The goal for treatment of GSD type 0 is to avoid hypoglycemia. This is accomplished by avoiding fasting by eating every 3-4 hours during the day. At night, uncooked corn starch can be given because it is a complex glucose polymer. This will be acted on slowly by pancreatic amylase and glucose will be absorbed over a 6 hour period.

The only treatment for classic galactosemia is eliminating lactose and galactose from the diet. Even with an early diagnosis and a restricted diet, however, some individuals with galactosemia experience long-term complications such as speech difficulties, learning disabilities, neurological impairment (e.g. tremors, etc.), and ovarian failure. Symptoms have not been associated with Duarte galactosemia, and many individuals with Duarte galactosemia do not need to restrict their diet at all. However, research corroborates a previously overlooked theory that Duarte galactosemia may lead to language developmental issues in children with no clinical symptoms. Infants with classic galactosemia cannot be breast-fed due to lactose in human breast milk and are usually fed a soy-based formula.

Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition. Lactose intolerant individuals have an acquired or inherited shortage of the enzyme lactase, and experience abdominal pains after ingesting dairy products, but no long-term effects. In contrast, a galactosemic individual who consumes galactose can cause permanent damage to their bodies.

Long term complication of galactosemia includes:

- Speech deficits

- Ataxia

- Dysmetria

- Diminished bone density

- Premature ovarian failure

- Cataract

There is no broadly accepted standard of care for infants with DG. Some healthcare providers recommend partial to complete dietary restriction of milk and other high galactose foods for infants or young children with DG; others do not. Because children with DG develop increased tolerance for dietary galactose as they grow, few healthcare providers recommend dietary restriction of lactose or galactose beyond early childhood.

The rationale for NOT restricting dietary galactose exposure of infants and/or young children with DG: Healthcare providers who do not recommend dietary restriction of galactose for infants with DG generally consider DG to be of no clinical significance—meaning most infants and children with DG seem to be doing clinically well. Further, these providers may be opposed to interrupting or reducing breastfeeding when there is no clear evidence it is contraindicated. These providers may argue that the recognized health benefits of breastfeeding outweigh the potential risks of as yet unknown negative effects of continued milk exposure for these infants. For infants with DG who continue to drink milk, some doctors would recommend that blood galactose-1-phosphate (Gal-1P) or urinary galactitol be rechecked by age 12 months to ensure that these metabolite levels are normalizing.

The rationale FOR restricting dietary galactose exposure of infants and/or young children with DG: Healthcare providers who recommend partial or complete dietary restriction of galactose for infants and/or young children with DG generally cite concern about the unknown long-term consequences of abnormally elevated galactose metabolites in a young child's blood and tissues. Infants with DG who continue to drink milk accumulate the same set of abnormal galactose metabolites seen in babies with classic galactosemia – e.g. galactose, Gal-1P, galactonate, and galactitol – but to a lesser extent. While it remains unclear whether any of these metabolites contribute to the long-term developmental complications experienced by so many older children with classic galactosemia, the possibility that they might cause problems serves to motivate some healthcare providers to recommend dietary galactose restriction for infants with DG. Switching an infant with DG from milk or milk formula (high galactose) to soy formula (low galactose) rapidly normalizes their galactose metabolites. This approach is considered potentially preventative rather than responsive to acute symptoms.

If dietary galactose restriction of any kind is followed, healthcare providers may recommend that the child have a galactose challenge to re-evaluate galactose tolerance before the restrictive diet is discontinued. Most infants or young children with DG who are followed by a metabolic specialist are discharged from follow up after a successful galactose challenge.Options for those choosing to restrict dietary galactose in infancy and/or early childhood: Dietary restriction practices for Duarte galactosemia vary widely. In the US, some healthcare providers recommend full dietary restriction of milk and all dairy products for the first 12 months of life, followed by a galactose challenge. Some providers recommend the galactose challenge before 12 months, others after. Some providers who recommend dietary intervention suggest a "compromise approach" if the parent wishes to breastfeed, such that the parent alternates feedings of breast milk and low galactose formula. Finally, some parents choose to continue some form of dietary galactose restriction for their child with DG beyond early childhood.

What is a galactose challenge? The goal of a galactose challenge is to learn whether a child is able to metabolize dietary galactose sufficiently to prevent the abnormal accumulation of galactose metabolites, generally measured as Gal-1P in the blood. For infants with DG who showed elevated galactose metabolites at diagnosis, this test can be used to see if their ability to process galactose has improved enough to discontinue dietary galactose restriction.

To test galactose metabolism, a baseline Gal-1P level is measured while the child is on a galactose-restricted diet. If the level is within the normal range (e.g. <1.0 mg/dL), the parent/guardian is advised to "challenge" the child with dietary galactose—meaning feed the child a diet that includes normal levels of milk for 2–4 weeks. Immediately after that time, another blood sample is collected and analyzed for Gal-1P level. If this second result is still in the normal range, the child is said to have "passed" their galactose challenge, and dietary galactose restrictions are typically relaxed or discontinued. If the second test shows elevated Gal-1P levels, the parent/guardian may be advised to resume galactose restriction for the child, and the "challenge" may be repeated after a few months.

Treatment of HFI depends on the stage of the disease, and the severity of the symptoms. Stable patients without acute intoxication events are treated by careful dietary planning that avoids fructose and its metabolic precursors. Fructose is replaced in the diet by glucose, maltose or other sugars. Management of patients with HFI often involves dietitians who have a thorough knowledge of what foods are acceptable.

To treat people with a deficiency of this enzyme, they must avoid needing gluconeogenesis to make glucose. This can be accomplished by not fasting for long periods, and eating high-carbohydrate food. They should avoid fructose containing foods (as well as sucrose which breaks down to fructose).

As with all single-gene metabolic disorders, there is always hope for genetic therapy, inserting a healthy copy of the gene into existing liver cells.

There is no cure for GALT deficiency, in the most severely affected patients, treatment involves a galactose free diet for life. Early identification and implementation of a modified diet greatly improves the outcome for patients. The extent of residual GALT enzyme activity determines the degree of dietary restriction. Patients with higher levels of residual enzyme activity can typically tolerate higher levels of galactose in their diets. As patients get older, dietary restriction is often relaxed. With the increased identification of patients and their improving outcomes, the management of patients with galactosemia in adulthood is still being understood.

After diagnosis, patients are often supplemented with calcium and vitamin D3. Long-term manifestations of the disease including ovarian failure in females, ataxia. and growth delays are not fully understood. Routine monitoring of patients with GALT deficiency includes determining metabolite levels (galactose 1-phosphate in red blood cells and galactitol in urine) to measure the effectiveness of and adherence to dietary therapy, ophthalmologic examination for the detection of cataracts and assessment of speech, with the possibility of speech therapy if developmental verbal dyspraxia is evident.

Intake of carbohydrates which must be converted to G6P to be utilized (e.g., galactose and fructose) should be minimized. Although elemental formulas are available for infants, many foods contain fructose or galactose in the forms of sucrose or lactose. Adherence becomes a contentious treatment issue after infancy.

The primary treatment goal is prevention of hypoglycemia and the secondary metabolic derangements by frequent feedings of foods high in glucose or starch (which is readily digested to glucose). To compensate for the inability of the liver to provide sugar, the total amount of dietary carbohydrate should approximate the 24-hour glucose production rate. The diet should contain approximately 65–70% carbohydrate, 10–15% protein, and 20–25% fat. At least a third of the carbohydrates should be supplied through the night, so that a young child goes no more than 3–4 hours without carbohydrate intake

In the last 30 years, two methods have been used to achieve this goal in young children: (1) continuous nocturnal gastric infusion of glucose or starch; and (2) night-time feedings of uncooked cornstarch. An elemental formula, glucose polymer, and/or cornstarch can be infused continuously through the night at a rate supplying 0.5–0.6 g/kg/h of glucose for an infant, or 0.3–0.4 for an older child. This method requires a nasogastric or gastrostomy tube and pump. Sudden death from hypoglycemia has occurred due to malfunction or disconnection, and periodic cornstarch feedings are now preferred to continuous infusion.

Cornstarch is an inexpensive way to provide gradually digested glucose. One tablespoon contains nearly 9 g carbohydrate (36 calories). Although it is safer, less expensive, and requires no equipment, this method does require that parents arise every 3–4 hours to administer the cornstarch. A typical requirement for a young child is 1.6 g/kg every 4 hours.

Long-term management should eliminate hypoglycemic symptoms and maintain normal growth. Treatment should achieve normal glucose, lactic acid, and electrolyte levels, and only mild elevations of uric acid and triglycerides.

Xylose isomerase acts to convert fructose sugars into glucose. Dietary supplements of xylose isomerase may improve the symptoms of fructose malabsorption.

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.

There is no known cure, but an appropriate diet and the enzyme xylose isomerase can help. The ingestion of glucose simultaneously with fructose improves fructose absorption and may prevent the development of symptoms. For example, people may tolerate fruits such as grapefruits or bananas, which contain similar amounts of fructose and glucose, but apples are not tolerated because they contain high levels of fructose and lower levels of glucose.

Medical Care

- Treatment may be provided on an outpatient basis.

- Cataracts that do not regress or disappear with therapy may require hospitalization for surgical removal.

Surgical Care

- Cataracts may require surgical removal.

Consultations

- Biochemical geneticist

- Nutritionist

- Ophthalmologist

Diet

- Diet is the foundation of therapy. Elimination of lactose and galactose sources suffices for definitive therapy.

Activity

- No restriction is necessary.

(Roth MD, Karl S. 2009)

Treatment of LPI consists of protein-restricted diet and supplementation with oral citrulline. Citrulline is a neutral amino acid that improves the function of the urea cycle and allows sufficient protein intake without hyperammonemia. Under proper dietary control and supplementation, the majority of the LPI patients are able to have a nearly normal life. However, severe complications including pulmonary alveolar proteinosis and renal insufficiency may develop even with proper treatment.

Fertility appears to be normal in women, but mothers with LPI have an increased risk for complications during pregnancy and delivery.

Individuals presenting with Type III galactosemia must consume a lactose- and galactose-restricted diet devoid of dairy products and mucilaginous plants. Dietary restriction is the only current treatment available for GALE deficiency. As glycoprotein and glycolipid metabolism generate endogenous galactose, however, Type III galactosemia may not be resolved solely through dietary restriction.

To relieve reactive hypoglycemia, the NIH recommends taking the following steps:

- Avoiding or limiting sugar intake;

- Exercising regularly; exercise increases sugar uptake which decreases excessive insulin release

- Eating a variety of foods, including meat, poultry, fish, or nonmeat sources of protein, foods such as whole-grains, fruits, nuts, vegetables, and dairy products;

- Choosing high-fiber foods.

Other tips to prevent sugar crashes include:

- Avoiding eating meals or snacks composed entirely of carbohydrates; simultaneously ingest fats and proteins, which have slower rates of absorption.

- Consistently choosing longer lasting, complex carbohydrates to prevent rapid blood-sugar dips in the event that one does consume a disproportionately large amount of carbohydrates with a meal

- Monitoring any effects medication may have on symptoms.

Low-carbohydrate diet and/or frequent small split meals is the first treatment of this condition. The first important point is to add small meals at the middle of the morning and of the afternoon, when glycemia would start to decrease. If adequate composition of the meal is found, the fall in blood glucose is thus prevented. Patients should avoid rapidly absorbable sugars and thus avoid popular soft drinks rich in glucose or sucrose. They should also be cautious with drinks associating sugar and alcohol, mainly in the fasting state.

As it is a short-term ailment, a sugar crash does not usually require medical intervention in most people. The most important factors to consider when addressing this issue are the composition and timing of foods.

Acute low blood sugar symptoms are best treated by consuming small amounts of sweet foods, so as to regain balance in the body’s carbohydrate metabolism. Suggestions include sugary foods that are quickly digested, such as:

- Dried fruit

- Soft drinks

- Juice

- Sugar as sweets, tablets or cubes.

Weight loss and dietary modification are effective first-line lifestyle modification treatments for hypertriglyceridemia. For people with mildly or moderately high levels of triglycerides lifestyle changes including weight loss and dietary modification are recommended. This may include restriction of carbohydrates (specifically fructose) and fat in the diet. Medications are recommended in those with high levels of triglycerides that are not corrected with the aforementioned lifestyle modifications, with fibrates being recommended first.

The decision to treat hypertriglyceridemia with medication depends on the levels and on the presence of other risk factors for cardiovascular disease. Very high levels that would increase the risk of pancreatitis is treated with a drug from the fibrate class. Niacin and omega-3 fatty acids as well as drugs from the statin class may be used in conjunction, with statins being the main medication for moderate hypertriglyceridemia when reduction of cardiovascular risk is required.

Galactose is converted into glucose by the action of three enzymes, known as the Leloir pathway. There are diseases associated with deficiencies of each of these three enzymes:

At this time there is no treatment for transaldolase deficiency.

There is currently research being done to find treatments for transaldolase deficiency. A study done in 2009 used orally administered N-acetylcysteine on transaldolase deficient mice and it prevented the symptoms associated with the disease. N-acetylcysteine is a precursor for reduced glutathione, which is decreased in transaldolase deficient patients.

Because of the ease of therapy (dietary exclusion of fructose), HFI can be effectively managed if properly diagnosed. In HFI, the diagnosis of homozygotes is difficult, requiring a genomic DNA screening with allele specific probes or an enzyme assay from a liver biopsy. Once identified, parents of infants who carry mutant aldolase B alleles leading to HFI, or older individuals who have clinical histories compatible with HFI can be identified and counselled with regard to preventive therapy: dietary exclusion of foods containing fructose, sucrose, or sorbitol. If possible, individuals who suspect they might have HFI, should avoid testing via fructose challenge as the results are non-conclusive for individuals with HFI and even if the diagnostic administration fructose is properly controlled, profound hypoglycemia and its sequelae can threaten the patient's well-being.

The primary treatment for insulin resistance is exercise and weight loss. Research shows that a low-carbohydrate diet may help. Both metformin and thiazolidinediones improve insulin resistance, but only are approved therapies for type 2 diabetes, not for insulin resistance. By contrast, growth hormone replacement therapy may be associated with increased insulin resistance.

Metformin has become one of the more commonly prescribed medications for insulin resistance. Unfortunately, Metformin also masks Vitamin B12 deficiency, so accompanying sub-lingual Vitamin B12 tablets are recommended.

Insulin resistance is often associated with abnormalities in lipids particularly high blood triglycerides and low high density lipoprotein.

The "Diabetes Prevention Program" (DPP) showed that exercise and diet were nearly twice as effective as metformin at reducing the risk of progressing to type 2 diabetes. However, the participants in the DPP trial regained about 40% of the weight that they had lost at the end of 2.8 years, resulting in a similar incidence of diabetes development in both the lifestyle intervention and the control arms of the trial. One 2009 study found that carbohydrate deficit after exercise, but not energy deficit, contributed to insulin sensitivity increase.

Resistant starch from high-amylose corn, amylomaize, has been shown to reduce insulin resistance in healthy individuals, in individuals with insulin resistance, and in individuals with type 2 diabetes. Animal studies demonstrate that it cannot reverse damage already done by high glucose levels, but that it reduces insulin resistance and reduces the development of further damage.

Some types of polyunsaturated fatty acids (omega-3) may moderate the progression of insulin resistance into type 2 diabetes, however, omega-3 fatty acids appear to have limited ability to reverse insulin resistance, and they cease to be efficacious once type 2 diabetes is established.

Caffeine intake limits insulin action, but not enough to increase blood-sugar levels in healthy persons. People who already have type 2 diabetes may see a small increase in levels if they take 2 or 2-1/2 cups of coffee per day.

Galactosemic infants present clinical symptoms just days after the onset of a galactose diet. They include difficulty feeding, diarrhea, lethargy, hypotonia, jaundice, cataract, and hepatomegaly (enlarged liver). If not treated immediately, and many times even with treatment, severe mental retardation, verbal dyspraxia (difficulty), motor abnormalities, and reproductive complications may ensue. The most effective treatment for many of the initial symptoms is complete removal of galactose from the diet. Breast milk and cow's milk should be replaced with soy alternatives. Infant formula based on casein hydrolysates and dextrin maltose as a carbohydrate source can also be used for initial management, but are still high in galactose. The reason for long-term complications despite a discontinuation of the galactose diet is vaguely understood. However, it has been suggested that endogenous (internal) production of galactose may be the cause.

The treatment for galactosemic cataract is no different from general galactosemia treatment. In fact, galactosemic cataract is one of the few symptoms that is actually reversible. Infants should be immediately removed from a galactose diet when symptoms present, and the cataract should disappear and visibility should return to normal. Aldose reductase inhibitors, such as sorbinil, have also proven promising in preventing and reversing galactosemic cataracts. AR inhibitors hinder aldose reductase from synthesizing galactitol in the lens, and thus restricts the osmotic swelling of the lens fibers. Other AR inhibitors include the acetic acid compounds zopolrestat, tolrestat, alrestatin, and epalrestat. Many of these compounds have not been successful in clinical trials due to adverse pharmokinetic properties, inadequate efficacy and efficiency, and toxic side effects. Testing on such drug-treatments continues in order to determine potential long-term complications, and for a more detailed mechanism of how AR inhibitors prevent and reverse the galactosemic cataract.

Since the conversion of dihydroxyphenylserine (Droxidopa; trade name: Northera; also known as L-DOPS, L-threo-dihydroxyphenylserine, L-threo-DOPS and SM-5688), to norepinephrine bypasses the dopamine beta-hydroxylation step of catecholamine synthesis, L-Threo-DOPS is the ideal therapeutic agent. In humans with DβH deficiency, L-Threo-DOPS, a synthetic precursor of noradrenaline, administration has proven effective in dramatic increase of blood pressure and subsequent relief of postural symptoms.

L-DOPS continues to be studied pharmacologically and pharmacokinetically and shows an ability to increase the levels of central nervous system norepinephrine by a significant amount. This is despite the fact that L-DOPS has a relative difficulty crossing the blood-brain barrier when compared to other medications such as L-DOPA. When used concurrently, there is evidence to show that there is increased efficacy as they are both intimately involved and connected to the pathway in becoming norepinephrine.

There is hope and evidence that L-DOPS can be used much more widely to help other conditions or symptoms such as pain, chronic stroke symptoms, and progressive supranuclear palsy, amongst others. Clinically, L-DOPS has been already shown to be helpful in treating a variety of other conditions related to hypotension including the following:

- Diabetes induced orthostatic hypotension

- Dialysis-induced hypotension

- Orthostatic intolerance

- Familial amyloidotic polyneuropathy

- Spinal Cord Injury related hypotension

Empirical evidence of mild effectiveness has been reported using mineralocorticoids or adrenergic receptor agonists as therapies.

Other medications that can bring relief to symptoms include:

- phenylpropanolamine- due to pressor response to vascular α-adrenoceptors

- indomethacin

Vitamin C (ascorbic acid) is also a required cofactor for the Dopamine beta hydroxylase enzyme. Recent research has shown that vitamin C rapidly catalyzes the conversion of dopamine to norepinephrine through stimulation of the dopamine beta hydroxylase enzyme.

Glucose-galactose malabsorption is a rare condition in which the cells lining the intestine cannot take in the sugars glucose and galactose, which prevents proper digestion of these molecules and larger molecules made from them.

Glucose and galactose are called simple sugars, or monosaccharides. Sucrose and lactose are called disaccharides because they are made from two simple sugars, and are broken down into these simple sugars during digestion. Sucrose is broken down into glucose and another simple sugar called fructose, and lactose is broken down into glucose and galactose. As a result, lactose, sucrose and other compounds made from carbohydrates cannot be digested by individuals with glucose-galactose malabsorption.

Sucrose intolerance can be caused by genetic mutations in which both parents must contain this gene for the child to carry the disease (so-called primary sucrose intolerance). Sucrose intolerance can also be caused by irritable bowel syndrome, aging, or small intestine disease (secondary sucrose intolerance). There are specific tests used to help determine if a person has sucrose intolerance. The most accurate test is the enzyme activity determination, which is done by biopsying the small intestine. This test is a diagnostic for GSID. Other tests which can aid in the diagnosis of GSID but which are not truly diagnostic for the disease are the sucrose breath test, and a genetic test which tests for the absence of certain genes which are thought to be responsible for GSID.

Sucrose (also termed "saccharose") is a disaccharide and is a two-sugar chain composed of glucose and fructose which are bonded together. A more familiar name is table, beet, or cane sugar. It was believed that most cases of sucrose intolerance were to do an autosomal recessive, genetic, metabolic disease. Based on new data patients with heterozygous and compound heterozygous genotypes can have symptom presentation as well. GSID involves deficiency in the enzyme sucrase-isomaltase, which breaks apart the glucose and fructose molecules. When disaccharides are consumed, they must be broken down into monosaccharides by enzymes in the intestines before they can be absorbed. Monosaccharides, or single sugar units, are absorbed directly into the blood.

A deficiency of sucrase may result in malabsorption of sugar, which can lead to potentially serious symptoms. Since sucrose-isomaltase is involved in the digestion of starches, some GSID patients may not be able to absorb starches as well. It is important for those with sucrose intolerance to minimize sucrose consumption as much as possible. Dietary supplements or medications may be taken as a substitute for the enzyme missing or to introduce healthy bacteria into the immune system.

Very little is known about outcomes in DG after early childhood. This is because many infants with DG are born in states where they are not diagnosed by NBS, and of those who are diagnosed, most are discharged from metabolic follow-up as toddlers.

Because it is unclear whether DG has any long-term developmental impacts, or if diet modification would prevent or resolve any issues that may result from DG, any developmental or psychosocial problems experienced by a person with DG should be treated symptomatically and the possibility of other causes should be explored.

Of note, premature ovarian insufficiency, a common outcome among girls and women with classic galactosemia, has been checked by hormone studies and does not appear to occur at high prevalence among girls with DG.

Prior Research Concerning Developmental Outcomes of Children with DG: Three

studies of developmental outcomes of children with DG have been published.

- The first looked at biochemical markers and developmental outcomes in a group of 28 toddlers and young children with DG, some of whom had drunk milk through infancy and some of whom had drunk soy formula. The authors found that galactose metabolites were significantly elevated in the infants drinking milk over those drinking soy. However, all of the children scored within normal limits on standardized tests of child development.

- A second study of developmental outcomes in DG looked at 3 to 10 year olds living in a large metropolitan area and asked whether children diagnosed as newborns with DG in this group were more likely than their unaffected peers to receive special educational services later in childhood. The answer was yes. Specifically, children with DG in this group were significantly more likely than other children to receive a diagnosis of, or special educational services for, a speech/language disorder.

- The final study reported that addressed developmental outcomes in DG was a pilot study involving direct assessments of 15 children, all ages 6–11 years old; 15 had DG and 5 did not. Children in the DG group showed slower auditory processing than did the control group. The DG group also showed some slight differences in auditory memory, receptive language/ listening skills, social-emotional functioning, and balance and fine motor coordination.

Combined,

these studies "suggest" that school age

children with DG "might" be at

increased risk for specific developmental difficulties compared with controls. All

of the relevant studies were limited, however, leaving the question of whether

children with DG are truly at increased risk for developmental difficulties

unresolved. Current reports also leave open the question of whether dietary

exposure to milk in infancy associates with developmental outcomes in DG. More

research is needed to answer these questions.