Kelly McKean, Melissa Edwards

5.1.1 Name of Disorder

Urea cycle defects (UCD).

5.1.2 Clinical Definition

The urea cycle is the enzyme cycle whereby ammonia is converted to urea. Disorders of the urea cycle result from genetic defects in any one of the six enzymes that function in urea production (see nearby table).

5.1.3 How It Is Diagnosed

Increased plasma ammonia. In addition, plasma amino acids and urine organic acids and orotic acid, blood glucose, ketones, anion gap, and pH and CO₂ may be abnormal. Increased plasma citrulline, argininosuccinic acid, and arginine occur in citrullinemia, argininosuccinic acidemia, and argininemia, respectively.

5.1.4 Nutritional Implications

In acute hyperammonemia, protein intake elevates ammonia further. However, over-restriction of protein can result in body protein catabolism and can contribute to hyperammonemia.

Kelly McKean, Melissa Edwards

5.2.1 Name of Disorder

Maple syrup urine disease (MSUD).

5.2.2 Clinical Definition

Disorder of branched-chain amino acid (BCAA) metabolism; block in branchedchain α-ketoacid dehydrogenase complex.

5.2.3 How It Is Diagnosed

Abnormal plasma amino acids (elevated leucine, isoleucine, valine, alloisoleucine) and urine organic acids with abnormal branched-chain hydroxyacids and ketoacids.

5.2.4 Nutritional Implications

Lifelong restriction of leucine, isoleucine, and valine, likely requiring specialized low-protein foods. Supplemental medical formula that is free of BCAAs.

5.2.5 Pearls

• MSUD requires lifelong nutrition therapy.
  
• If MSUD patient is symptomatic (vomiting, lethargic), it is important to proceed immediately with IV hydration before obtaining laboratory results. Start an IV with D10½ normal saline run at 1.5 maintenance rate. If acidotic, give sodium bicarbonate per biochemical genetics team recommendations.
  
• If MSUD patient blood leucine is >800 μmol/L or if clinically indicated (excessive vomiting/neurologic compromise), pharmacy may need to order special total parenteral nutrition (free of branched-chain amino acids).

Nutritional Algorithm for Carbohydrate Metabolism Defects: Galactosemia

Kelly McKean, Melissa Edwards

5.3.1 Name of Disorder

Galactosemia.

5.3.2 Clinical Definition

Classic galactosemia is an inherited disorder of galactose metabolism that results from a defect in the enzyme galactose-1-phosphate uridyltransferase (GALT). The accumulation of galactose-1-phosphate (Gal-1-P) and galactose causes multiorgan disease (liver disease, cataracts, renal tubular dysfunction,

growth failure, and ovarian dysfunction in females). Two other very rare forms of galactosemia exist that are due to deficiency in the enzymes galactokinase or uridine diphosphate-Gal-4-epimerase.

5.3.3 How It Is Diagnosed

Quantification of erythrocyte Gal-1-P and GALT activity. Classic galactosemia shows <1% GALT activity and markedly increased Gal-1-P.

5.3.4 Nutritional Implications

Early intervention with a galactose-restricted diet. No breast-feeding. Give powdered soy infant formula. The goal is to restrict galactose to the lowest amount compatible with a diet that is nutritionally adequate. Despite strict elimination of galactose from the diet, outcome is variable. Ensure adequate calcium and vitamin D intake.

Nutritional Algorithm for Carbohydrate Metabolism Defects: Glycogen Storage Disease (GSD) Types 1a and 1b

Kelly McKean, Melissa Edwards

5.4.1 Name of Disorder

Glycogen storage disease (GSD) types 1a and 1b.

5.4.2 Clinical Definition

The GSDs are caused by deficiencies of enzymes that regulate the synthesis or degradation of glycogen. The enzyme defect between glucose-6-phosphate and glucose blocks both glycogenolysis and gluconeogenesis. GSD type 1a is due to a deficiency of the enzyme glucose-6-phosphatase, normally found in liver, kidney, and intestinal mucosa. GSD type 1b results from a defect in glucose-6-phosphate translocase, affecting transfer of glucose-6-phosphate into the endoplasmic reticulum. Hypoglycemia occurs when exogenous sources of glucose are exhausted.

5.4.3 How It Is Diagnosed

Liver biopsy and DNA analysis. Clinically suspected in individuals with hepatomegaly, growth retardation, bleeding tendency, severe neutropenia (type 1b), hypoglycemia, and increased lactate, uric acid, triglycerides, and transaminases.

5.4.4 Nutritional Implications