Hypoglycemia and inborn errors of fat and carbohydrate metabolism Flashcards
Symptoms of hypoglycemia in infants
Tremors Cyanosis Lethargy Poor feeding Convulsions Or, no symptoms
what is the Normal tolerance of fasting (until BG <70 mg/dL) for Infants 1 week to 1 year
15-18 hours
Glycogen stores last ~4 hours
Elevation of ketones after 12-18 hours
what is the Normal tolerance of fasting (until BG <70 mg/dL) for a 1 year old
24 hours
what is the Normal tolerance of fasting (until BG <70 mg/dL) for a 5 year old
36 hours
Glycogen stores last ~8 hours
Elevation of ketones after 18-24 hours
what is the Normal tolerance of fasting (until BG <70 mg/dL) for an adult
48-72 hours
What is Fructose 1-6 Bisphosphatase Deficiency
- disorder of gluconeogenesis
- severe hypoglycemia after a moderate duration of fasting
- severe lactic acidosis with very low pH and Kussmaul breathing
- treatment: avoid fasting
- fasting tolerance improves some, but adults remain symptomatic with fasting
Glucose 6 phosphatase deficiency (Glycogen storage disease type 1a)
- presents at a few months of age
- short fast hypoglycemia
- hypertriglyceridemia, hyperuricemia, elevated lactate
- large hepatomegaly
- poor growth
what is (GSD 1b) glucose 6 phosphate transporter deficiency,
results in neutropenia and inflammatory bowel disease in addition to the features of 1a
what is the treatment for GSD1 in infants?
G-tube or NG tube for continuous overnight feeds
what is the treatment for GSD1 in for older children
uncooked cornstarch every 4 hours (acts like glycogen in the gut
What should you monitor for in GSD1 patients
gout, pancreatitis, renal insufficiency, liver masses
what is the Tx for GSD1b
granulocyte colony stimulating factor (G-CSF) shots ( to stimulate neutrophil production, colectomy
- allopurinol (for gout)
Describe GSD3: ɑ1-6 glucosidase deficiency
presentation = hepatomegaly, elevated liver enzymes, elevated creatine kinase
- relatively short fast ketotic hypoglycemia
- most patients (85%) have both muscle and liver involvement
- hypoglycemia becomes less common with age and fasting duration is increased
- skeletal myopathy and sometimes cardiomyopathy are progressive
What is the Tx of GSD3: ɑ1-6 glucosidase deficiency
uncooked cornstarch
- early trials of ketogenic diet appear to show efficacy
Describe GSD6 and GSD9
glycogenolysis disorders
deficiencies of glycogen phosphorylase (1-4 glucosidase) and glycogen phosphorylase kinase
how do GSD6 and GSD9 present?
milder hepatic glycogenosis
- hepatomegaly is less severe, hypoglycemia is less severe
- may just present with mild persistent LFT elevations, slow growth
what is the treatment of GSD6 and GSD9
treat with uncooked cornstarch, though many teens and adults do not require treatment
GSD9 can be seen more commonly in boys, why?
X-linked
what is GSD4?
Glycogen Synthesis disorder - > glycogen branching enzyme (GBE) deficiency (catalyzes formation of the 1-6 bond) results in abnormal straight glycogen
how does GSD4 present?
presents with early liver failure (age 1y-6y)
what is the Tx for GSD4
requires liver transplant for treatment
What is GSD0
glycogen synthase deficiency
How does GSD0 present?
- no hepatomegaly
- presents with isolated ketotic hypoglycemia
what are some findings that could clue you to GSD0
post-prandial elevated lactate and serum glucose
what is Hereditary fructose intolerance
deficiency of the enzyme aldolase B, which allows fructose to be metabolized via glycolysis
what is the pathophysiology of Hereditary fructose intolerance
toxic accumulation of fructose 1 phosphate (F1P)
- F1P depletes phosphate (and hence ATP), causing acute liver injury
- F1P inhibits glycogenolysis and gluconeogenesis
WHAT IS THE PRESENTATION OF Hereditary fructose intolerance
- presents with acute liver injury and hypoglycemia when children first consume fructose (typically fruit purees at a few months of age)
what is the Tx of Hereditary fructose intolerance
fructose avoidance
How does Galactosemia present
presents at a few days of age with poor feeding, jaundice, altered mental status, coagulopathy, liver disease, cataracts, E Coli sepsis (specific immune defect)
what is the Tx of Galactosemia
treatment = soy formula for infants, avoidance of lactose for older children
what are some chronic complications that can occur in galactosemia even with galactose avoidance:
learning disability, ovarian failure
_____ is the most common disorder of fat metabolism, children are completely asymptomatic unless fasting
Medium chain acyl CoA dehydrogenase deficiency
what is symptomatic presentation of Medium chain acyl CoA dehydrogenase deficiency (MCADD)
is “Reye-like syndrome” – acute hepatic encephalopathy
- elevated LFTs, elevated uric acid, altered mental status, hypoketotic hypoglycemia
how is Medium chain acyl CoA dehydrogenase deficiency diagnosed and treated
treatment is simply avoidance of fasting
Diagnosis = acylcarnitine profile
what is the presentation of Very long chain acyl CoA dehydrogenase deficiency (VLCADD)
severe neonatal presentation = hypoketotic hypoglycemia, cardiomyopathy, sudden cardiac death due to arrhythmia.
milder presentation = rhabdomyolysis in teens or adulthood
what is the treatment of Very long chain acyl CoA dehydrogenase deficiency (VLCADD)
treatment = restriction of long-chain fats in diet, supplementation of medium chain fats; also (of course) avoidance of fasting
Carnitine deficiency results in a ____
- functional fatty acid oxidation disorder if severe
- is often secondary to diet or depletion due to conjugation and excretion in situations of organic molecule accumulation in the body
- most people with the disorder are asymptomatic, but some have hypoketotic hypoglycemia or cardiomyopathy
primary carnitine deficiency is a disorder of _______
renal re-uptake of carnitine
what is the tx of Carnitine deficiency
carnitine supplementation
In a neonate, measurable serum insulin in the face of hypoglycemia is indicative of ______
hyperinsulinism
what is the treatment for hyperinsulinism
continuous feeds/IVs, diazoxide, octreotide, pancreatic resection
what are other causes of hyperinsulinism
1) exogenous administration
- can check serum C-peptide level to see if it correlates with insulin
2) dumping syndrome
- common in children with G-tube and Nissen fundoplication
3) insulinoma
- hormone-secreting pancreatic tumor, may be associated with a genetic cancer predisposition syndrome
4) Beckwith-Wiedemann Syndrome
- an epigenetic disorder of growth regulation that is often associated with transient neonatal hyperinsulinism
hypopituitarism is often associated with ____
structural brain malformations and optic nerve hypoplasia
infants with hypopituitarism may have _______
prolonged jaundice, and may have eye movement abnormalities
post prandial lactate and glucose elevation = disorder of ______
glycogen synthesis
fasting lactate elevation = disorder of _______
gluconeogenesis
low ratio of ketones to free fatty acid = _______ disorder
fatty acid oxidation
