Clinical Features
- FTT, vomiting, diarrhea
-patients present with hypoglycemia and encephalopathy shortly after birth, followed by jaundice, ascites, hepatomegaly and liver failure
- +/- hemolytic anemia, cataracts, renal dysfunction
MANAGEMENT/TREATMENT
- elimination of dietary galactose
-Switch infants to soy or hydrolyzed formula
-Older children and adults should avoid products that contain milk
-Certain legumes (garbanzo and black beans) contain high galactose and should be avoided
-Calcium and Vit D supplementation
-Annual ophtho. and neurodev. exams are recommended
Definitive diagnosis requires tissue enzyme assay
Type II (Pompe Disease)
- acid-α-glucosidase deficiency
- mainly affects heart and muscle
- presents with cardiorespiratory failure and/or cardiomyopathy
Type III (Forbes Disease)
- deficient debranching enzymes
- Liver, muscle
- hepatomegaly, fasting hypoglycemia, hyperlipidemia, progressive myopathy
Type IV (Andersen's Disease)
- defect in α-1,4-glucan 6 glucosyl-transferase (branching enzyme)
- Liver
- HYPOGLYCEMIA IS RARE
- liver disease and cardiomyopathy are common
GSD Type I
- continuous glucose source (small frequent feeds in infants, continuous or overnight enteric tube feeds, constarch
- allopurinol and lipid lowering agents are rarely needed
- recombinant G-CSF for neutropenia
GSD Type III
- continuous glucose source
- annual AFP and ultrasound due to increased risk of hepatocellular adenomas
- annual echo and EKG for patients with cardiomyopathy
GSD Type IV
- Liver transplantation is the only effective therapeutic modality for these patients
Shortly after birth, a 3,500 g term newborn is found to be jittery and to have a high-pitched cry.
Physical examination reveals tachypnea and a liver edge that is palpable several centimeters below
the umbilicus. Blood glucose concentration is 14 mg/dL. Among the following, the MOST likely cause
of the hypoglycemia in this newborn is:
A. Galactokinase deficiency
B. Glycogen storage disease
C. Insulinoma
D. Maternal diabetes mellitus
E. Prolonged maternal labor
Type Ia (Von Gierke Disease)
- defect in Glucose-6-phosphatase
- affects mainly liver and kidney
- "Classic form of GSD"
- hypoglycemia and acidosis 3-4 hrs post meal; hepatomegaly with protuberant abdomen; elevated TGs; Doll Facies and xanthomas; impaired platelet function/bleeding; elevated uric acid
Type Ib and Ic
- Glucose - 6 - phosphatase related transport
- mainly affects liver
- Ib: neutropenia and recurrent infections associated with IBD
- Ic: impaired insulin secretion
Common Features of Disorders of CHO Metabolism
Glycogen Storage Diseases
- Neonates & Infants may present with hypoglycemia, vomitting, diarrhea, poor feeding, poor weight gain, seizures, hepatomegaly and liver failure
- Older children may present with hepatomegaly, abnormal feeding behaviors, poor weight gain and growth, and developmental delay
- Caused by deficiencies of enzymes in the pathways of glycogen metabolism
- 10 different types of GSD have been identified
- Types I, III, IV, and VI primarily affecting the liver
Diagnosis is via liver biopsy for Type I; and molecular genetics for Types I through V
Most often, patients present after an acute illness, systemic stressor or prolonged period of fasting
Managment/Treatment
Carbohydrate Metabolism
Metabolic Liver Diseases -
Disorders of Carbohydrate Metabolism
- Glucose Homeostasis - Central role of the liver
- Gluconeogensis
- Glycogen breakdown
- Dietary CHOs include glucose, galactose, fructose
- Glucose typically stored as glycogen (branched polymer)
Hereditary Fructose Intolerance
- Deficiency of Fructose 1,6-bisphosphonate aldolase (aldolase B)
- 1 in 20k live births, autosomal recessive
Disorders of Galactose Metabolism
Galactosemia
Clinical Features
Management/Treatment
-complete avoidance of fructose and sucrose
-in acutely ill patients, correct hypoglycemia, metabolic acidosis and coagulopathy
- deficiency of galactose 1-phosphate uridyl transferase (GALT)
- 1 in 30-50k live births
- Autosomal-recessive
- Symptoms develop once fructose is introduced into the diet ie sucrose based formula
- most common symptoms include poor feeding, vomiting, diarrhea and abdominal pain
- chronic exposure or large fructose load > seizures, FTT, liver failure, kidney dysfunction
Fructose 1,6-Bisphosphatase Deficiency
- AR condition resulting in impaired gluconeogenesis
- F > M (1.5:1)
- symptoms develop when glycogen stores are low (newborn period or prolonged fasting)
- 50% patients develop symptoms after birth
- definitive diagnosis is made via liver biopsy
- treatment is same as for HFI and avoiding prolonged periods of fasting
DIAGNOSIS
- NBS
- Positive urinary reducing substances without glucosuria
- decrease GALT activity in RBCs