Diagnosis of canine phosphofructokinase deficiency is similar to the blood tests used in diagnosis of humans. Blood tests measuring the total erythrocyte PFK activity are used for definitive diagnosis in most cases. DNA testing for presence of the condition is also available.

Treatment mostly takes the form of supportive care. Owners are advised to keep their dogs out of stressful or exciting situations, avoid high temperature environments and strenuous exercise. It is also important for the owner to be alert for any signs of a hemolytic episode. Dogs carrying the mutated form of the gene should be removed from the breeding population, in order to reduce incidence of the condition.

A diagnosis can be made through a muscle biopsy that shows excess glycogen accumulation. Glycogen deposits in the muscle are a result of the interruption of normal glucose breakdown that regulates the breakdown of glycogen. Blood tests are conducted to measure the activity of phosphofructokinase, which would be lower in a patient with this condition. Patients also commonly display elevated levels of creatine kinase.

Treatment usually entails that the patient refrain from strenuous exercise to prevent muscle pain and cramping. Avoiding carbohydrates is also recommended.

A ketogenic diet also improved the symptoms of an infant with PFK deficiency. The logic behind this treatment is that the low-carb high fat diet forces the body to use fatty acids as a primary energy source instead of glucose. This bypasses the enzymatic defect in glycolysis, lessening the impact of the mutated PFKM enzymes. This has not been widely studied enough to prove if it is a viable treatment, but testing is continuing to explore this option.

Genetic testing to determine whether or not a person is a carrier of the mutated gene is also available.

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

The diagnosis of glycogen storage disease IX consists of the following:

- Complete blood count

- Urinalysis

- Histological study of the liver (via biopsy)

- Genetic testing

- Physical exam

There are two types of this inherited condition, "glycogen storage disease IXa1" and "glycogen storage disease IXa2" that affect the liver of an individual. Mutations in PHKA2 have been seen in individuals with glycogen storage disease IXa2.

In terms of the diagnosis for glycogen storage disease type III, the following tests/exams are carried out to determine if the individual has the condition:

- Biopsy (muscle or liver)

- CBC

- Ultrasound

- DNA mutation analysis (helps ascertain GSD III subtype)

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

- Newborn screening test

- Genetic testing

- Urine test

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

The differential diagnosis of glycogen storage disease type III includes GSD I, GSD IX and GSD VI. This however does not mean other glycogen storage diseases should not be distinguished as well.

Management for mitochondrial trifunctional protein deficiency entails the following:

- Avoiding factors that might precipitate condition

- Glucose

- Low fat/high carbohydrate nutrition

There is some laboratory tests that may aid in diagnosis of GSD-V. A muscle biopsy will note the absence of myophosphorylase in muscle fibers. In some cases, acid-Schiff stained glycogen can be seen with microscopy.

Genetic sequencing of the PYGM gene (which codes for the muscle isoform of glycogen phosphorylase) may be done to determine the presence of gene mutations, determining if McArdle's is present. This type of testing is considerably less invasive than a muscle biopsy.

The physician can also perform an ischemic forearm exercise test as described above. Some findings suggest a nonischemic test could be performed with similar results. The nonischemic version of this test would involve not cutting off the blood flow to the exercising arm. Findings consistent with McArdle’s disease would include a failure of lactate in venous blood and exaggerated ammonia levels. These findings would indicate a severe muscle glycolytic block. Ammonia arises from the impaired buffering of ADP, which leads to an increase in AMP concentration resulting in an increase in AMP deamination.

Physicians may also check resting levels of creatine kinase, which are moderately increased in 90% of patients. In some, the level is increased by multitudes - a person without GSD-V will have a CK between 60 and 400IU/L, while a person with the syndrome may have a level of 5,000 IU/L at rest, and may increase to 35,000 IU/L or more with muscle exertion. This can help distinguish McArdle's syndrome from carnitine palmitoyltransferase II deficiency (CPT-II), a lipid-based metabolic disorder which prevents fatty acids from being transported into mitochondria for use as an energy source. Also, serum electrolytes and endocrine studies (such as thyroid function, parathyroid function and growth hormone levels) will also be completed. Urine studies are required only if rhabdomyolysis is suspected. Urine volume, urine sediment and myoglobin levels would be ascertained. If rhabdomyolysis is suspected, serum myoglobin, creatine kinase, lactate dehydrogenase, electrolytes and renal function will be checked.

Liver biopsy for microscopic analysis and enzyme assay is required for definitive diagnosis. Diagnosis may include linkage analysis in families with affected members and sequencing of the entire coding region of the GSY2 gene for mutations.

Treatment is depended on the type of glycogen storage disease. E.g. GSD I is typically treated with frequent small meals of carbohydrates and cornstarch to prevent low blood sugar, while other treatments may include allopurinol and human granulocyte colony stimulating factor.

The initial workup of abetalipoproteinemia typically consists of stool sampling, a blood smear, and a fasting lipid panel though these tests are not confirmatory. As the disease is rare, though a genetics test is necessary for diagnosis, it is generally not done initially.

Acanthocytes are seen on blood smear. Since there is no or little assimilation of chylomicrons, their levels in plasma remains low.

The inability to absorb fat in the ileum will result in steatorrhea, or fat in the stool. As a result, this can be clinically diagnosed when foul-smelling stool is encountered. Low levels of plasma chylomicron are also characteristic.

There is an absence of apolipoprotein B. On intestinal biopsy, vacuoles containing lipids are seen in enterocytes. This disorder may also result in fat accumulation in the liver (hepatic steatosis). Because the epithelial cells of the bowel lack the ability to place fats into chylomicrons, lipids accumulate at the surface of the cell, crowding the functions that are necessary for proper absorption.

Amniocentesis or chorionic villus sampling can be used to screen for the disease before birth. After birth, urine tests, along with blood tests and skin biopsies can be used to diagnose Schindler disease. Genetic testing is also always an option, since different forms of Schindler disease have been mapped to the same gene on chromosome 22; though different changes (mutations) of this gene are responsible for the infantile- and adult-onset forms of the disease.

Serum glucose levels are measured to document the degree of hypoglycemia. Serum electrolytes calculate the anion gap to determine presence of metabolic acidosis; typically, patients with glycogen-storage disease type 0 (GSD-0) have an anion gap in the reference range and no acidosis. See the Anion Gap calculator.

Serum lipids (including triglyceride and total cholesterol) may be measured. In patients with glycogen-storage disease type 0, hyperlipidemia is absent or mild and proportional to the degree of fasting.

Urine (first voided specimen with dipstick test for ketones and reducing substances) may be analyzed. In patients with glycogen-storage disease type 0, urine ketones findings are positive, and urine-reducing substance findings are negative. However, urine-reducing substance findings are positive (fructosuria) in those with fructose 1-phosphate aldolase deficiency (fructose intolerance).

Serum lactate is in reference ranges in fasting patients with glycogen-storage disease type 0.

Liver function studies provide evidence of mild hepatocellular damage in patients with mild elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.Plasma amino-acid analysis shows plasma alanine levels as in reference ranges during a fast.

The diagnosis of CTD is usually suspected based on the clinical presentation of mental retardation, abnormalities in cognitive and expressive speech, and developmental delay. Furthermore, a family history of X-linked intellectual disability, developmental coordination disorder, and seizures is strongly suggestive. Initial screening of CTD involves obtaining a urine sample and measuring the ratio of creatine to creatinine. If the ratio of creatine to creatinine is greater than 1.5, then the presence of CTD is highly likely. This is because a large ratio indicates a high amount of creatine in the urine. This, in turn, indicates inadequate transport of creatine into the brain and muscle. However, the urine screening test often fails in diagnosing heterozygous females. Studies have demonstrated that as a group heterozygous females have significantly decreased cerebral creatine concentration, but that individual heterozygous females often have normal creatine concentrations found in their urine. Therefore, urine screening tests are unreliable as a standard test for diagnosing CTD.

A more reliable and sophisticated manner of testing for cerebral creatine concentrations is through "in vivo" proton magnetic resonance spectroscopy (1H MRS). "In vivo" 1H MRS uses proton signals to determine the concentration of specific metabolites. This method of testing is more reliable because it provides a fairly accurate measurement of the amount of creatine inside the brain. Similar to urine testing, a drawback of using 1H MRS as a test for CTD is that the results of the test could be attributed to any of the cerebral creatine deficiencies. The most accurate and reliable method of testing for CTD is through DNA sequence analysis of the SLC6A8 gene. DNA analysis of SLC6A8 allows the identification of the location and type of mutation causing the cerebral creatine deficiency. Furthermore, DNA analysis of SLC6A8 is able to prove that a cerebral creatine deficiency is due to CTD and not GAMT or AGAT deficiency.

The usual initial investigations include chest X ray, electrocardiogram and echocardiography. Typical findings are those of an enlarged heart with non specific conduction defects. Biochemical investigations include serum creatine kinase (typically increased 10 fold) with lesser elevations of the serum aldolase, aspartate transaminase, alanine transaminase and lactic dehydrogenase. Diagnosis is made by estimating the acid alpha glucosidase activity in either skin biopsy (fibroblasts), muscle biopsy (muscle cells) or in white blood cells. The choice of sample depends on the facilities available at the diagnostic laboratory.

In the late onset form, the findings on investigation are similar to those of the infantile form with the caveat that the creatinine kinases may be normal in some cases. The diagnosis is by estimation of the enzyme activity in a suitable sample.

On May 17, 2013 the Secretary's Discretionary Advisory Committee on Heritable Diseases in Newborns and Children (DACHDNC) approved a recommendation to the Secretary of Health and Human Services to add Pompe to the Recommended Uniform Screening Panel (RUSP). The HHS secretary must first approve the recommendation before the disease is formally added to the panel.

Infants with Schindler disease tend to die within 4 years of birth, therefore, treatment for this form of the disease is mostly palliative. However, Type II Schindler disease, with its late onset of symptoms, is not characterized by neurological degeneration. There is no known cure for Schindler disease, but bone marrow transplants have been trialed, as they have been successful in curing other glycoprotein disorders.

Supervised exercise programs have been shown in small studies to improve exercise capacity by several measures.

Oral sucrose treatment (for example a sports drink with 75 grams of sucrose in 660 ml.) taken 30 minutes prior to exercise has been shown to help improve exercise tolerance including a lower heart rate and lower perceived level of exertion compared with placebo.

A genetic test is available for Type 1 PSSM. This test requires a blood or hair sample, and is less-invasive than muscle biopsy. However, it may be less useful for breeds that are more commonly affected by Type 2 PSSM, such as light horse breeds. Often a muscle biopsy is recommended for horses displaying clinical signs of PSSM but who have negative results for GYS1 mutation.

A muscle biopsy may be taken from the semimembranosis or semitendinosis (hamstring) muscles. The biopsy is stained for glycogen, and the intensity of stain uptake in the muscle, as well as the presence of any inclusions, helps to determine the diagnosis of PSSM. This test is the only method for diagnosing Type 2 PSSM. Horses with Type 1 PSSM will usually have between 1.5-2 times the normal levels of glycogen in their skeletal muscle. While abnormalities indicating muscle damage can be seen on histologic sections of muscle as young as 1 month of age, abnormal polysaccharide accumulation may take up to 3 years to develop.

Overall, according to a study in British Columbia, approximately 2.3 children per 100,000 births (1 in 43,000) have some form of glycogen storage disease. In the United States, they are estimated to occur in 1 per 20,000–25,000 births. Dutch incidence rate is estimated to be 1 per 40,000 births.

The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level. When combined with an increased concentration of carnitine in urine, the suspicion of SPCD can often be confirmed by either molecular testing or functional studies assessing the uptake of carnitine in cultured fibroblasts.

Identification of patients presymptomatically via newborn screening has allowed early intervention and treatment. Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life. Individuals who are identified and treated at birth have very good outcomes, including the prevention of cardiomyopathy. Mothers who are identified after a positive newborn screen but are otherwise asymptomatic are typically offered carnitine supplementation as well. The long-term outcomes for asymptomatic adults with SPCD is not known, but the discovery of mothers with undiagnosed cardiomyopathy and SPCD has raised the possibility that identification and treatment may prevent adult onset manifestations.

There are exceptions, but levels of alpha-glucosidase determines the type of GSD II an individual may have. More alpha glucosidase present in the individuals muscles means symptoms occur later in life and progress more slowly. GSD II is broadly divided into two onset forms based on the age symptoms occur.

Infantile-onset form is usually diagnosed at 4–8 months; muscles appear normal but are limp and weak preventing them from lifting their head or rolling over. As the disease progresses heart muscles thicken and progressively fail. Without treatment death usually occurs due to heart failure and respiratory weakness.

Late or later onset form occurs later than one to two years and progresses more slowly than Infantile-onset form. One of the first symptoms is a progressive decrease in muscle strength starting with the legs and moving to smaller muscles in the trunk and arms, such as the diaphragm and other muscles required for breathing. Respiratory failure is the most common cause of death. Enlargement of the heart muscles and rhythm disturbances are not significant features but do occur in some cases.

Treatments for Glycerol Kinase Deficiency are targeted to treat the symptoms because there are no permanent treatments for this disease. The main way to treat these symptoms is by using corticosteroids, glucose infusion, or mineralocorticoids. Corticosteroids are steroid hormones that are naturally produced in the adrenal glands. These hormones regulate stress responses, carbohydrate metabolism, blood electrolyte levels, as well as other uses. The mineralocorticoids, such as aldosterone control many electrolyte levels and allow the kidneys to retain sodium. Glucose infusion is coupled with insulin infusion to monitor blood glucose levels and keep them stable.

Due to the multitude of varying symptoms of this disease, there is no specific treatment that will cure this disease altogether. The symptoms can be treated with many different treatments and combinations of medicines to try to find the correct combination to offset the specific symptoms. Everyone with Glycerol Kinase Deficiency has varying degrees of symptoms and thereby requires different medicines to be used in combination to treat the symptoms; however, this disease is not curable and the symptoms can only be managed, not treated fully.