2025 – PAGE 350 – INBORN ERRORS OF METABOLISM & MISCELLANEOUS METABOLIC DISORDERS

GALACTOSEMIA (PEARLS)

Galactosemia is caused by galactose-1-phosphate uridyltransferase deficiency, or GALT deficiency. Lactose breaks down into glucose and gaLactose. Due to the GALT deficiency, galactose-1-phosphate cannot be broken down. Look for an elevated galactose-1-phosphate level in the serum or tissues (builds up in the liver, kidney, and brain). You can also look for decreased GALT activity in RBCs. Patients often present with gram-negative rod sepsis (especially E. coli) before the diagnosis is even made. Treat with a LACTOSE- and a gaLACTOSE-free diet.

HYPERGLYCINEMIA (PEARLS)

Hyperglycinemia findings include an acute encephalopathy, possible hiccups, seizures with a mention of “burst suppression” on EEG, and all normal labs.

NEWBORN SCREEN (NBS)

The standard newborn screen (NBS) includes testing for phenylketonuria (PKU), hypothyroidism, sickle cell anemia, and galactosemia in EVERY U.S. state and in Puerto Rico.

AMMONIA LEVEL

A normal ammonia level is < 50. For urea cycle disorders, look for a VERY high level.

URINARY REDUCING SUBSTANCES

This is an old test that looks for sugars in the urine to screen for possible inborn errors of carbohydrate metabolism. In many labs, all pediatric urine samples with no glucose found on dipstick will reflexively check for other sugars in the urine with this test. The specificity is poor, newborn screens are better for detecting possible inborn errors, and additional, confirmatory testing is needed if this test is positive.

INHERITANCE PATTERN

Most of these diseases are autosomal recessive. Hunter and Ornithine Transcarbamylase are two exceptions.

MNEMONICS: “X marks the spot” for a Hunter. Ornithine transcarbamylaX is how you should pronounce it from now on. Hurler’s is autosomal recessive. Remember, “PAT HAS WACK GAS that makes me HURL in the BACK SEAT of an AUTOmobile” from the Genetics section?

ORGANIC ACIDEMIAS

ORGANIC ACIDEMIAS OVERVIEW

Organic acidemias are caused by enzyme deficiencies that lead to difficulty in breaking down certain organic acids from particular amino acids and fatty acids. Virtually every lab mentioned above will be abnormal. Look for a METABOLIC ACIDosis + KETOSIS + Lactic ACIDosis ± Hyperammonemia (due to a mild effect on urea cycle) ± elevated bilirubin. Patients can also have thrombocytopenia and granulocytopenia (WBC may be low). These patients present EARLY, at about DOL 2. Diagnose by obtaining URINE organic acid levels. Treat immediately with HYDRATION, stopping protein intake, and giving IV glucose and ammonia scavengers (like sodium benzoate). Longer term, prescribe a low protein diet and L-CARNITINE to replace depleted stores and help get rid of the built-up organic acids. Some of the disorders include Isovaleric ACIDemia, Glutaric ACIDemia, Methylmalonic ACIDemia (MMA), and Propionic ACIDemia.

• PEARL: Anytime you see evidence of an ACIDosis in the vignette, and the word ACID in an answer choice (e.g., Isovaleric ACIDemia), start looking for evidence to support this diagnosis. Of course, they could always leave out names and just expect you to choose a diagnostic test or treatment. Isovaleric acidemia is the one more likely to be tested. Also, anytime you see an abnormally HIGH respiratory rate, assume there is a metabolic acidosis! That may be the only clue they give you.
• MNEMONIC: Imagine going grocery shopping for ORGANIC food at a Whole Foods store. As you walk by the TOILET PAPER (TP) section, you look down and notice a piece of tile that has a beautiful white KITE ON IT. You then slip because the floor is wet due to AMMONIA cleaner that the janitor forgot to wipe up. Your head hits the tile with the white KITE ON IT, and you bleed all over the beautiful design. Your blood forms the shape of 2 DOLLS playing with KITES. A manager comes and wraps your head with TP/TOILET PAPER. He then tries to clean the white KITE with his secret formula of white LACTaid milk + white GRANULATED SUGAR.
  • KEY: TP/TOILET PAPER = Thrombocytopenia. KITE ON IT = Ketosis/Ketones. AMMONIA = Possible 2 DOLLS = Presentation by DOL 2. LACTaid milk = Lactic Acidosis. GRANULATED sugar = Granulocytopenia with possible leukopenia (WBC). SUGAR = Hypoglycemia.