2025 – PAGE 356 – INBORN ERRORS OF METABOLISM & MISCELLANEOUS METABOLIC DISORDERS

MAPLE SYRUP URINE DISEASE (MSUD AKA BRANCHED-CHAIN KETOACIDURIA)

Maple Syrup Urine Disease (MSUD, AKA branched-chain ketoaciduria) presents EARLY (in the first week) with sweet-smelling urine, tachypnea, and lethargy. If left untreated, it can result in severe neurologic issues in 2–3 weeks, including encephalopathy and seizures. MSUD is the exception amongst this group and DOES have hyperammonemia, ketoacidosis, and hypoglycemia. It can look like an organic acidemia, so be careful! Branched chain amino acids cannot be broken down, so high levels of Valine, Isoleucine, Alloisoleucine, and Leucine are found in the serum. The defective enzyme (complex-branched chain alpha-ketoacid dehydrogenase—just an FYI, low-yield) is also partly responsible for the breakdown of ketones, which is why there is ketosis and ketonuria. Treat with a special diet free of branched-chain amino acids.

• MNEMONIC: HYPOGLYCEMIA occurs because all of the sweetness is in the SWEET-SMELLING MAPLE SYRUP PEE!
• MNEMONIC: Imagine a college named MSU (Maple Syrup University). At MSU, the kids get TACHYPNEIC and TIRED/LETHARGIC during the VERY FIRST WEEK of college because they’re too busy partying. One guy even got hazed this week by some frat guys who gave him a chem class VIAL of URINE with MAPLE SYRUP IN IT. They told him the VIAL was full of beer!
  • KEY: VERY FIRST WEEK = Early Presentation. VIAL = Valine, Isoleucine, Alloisoleucine, and Leucine. Consider using “LEUCI loves her MAPLE SYRUP!” as well.

(DOUBLE TAKE) HOMOCYSTINURIA

Homocystinuria is an aminoacidopathy with physical features that are Marfanoid, but this includes COGNITIVE DEFICITS and neurologic deficits. Also, as in Marfan Syndrome, there can be displacement of the lens. However, the displacement is DOWNWARDS or POSTERIORLY. These patients are hypercoagulable, so there may be a history of DVT. It can be diagnosed by noting high levels of homocysteine in the urine. Treat with pyridoxine or a diet high in cysteine and low in methionine.

MNEMONIC: (Image of Homo erectus) www.pbrlinks.com/HOMOCYSTEINURIA1

MNEMONIC: Imagine a proud and TALL HOMO erectus next to a fire. He suddenly develops CLOTS in his BRAIN that cause him to FALL DOWN face-forward so that he injures his EYES. He now has NEUROLOGIC DEFICITS because of the CLOTS in his brain, and his ocular lens is DOWNWARDLY displaced.

MNEMONIC: This sounds intuitive, but how do you treat someone who is losing an amino acid in their urine? Give them more of it! Treat with cysteine.

TYROSINEMIA (TYPE I)

Tyrosinemia is an aminoacidopathy that is caused by an inability to effectively break down the amino acid tyrosine. It results in liver and kidney disturbances and intellectual disability. Symptoms start in the first few months of life with failure to thrive. There can be liver failure (jaundice) and renal failure (oliguria). Other symptoms include nausea, vomiting, and frequent nosebleeds. The skin and urine can have a “cabbage-like odor.” There is a high risk of liver tumors (hepatoblastoma early in life and hepatocellular carcinoma in late childhood). Treat with a low-tyrosine and low phenylalanine diet. Monitor for kidney and liver damage.

CARBOHYDRATE METABOLISM DISORDERS

DISORDERS OF CARBOHYDRATE METABOLISM

Carbohydrate metabolism disorders include Galactosemia, Hereditary Fructose Intolerance, and Aldolase deficiency. They often result in hypoglycemia, hyperammonemia, acidurias, and organic acidemias.