2025 – PAGE 355 – INBORN ERRORS OF METABOLISM & MISCELLANEOUS METABOLIC DISORDERS

GLYCOGEN STORAGE DISEASE DUE TO ALDOLASE A DEFICIENCY

This long-named disease is also called Glycogen Storage Disease XII (GSD12)  and is characterized by hemolytic anemia, possible myopathy and possible intellectual deficit. The myopathy can be so severe that it can trigger a fatal rhabdomyolysis.

• PEARL: A family history of episodic rhabdomyolysis should make you think of this condition.

AMINOACIDOPATHIES

NOTE: Aminoacidopathies are disorders in which isolated amino acids cannot be broken down. Since the problem is limited to only a particular amino acid, there is no significant elevation in ammonia levels (the exception is MSUD). Also, there is no acidosis because this is not a fuel issue (carbohydrate and fat metabolism are working fine, but once again MSUD is the exception). The disorders include Phenylketonuria (PKU), Alkaptonuria, Maple Syrup Disease (MSUD), Homocystinuria, and Tyrosinemia.

PHENYLKETONURIA (PKU)

Phenylketonuria (PKU) is a deficiency of phenylalanine hydroxylase, so phenylalanine can’t be broken down into tyrosine. Patients are noted to have a musty/mousy odor and LIGHT-colored skin and hair. If left untreated, patients will be asymptomatic for a few months. They can then start to present with developmental delay, the musty/mousy odor, skin changes (light skin/hair, possible eczema like rash), and eventually might even carry a diagnosis of “autism” because of severe intellectual disability. The disease is also associated with septal defects. All states test for this on the newborn screen, which looks for an elevated phenylalanine level. Your first step in a neonate should be to REPEAT testing because some kids have a TRANSIENT elevation in their phenylalanine level. If it’s abnormal again, the child still might be okay because it may just be that the enzyme hasn’t matured yet. Consult a geneticist to sort it out. The goal should be to start treatment by 14 days of life; otherwise severe intellectual disability can occur. For kids with PKU, TYROSINE levels will be low (or nonexistent), so tyrosine becomes an essential amino acid. Some children require Tyrosine supplementation in the diet. The general treatment, though, is a LOW PHENYLALANINE DIET. OVER-TREATING (meaning zero phenylalanine) can result in lethargy, rash, and diarrhea (don’t get it confused with pellagra!). Also, if a pregnant patient has poor dietary control, her child can be born with microcephaly, congenital heart defects (CHD), and cognitive defects.

PEARL: Look for a child who looks like s/he might have albinism. Also, keep in mind that the newborn screen is only valid AFTER protein intake.

MNEMONIC: Imagine walking into a smelly basement. You say, “PEE-YEW!” Just then you see a LIGHT-SKINNED MOUSE with WHITE HAIR running by. You scream, “EEW!” and run away.

• KEY: PEE-YEW = PKU. LIGHT COLORS = Light skin and hair. EEW = PKU again. You could consider adding a TYRE (for tyrosine) to the story, and imagine that the mouse runs out of an old tire in the corner.

ALKAPTONURIA (AKA ALCAPTONURIA)

Alkaptonuria (AKA alcaptonuria) is a problem with phenylalanine AND tyrosine metabolism. Can present with “black” urine in a diaper since urine turns dark after long exposure to air. There is excess homogentisic acid, which can deposit in joints and on heart valves. Check for elevated homogentisic acid levels in urine. Treat by limiting intake of phenylalanine and tyrosine.

MNEMONIC: Instead of ALKAPTONURIA, rename it to “ALL-BLACK-TONED-URIA!”