndrome.

The current research describes Raine Syndrome as a neonatal osteosclerotic bone dysplasia, indicated by its osteosclerotic symptoms that are seen in those suffering from the disease. It has been found that a mutation in the gene FAM20C is the cause of the Raine Syndrome phenotype. This microdeletion mutation leads to an unusual chromosome 7 arrangement. The milder phenotypes of Raine Syndrome, such as those described in Simpson’s 2007 report, suggest that Raine Syndrome resulting from missense mutations may not be as lethal as the other described mutations (OMIM). This is supported by findings from Fradin et al. (2011), who reported on children with missense mutations to FAM20C and lived to ages 1 and 4 years, relatively much longer than the life spans of the previously reported children. Simpson et al.’s (2007) report states that to date, effected individuals have had chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion. They had abnormal chromosome 7 arrangements, with microdeletions of their D7S2477 and D7S1484 markers (Simpson 2007).

Raine Syndrome appears to be an autosomal recessive disease. There are reports of recurrence in children born of the same parents, and an increased occurrence in children of closely related, genetically similar parents. Individuals with Raine Syndrome were either homozygous or compound heterozygous for the mutation of FAM20C. Also observed have been nonsynonomous mutation and splice-site changes (Simpson et al. 2007).

FAM20C, located on chromosome 7p22.3, is an important molecule in bone development. Studies in mice have demonstrated its importance in the mineralization of bones in teeth in early development (OMIM, Simpson et al. 2007, Wang et al. 2010). FAM20C stands for “family with sequence similarity 20, member C.” It is also commonly referred to as DMP-4. It is a Golgi-enriched fraction casein kinase and an extracellular serine/threonine protein kinase. It is 107,743 bases long, with 10 exons and 584 amino acids (Weizmann Institute of Science).

Histopathology. The skin shows hyperkeratosis, hyper-granulosis, and acanthosis. Pathognomonic findings occur in the basal and suprabasal cells of the epidermis, which demonstrate variably sized vacuoles that contain lipid accumulations

Vestronidase alfa-vjbk (Mepsevii) is the only drug approved by U.S. Food and Drug Administration for the treatment of pediatric and adult patients.

Since phytanic acid is not produced in the human body, individuals with Refsum disease are commonly placed on a phytanic acid-restricted diet and avoid the consumption of fats from ruminant animals and certain fish, such as tuna, cod, and haddock. Grass feeding animals and their milk are also avoided. Recent research has shown that CYP4 isoform enzymes could help reduce the over-accumulation of phytanic acid "in vivo". Plasmapheresis is another medical intervention used to treat patients. This involves the filtering of blood to ensure there is no accumulation of phytanic acid.

Marshall–Smith syndrome is not to be confused with:

- Marshall syndrome (aka.Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome, see also: Periodic fever syndrome)

- Sotos (like) syndrome

- Weaver-Smith syndrome (WSS)

Respiratory complications are often cause of death in early infancy.

Relationships between the disease and perlecan deficiency have been studied.

Silver–Russell syndrome (SRS), also called Silver–Russell dwarfism or Russell–Silver syndrome (RSS) is a growth disorder occurring in approximately 1/50,000 to 1/100,000 births. In the United States it is usually referred to as Russell–Silver syndrome, and Silver–Russell syndrome elsewhere. It is one of 200 types of dwarfism and one of five types of primordial dwarfism and is one of the few forms that is considered treatable in some cases.

There is no statistical significance of the syndrome occurring preferentially in either males or females.

The most useful information for accurate diagnosis is the symptoms and weakness pattern. If the quadriceps are spared but the hamstrings and iliopsoas are severely affected in a person between ages of 20 - 40, it is very likely HIBM will be at the top of the differential diagnosis. The doctor may order any or all of the following tests to ascertain if a person has IBM2:

- Blood test for serum Creatine Kinase (CK or CPK);

- Nerve Conduction Study (NCS) / Electomyography (EMG);

- Muscle Biopsy;

- Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) Scan to determine true sparing of quadriceps;

- Blood Test or Buccal swab for genetic testing;

Schwartz–Jampel syndrome (SJS) is a rare genetic disease caused by a mutation in the HSPG2 gene, which makes the protein perlecan, and causing osteochondrodysplasia associated with myotonia.

Most people with Schwartz–Jampel syndrome have a nearly normal life expectancy.

The basic tests performed when an immunodeficiency is suspected should include a full blood count (including accurate lymphocyte and granulocyte counts) and immunoglobulin levels (the three most important types of antibodies: IgG, IgA and IgM).

Other tests are performed depending on the suspected disorder:

- Quantification of the different types of mononuclear cells in the blood (i.e. lymphocytes and monocytes): different groups of T lymphocytes (dependent on their cell surface markers, e.g. CD4+, CD8+, CD3+, TCRαβ and TCRγδ), groups of B lymphocytes (CD19, CD20, CD21 and Immunoglobulin), natural killer cells and monocytes (CD15+), as well as activation markers (HLA-DR, CD25, CD80 (B cells).

- Tests for T cell function: skin tests for delayed-type hypersensitivity, cell responses to mitogens and allogeneic cells, cytokine production by cells

- Tests for B cell function: antibodies to routine immunisations and commonly acquired infections, quantification of IgG subclasses

- Tests for phagocyte function: reduction of nitro blue tetrazolium chloride, assays of chemotaxis, bactericidal activity.

Due to the rarity of many primary immunodeficiencies, many of the above tests are highly specialised and tend to be performed in research laboratories.

Criteria for diagnosis were agreed in 1999. For instance, an antibody deficiency can be diagnosed in the presence of low immunoglobulins, recurrent infections and failure of the development of antibodies on exposure to antigens. The 1999 criteria also distinguish between "definitive", "probable" and "possible" in the diagnosis of primary immunodeficiency. "Definitive" diagnosis is made when it is likely that in 20 years, the patient has a >98% chance of the same diagnosis being made; this level of diagnosis is achievable with the detection of a genetic mutation or very specific circumstantial abnormalities. "Probable" diagnosis is made when no genetic diagnosis can be made, but the patient has all other characteristics of a particular disease; the chance of the same diagnosis being made 20 years later is estimated to be 85-97%. Finally, a "possible" diagnosis is made when the patient has only some of the characteristics of a disease are present, but not all.

The confirmatory diagnosis is made via brain biopsy, however, other tests can be used to help such as MRI, EEG, CT, as well as the physical exam and history

Because lack of sialic acid appears to be part of the pathology of IBM caused by GNE mutations, clinical trials with sialic acid supplements, and with a precursor of sialic acid, N-Acetylmannosamine, have been conducted, and as of 2016 further trials were planned.

Unfortunately there is no cure for Lafora Disease with treatment being limited to controlling seizures through anti-epileptic and anti-convulsant medications. The treatment is usually based on the individual's specific symptoms and the severity of those symptoms. Some examples of medications include valproate, levetiracetam, topiramate, benzodiazepines, or perampanel. Although the symptoms and seizures can be controlled for a long period by using anti-epileptic drugs, the symptoms will progress and patients lose their ability to perform daily activities leading to the survival rate of approximately 10 years after symptoms begin. Quality of life worsens as the years go on, with some patients requiring a feeding tube so that they can get the nutrition and medication they need in order to keep functioning, but not necessarily living.

Sly syndrome, also called mucopolysaccharidosis type VII (MPS 7), is an autosomal recessive lysosomal storage disease characterized by a deficiency of the enzyme β-glucuronidase, a lysosomal enzyme. Sly syndrome belongs to a group of disorders known as mucopolysaccharidoses, which are lysosomal storage diseases. In Sly syndrome, the deficiency in β-glucuronidase leads to the accumulation of certain complex carbohydrates (mucopolysaccharides) in many tissues and organs of the body.

It was named after its discoverer William S. Sly, an American biochemist who has spent nearly his entire academic career at Saint Louis University.