TREATMENTPresented by:Omosanyin-Williams, OlabisiPolido, Helen JanePecson, Mark DavidRabang, Jose Mari AntonioMed-I A

MANAGEMENT (CAH)Patients with dehydration, hyponatremia, or hyperkalemia and a possible salt-wasting form of adrenal hyperplasia should receive an intravenous (IV) bolus of isotonic NaCl solution (20 mL/kg or 450 mL/m2) over the first hour, as needed, to restore their intravascular volume and blood pressure if the patient is hypoglycemic , dextrose must be administered and must be included in the rehydration fluid after the bolus dose to prevent hypoglycemia.

The goal of therapy:

glucocorticoid and mineralocorticoid replacement

GOALS OF GLUCOCORTICOID REPLACEMENTto replace the body's requirement for glucocorticoids under normal conditions and during stress and

(2) to suppress ACTH secretion, thereby reducing the stimulus for the adrenal glands to overproduce adrenal androgens in virilizing forms of congenital adrenal hyperplasia

long-term glucocorticoid replacement must be balanced to prevent symptoms of adrenal insufficiency while still allowing the child to grow at a normal rate and prevent symptoms of glucocorticoid excessgeneral average dosage is 10-25 mg/m2/d of hydrocortisone PO divided in 2-3 doses.

Surgery.Reconstructive surgery is recommended for infant girls who have ambiguous external genitalia to correct the appearance and functions of the genitalmay involve reduction of the clitoris size and reconstruction of the vaginal openingtypically performed between 2 and 6 months of age

FOLLOW UPClosely monitor patients with adrenal hyperplasia for adequacy of dosing of glucocorticoids, mineralocorticoids, or both.Too little glucocorticoid results in symptoms of adrenal insufficiency (eg, anorexia, nausea, vomiting, abdominal pain, asthenia) and progressive virilization and advancement of skeletal maturation in virilizing forms.

Too much glucocorticoid results in excess weight gain, Cushingoid features, hypertension, hyperglycemia, cataracts, and growth failure

MANAGEMENT (CONGENITAL HYPOTHYROIDISM)The mainstay in the treatment of congenital hypothyroidism is early diagnosis and thyroid hormone replacementOptimal care may includes diagnosis before age 10-13 days and normalization of thyroid hormone blood levels by age 3 weeks

TREATMENT Levothyroxine established as safe, effective, inexpensive, easily administered, and easily monitoredParents should be provided the hormone in pill form and taught proper administration. The pills can be: crushed in a spoon; dissolved with a small amount of breast milk, water, or other liquid immediately before administrationadministered to the child with a dropper. *pills should not be mixed in a full bottle of formula

Clinical parameters should include linear growth, weight gain, developmental progression, and overall well-being.Laboratory measurements of T4 (total or free T4) and TSH should be repeated 4-6 weeks after initiation of therapy, then every 1-3 months during the first year of life and every 2-4 months during the second and third years

Parents should be educated regarding their child's disorder, the potential problems associated with no treatment or inadequate treatment, and the benefits of early and appropriate treatmentThis should include instructions on the proper administration of the medication and how and when to follow up with the physicianWhen inborn errors of thyroid hormone production are suspected, genetic counseling should be provided

GALACTOSEMIA

Because of newborn screening for galactosemia, patients are being identified and treated early.Elimination of galactose from diet reverses growth failure and renal and hepatic dysfunction.Cataracts regress, and most patients have no impairment of eyesight. Early diagnosis and treatment have improved the prognosis of galactosemia; however, on long-term follow-up, patients still manifest ovarian failure with primary or secondary amenorrhea, developmental delay, and learning disabilities that increase in severity with age.

MAPLE SYRUP URINE DISEASE

Treatment is aimed at hydration and quick removal of the branched-chain amino acids and their metabolites from the tissues and body fluids. Because renal clearance of these compounds is poor, hydration alone may not produce a rapid improvement. Peritoneal dialysis or hemodialysis is the most effective mode of therapy in critically ill infants and should be instituted promptly; significant decreases in plasma levels of leucine, isoleucine, and valine are usually seen within 24 hr of institution of treatment.Providing sufficient calories and nutrients intravenously or orally should reverse the patient's catabolic state.

Treatment after recovery requires a diet low in branched-chain amino acids. Synthetic formulas devoid of leucine, isoleucine, and valine are available commercially. Because leucine, isoleucine and valine cannot be synthesized endogenously, small amounts of them should be added to the diet; the amount should be titrated carefully by performing frequent analyses of the plasma amino acids. Patients with MSUD should remain on the diet for the rest of their lives. Liver transplantation has been performed in a small number of patients with classic MSUD with promising results. These children have been able to tolerate a normal diet.

PhenylketonuriaCritical!Before 3 wks of age diagnosis and initiation of dietary treatment of classic PKU prevent mental retardation

Screening (North America, Australia, Europe)determination of blood phenylalamine levelsConfirmed by:Using quantitative analysis of plasma amino acids

Diet: phenylalanine restriction (if blood phenylalanine level is >300 umol/L (5mgdL)

Treatment: special diet low in phenylalanine and supplemented with tyrosine (tyrosine becomes an essential amino acid in phenylalanine hydrosylase deficiency)

Plasma phenylalanine contration (60-360 umol)

TetrahydrobiopterinEssential cofactor of phenylalanine hydroxylaseIncrease tolerance to dietary protein and enhance metabolic control

During pregnancy:In women with PKU, phenylalamine levels should be strictly controlled to prevent congenital defects and microcephaly in the offspringIf failed to do so:the child/ren will have severe mental and growth retardation

*Phenylalanine-restricted diet should be instituted two months prior to conception and throughout course of gestation

Type I Glycogen Storage Disease(Galactose 6 Phosphatase or Translocase Deficiency/ von Gierkes disease)Maintain normal blood glucose:continuous infusion of glucose via feeding tube or oral administration of uncooked conrnstarch serves as a slow-relaease form of glucose (1.6g/kg every 4H for infants

Dietary supplements of multivitamins, calcium, Vit. D often required

Allopurinol: given to lower uric acid lvlsStatins/ Fibric acids: reduce hyperlipidemiaACE-I: treatment of microalbuminuriaCitrate supplementation: prevent nephrocalcinosis and development of urinary calculi

Orthotrophic Liver transplantation Reserved for GSD I patients with liver malignancy, multiple liver adenomas, metabolic derangements refractory to medical management, liver failure

Type III Glycogen Storage Disease(Debrancher deficiency/ Limit dextrinosis)Diet: less demanding than type IFrequent high-carbohydrate meals with cornstarch supplements

Nocturnal Gastric Feeding effective in treating hypoglycemia

High protein diet recomemdedWhy? Neogenesis is intact in GSD III serves alternative source for glucose

Pompe DiseaseThe accumulation of glycogen in certain tissues, especially muscles, impairs their ability to function normally. This can be life-threatening when the breathing and heart muscles are affected.

TreatmentManagement of Pompe disease includes a combination of disease-specific treatment and supportive regimens.Disease-specific treatmentenzyme replacement therapy (ERT) for Pompe disease (Myozyme) was approved in the USA, Europe, and Canada, with subsequent approval in countries around the world. (In the US, Myozyme is for patients younger than 8 years, and Lumizyme is for patients older than 8 years of age), recommended every two weeks via intravenous administration of recombinant human acid a-glucosidase at a dose of 20 mg/kg body weight.

Supportive Regimens patients with Pompe disease have a wide range of clinical manifestations and functional impairment, they are best followed by amultidisciplinary team.Respiratory support: one of the most important aspects of Pompe management, as most patients have some degree of respiratory compromise and respiratory failure, is the most common cause of death in children and adults with the disease. Physical therapy, non-invasive or invasive ventilatory support

Physiotherapy: stabilizing or improving physical ability. Physiotherapy, in conjunction with ERT, can help to alleviate or prevent secondary complications, such as reduced bone mineral density and contractures.Nutrition: patients with Pompe disease have trouble gaining and/or maintaining weight. high-calorie diets, as well as on strategies to change the size and texture of food to make it easier to eat and to reduce the risk of aspiration recommended. Nasogastric or nasoenteric tube feeding may be called for if patients are at high risk for aspiration, more common in infantile-onset patients due to severe muscle weakness, ventilator dependency, and macroglossia.

Thanks for listening!

Extraordinary Measures is a touching movie released in January of 2010 about one familys experience with Pompe disease. The movie is based on the true story of New Jersey entrepreneur John Crowley -- played by Brendan Fraser -- who raised millions in capital and started a biotech company to develop a life-saving drug for his two young children, both of whom suffer from Pompe disease.

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