Disorders of Carbohydrate Metabolism

00:01 Let's start with disorders of carbohydrate metabolism.

00:05 We can see patients with problems in glucose metabolism, fructose metabolism, and galactose metabolism.

00:14 I've drawn here the galactose differently than glucose because the OH group goes off in a different direction.

00:20 It's a cartoon but I think it's effective.

00:23 Glycogen storage diseases are probably the most common issue around glucose metabolism.

00:29 Essentially, enzyme defects in glycogen breakdown result in an inability to make glucose after a short period of fasting in the liver and the muscle.

00:42 So patients can present with both hepatic disease and muscle disease.

00:46 In other words, they're having a problem getting the glucose out of their glycogen stores.

00:52 With hepatic disease, a short fast can cause hypoglycemia.

00:58 It usually shows up in the first 6 months of life as children start to space out their feeds.

01:05 Typically, a newborn baby is eating every 2 hours, the glycogen storage aren't that important.

01:10 As they get older, they rely on their glycogen storage more because they're going longer distances between feeds.

01:17 These patients can present with muscle weakness and they can present with hepatic cirrhosis at times.

01:24 The muscle disease is a progressive muscle weakness and sometimes can involve the heart as well.

01:31 And in some varieties of glycogen storage diseases, the cardiomyopathy is the most important thing.

01:38 Any child with cardiomyopathy is primarily gonna present with fatigue.

01:42 Let's go through three really common glycogen storage diseases.

01:48 The first one is Von Gierke's disease.

01:51 And I like to think about Von Gierke's as primarily in the liver.

01:56 This is also glycogen storage disease type 1.

01:59 These patients will present with a profoundly challenging hypoglycemia.

02:04 They will have hepatomegaly from their liver involvement.

02:07 They will develop hyperlipidemia as well.

02:10 Because of their underlying problem, they may have growth failure but they will not primarily have weakness.

02:17 Most of their diseases related to the liver.

02:20 That's as opposed to Pompe's disease.

02:24 Pompe's disease can be very severe in childhood or it can develop later.

02:30 But this is glycogen storage disease type 2 and it's primarily involving the heart.

02:36 They do not develop hypoglycemia.

02:39 They still do get some hepatomegaly but it can either be very severe with a inevitable death by the age of 2 or can be more benign.

02:51 Clearly, a heart failure is the most important heralding symptom of Pompe's disease.

02:56 The last example would be McArdle's and when I think of McArdle's I think of muscle.

03:02 Muscle McArdle's.

03:03 This is glycogen storage disease type 5.

03:07 It really only has muscle involvement, so these patients develop the weakness but not as much of the other symptoms.

03:15 They may develop renal problems from myoglobin breakdown and sledging in the kidney causing renal damage, so monitoring for that is important.

03:25 Let's switch to another type of sugar which is galactosemia.

03:31 Remember that galactose is metabolized through a pathway involving two major enzymes.

03:38 Galactose is turned into galactose 1 phosphate through galactokinase.

03:44 Galactose 1 phosphate has that enzyme GALT which then turns it into glucose 1 phosphate and then we can metabolize the galactose.

03:53 Remember that the galactose, the sugar in milk, is a galactose plus a glucose stocked together.

04:00 Lactase breaks those apart and then for the galactose, we use this pathway to metabolize it.

04:06 In patients with galactosemia, they have a defect in one of these two enzymes.

04:11 Galactokinase deficiency is very rare, we almost never see it.

04:17 Those children typically have a milder course.

04:20 But GALT deficiency is not too uncommon, and we do see periodically patients with GALT deficiency.

04:27 GALT deficiency usually presents once milk is introduced.

04:33 As you can imagine, milk is introduced essentially right at birth.

04:37 So we screen for galactosemia in the newborn screen so that we can prohibit the child from getting milk once they're born if they have this problem.

04:49 We need to give them a special formula that does not have galactose in it.

04:55 Patients where they are not picked up will develop failure to gain weight, vomiting, lethargy, jaundice, hypoglycemia, and this is key for your exam, cataracts.

05:09 Exams love to mention cataracts.

05:11 These children can also develop renal failure.

05:14 So obviously, screening for these diseases is very important.

05:18 Even if effectively picked up on the newborn screen and a rapid intervention is made, these children can still have problems over time.

05:28 They can develop speech delay, ataxia, gonadal failure, problems can happen.

05:33 But their course is much better if we can make a dietary intervention early in life.

05:38 Very rare, but we can see hereditary fructose intolerance as well.

05:44 This generally presents once fruit is introduced.

05:47 These children can't metabolize fructose well.

05:50 They generally would develop an increased pyruvate and lactate which leads to a metabolic acidosis.

05:57 These children can develop abdominal pain, nausea, vomiting.

06:00 They can have a severe hypoglycemia as well, which ironically, is not relieved by a fruit juice.

06:06 They can develop lethargy, seizure, and diarrhea.

06:11 So these children really need to avoid fructose in their diet.