Menkes syndrome can be diagnosed by blood tests of the copper and ceruloplasmin levels, skin biopsy, and optical microscopic examination of the hair to view characteristic Menkes abnormalities. X-rays of the skull and skeleton are conducted to look for abnormalities in bone formation. Urine homovanillic acid/vanillylmandelic acid ratio has been proposed as a screening tool to support earlier detection. Since 70% of MNK cases are inherited, genetic testing of the mother can be performed to search for a mutation in the ATP7A gene.

Due to the wide range of genetic disorders that are presently known, diagnosis of a genetic disorder is widely varied and dependent of the disorder. Most genetic disorders are diagnosed at birth or during early childhood, however some, such as Huntington's disease, can escape detection until the patient is well into adulthood.

The basic aspects of a genetic disorder rests on the inheritance of genetic material. With an in depth family history, it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth, or contemplate termination. Prenatal diagnosis can detect the presence of characteristic abnormalities in fetal development through ultrasound, or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis.

Blood lactate and pyruvate levels usually are elevated as a result of increased anaerobic metabolism and a decreased ratio of ATP:ADP. CSF analysis shows an elevated protein level, usually >100 mg/dl, as well as an elevated lactate level.

A neuro-ophthalmologist is usually involved in the diagnosis and management of KSS. An individual should be suspected of having KSS based upon clinical exam findings. Suspicion for myopathies should be increased in patients whose ophthalmoplegia does not match a particular set of cranial nerve palsies (oculomotor nerve palsy, fourth nerve palsy, sixth nerve palsy). Initially, imaging studies are often performed to rule out more common pathologies. Diagnosis may be confirmed with muscle biopsy, and may be supplemented with PCR determination of mtDNA mutations.

Not all genetic disorders directly result in death, however there are no known cures for genetic disorders. Many genetic disorders affect stages of development such as Down syndrome. While others result in purely physical symptoms such as muscular dystrophy. Other disorders, such as Huntington's disease show no signs until adulthood. During the active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy. This includes physical therapy, pain management, and may include a selection of alternative medicine programs.

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."

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.

The severity of different forms of PCH varies, but many children inheriting the mutated gene responsible do not survive infancy or childhood; nevertheless, some individuals born with PCH have reached adulthood.

The diagnosis of short-chain acyl-coenzyme A dehydrogenase deficiency is based on the following:

- Newborn screening test

- Genetic testing

- Urine test

A detailed family history should be obtained from at least three generations. In particularly a history to determine if there has been any neonatal and childhood deaths: Also a way to determine if any one of the family members exhibit any of the features of the multi-system disease. Specifically if there has been a maternal inheritance, when the disease is transmitted to females only, or if there is a family member who experienced a multi system involvement such as: Brain condition that a family member has been record to have such asseizures, dystonia, ataxia, or stroke like episodes.The eyes with optic atrophy, the skeletal muscle where there has been a history of myalgia, weakness or ptosis. Also in the family history look for neuropathy and dysautonomia, or observe heart conditions such ascardiomyopathy. The patients history might also exhibit a problem in their kidney, such as proximal nephron dysfunction. An endocrine condition, for example diabetes and hypoparathyroidism. The patient might have also had gastrointestinal condition which could have been due to liver disease, episodes of nausea or vomiting. Multiple lipomas in the skin, sideroblastic anemia and pancytopenia in the metabolic system or short stature might all be examples of patients with possible symptoms of MERRF disease.

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.

The use of biochemical testing for the detection of carriers is technically demanding and not often used. Biochemical analyses that have been performed on hair bulbs from at risk women have had a small number of both false positive and false negative outcomes. If only a suspected carrier female is available for mutation testing, it may be appropriate to grow her lymphocytes in 6-thioguanine (a purine analogue), which allows only HGPRT-deficient cells to survive. A mutant frequency of 0.5–5.0 × 10 is found in carrier females, while a non-carrier female has a frequency of 1–20 × 10. This frequency is usually diagnostic by itself.

Molecular genetic testing is the most effective method of testing, as HPRT1 is the only gene known to be associated with LNS. Individuals who display the full Lesch–Nyhan phenotype all have mutations in the HPRT1 gene. Sequence analysis of mRNA is available clinically and can be utilized in order to detect HPRT1 mutations in males affected with Lesch–Nyhan syndrome. Techniques such as RT-PCR, multiplex genomic PCR, and sequence analysis (cDNA and genomic DNA), used for the diagnosis of genetic diseases, are performed on a research basis. If RT-PCR tests result in cDNA showing the absence of an entire exon or exons, then multiplex genomic PCR testing is performed. Multiplex genomic PCR testing amplifies the nine exons of the HPRT1 gene as eight PCR products. If the exon in question is deleted, the corresponding band will be missing from the multiplex PCR. However, if the exon is present, the exon is sequenced to identify the mutation, therefore causing exclusion of the exon from cDNA. If no cDNA is created by RT-PCR, then multiplex PCR is performed on the notion that most or all of the gene is obliterated.

The long-term prognosis of Costeff syndrome is unknown, though it appears to have no effect on life expectancy at least up to the fourth decade of life. However, as mentioned previously, movement problems can often be severe enough to confine individuals to a wheelchair at an early age, and both visual acuity and spasticity tend to worsen over time.

The differential diagnosis for short-chain acyl-coenzyme A dehydrogenase deficiency is: ethylmalonic encephalopathy, mitochondrial respiratory chain defects and "multiple" acyl-CoA dehydrogenase deficiency.

There is no cure for Menkes disease. Early treatment with injections of copper supplements (in the form of acetate salts) may be of some slight benefit. Among 12 newborns who were diagnosed with MNK, 92% were alive at age 4.6. Other treatment is symptomatic and supportive. Treatments to help relieve some of the symptoms includes, pain medication, anti-seizure medication, feeding tube when necessary, and physical and occupational therapy.

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.

While there is no cure for BGS, symptoms can be treated as they arise. Surgery shortly after birth can repair craniosynostosis, as well as defects in the hand to create a functional grasp. There are risks associated with untreated craniosynostosis, therefore surgery is often needed to separate and reshape the bones. Since patients with a RECQL4 mutation may be at an increased risk of developing cancer, surveillance is recommended.

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

The urate to creatinine (breakdown product of creatine phosphate in muscle) concentration ratio in urine is elevated. This is a good indicator of acid overproduction. For children under ten years of age with LNS, a urate to creatinine ratio above two is typically found. Twenty-four-hour urate excretion of more than 20 mg/kg is also typical but is not diagnostic. Hyperuricemia (serum uric acid concentration of >8 mg/dL) is often present but not reliable enough for diagnosis. Activity of the HGPRT enzyme in cells from any type of tissue (e.g., blood, cultured fibroblasts, or lymphoblasts) that is less than 1.5% of normal enzyme activity confirms the diagnosis of Lesch–Nyhan syndrome. Molecular genetic studies of the HPRT gene mutations may confirm diagnosis, and are particularly helpful for subsequent 'carrier testing' in at-risk females such as close family relatives on the female side.

There is currently no cure for Costeff syndrome. Treatment is supportive, and thus focuses on management of the symptoms. The resulting visual impairment, spasticity, and movement disorders are treated in the same way as similar cases occurring in the general population.

Pyruvate dehydrogenase deficiency can be diagnosed via the following methods:

- Blood test (Lactate and pyruvate levels)

- Urine analysis

- Magnetic resonance spectroscopy

- MRI

1. Blood. With Pearson Syndrome, the bone marrow fails to produce white blood cells called neutrophils. The syndrome also leads to anemia, low platelet count, and aplastic anemia It may be confused with transient erythroblastopenia of childhood.

2. Pancreas. Pearson Syndrome causes the exocrine pancreas to not function properly because of scarring and atrophy

Individuals with this condition have difficulty absorbing nutrients from their diet which leads to malabsorption. infants with this condition generally do not grow or gain weight.

Biotinidase deficiency can be found by genetic testing. This is often done at birth as part of newborn screening in several states throughout the United States. Results are found through testing a small amount of blood gathered through a heel prick of the infant. As not all states require that this test be done, it is often skipped in those where such testing is not required. Biotinidase deficiency can also be found by sequencing the "BTD" gene, particularly in those with a family history or known familial gene mutation.

The differential diagnosis of pyruvate dehydrogenase deficiency can consist of either D-Lactic acidosis or abnormalities associated with gluconeogenesis.

Diagnosis of mitochondrial trifunctional protein deficiency is often confirmed using tandem mass spectrometry. It should be noted that genetic counseling is available for this condition. Additionally the following exams are available:

- CBC

- Urine test