2025 – PAGE 357 – INBORN ERRORS OF METABOLISM & MISCELLANEOUS METABOLIC DISORDERS

GALACTOSEMIA (AKA GALACTOSE-1-PHOSPHATE URIDYLTRANSFERASE DEFICIENCY or GALT DEFICIENCY)

Galactosemia is caused by galactose-1-phosphate uridyltransferase deficiency, or GALT deficiency. It can look like an early version of lactase deficiency and can present with vomiting and diarrhea. The more serious symptoms include lethargy, hepatomegaly, jaundice, hypoglycemia, and seizures. Also, patients often PRESENT with gram-negative rod sepsis or meningitis (especially E. coli) before the diagnosis is even made. As a reminder, lactose breaks down into glucose and gaLactose. Due to the enzyme deficiency mentioned, galactose-1-phosphate cannot be broken down. Lactose is in breast milk and formulas, so this presents EARLY (within the first week). Test for an elevated galactose-1-phosphate level in the serum or tissues (builds up in the liver, kidney, and brain). You can also test for decreased GALT activity in RBCs. You can also test for non-glucose reducing substances in the urine. Treat with a LACTOSE- and gaLACTOSE-free diet, such as SOY MILK (the primary carbohydrate in soy milk is sucrose or corn syrup). Untreated galactosemia will result in CATARACTS (within 2-3 weeks of age), severe cognitive defects/intellectual disability, and liver disease.

MNEMONIC: Since patients must have a lactose-free diet, they cannot have any LACTOSE-containing milk that comes from LACTATING breasts (cow or human). Soy is fine. So that means SOY is good for patients with galactoSOYmia.

HEREDITARY FRUCTOSE INTOLERANCE

Children with hereditary fructose intolerance (AKA Fructosemia) can present with vomiting, seizures, HYPO­glycemia, hepatomegaly, or jaundice after eating meals with high fructose or sucrose (which breaks down into glucose and fructose). They are unable to break down fructose and often develop a tendency to AVOID SWEETS. Look for a child who has a SEIZURE right after eating. Treat with a low-fructose diet.

LYSOSOMAL STORAGE DISEASES

PEARL/MNEMONIC: The made-up word “HuNiTaG” can help you remember the names of the most common lysosomal storage diseases tested by the American Board of Pediatrics: Hurler, Hunter, Niemann-Pick, Tay-Sachs, and Gaucher. So, if you’re sure it’s a lysosomal storage disease on the exam but forget which disease is which, maybe this will help you make a better guess.

MUCOPOLYSACCHARIDOSES (MPS)

Hurler Syndrome (AKA Hurlers Syndrome) and Hunter Syndrome (AKA Hunters Syndrome) are the mucopolysaccharidoses (MPS) to DEFINITELY KNOW. The MPS disorders are due to a missing or dysfunctional lysosomal enzyme needed to break down a long carbohydrate (glycosaminoglycans). This results in the accumulation of dermatin, keratin, and heparin sulfate in the brain, bones, connective tissue, and other organs. Since this is an accumulation/deposition disease, it takes time to present. Look for PROGRESSIVE physical deformations and cognitive problems. Also look for coarse features, thick eye­brows, organomegaly, progressive joint contractures, growth deceleration, and even progressive deaf­ness. It’s diagnosed by showing excessive urine mucopolysaccharides. Note that they are all autosomal recessive except for Hunter’s syndrome. Many of the features are the same for these diseases. See below for some of the unique features of each:

• PEARL: Hurler and Hunter syndromes are the ones most likely to be tested.
• HURLER SYNDROME (AKA MPS I or HURLER’S SYNDROME): Children have growth deceleration, coarse facial features, CORNEAL CLOUDING, hepatosplenomegaly, pes cavus (high plantar arches), and hirsutism.
  • IMAGE: www.pbrlinks.com/HURLER1 (coarse features, thick eyebrows).
  • MNEMONIC: Please refer to the “PAT HAS WACK GAS that made me HURL” mnemonic to remind yourself that this is an autosomal recessive disorder. The next part could be, “I HURLED so hard that I WENT BLIND!” (from corneal clouding)
• HUNTER SYNDROME (AKA MPS II or HUNTER’S SYNDROME): Look for a child with coarse facial features, skeletal anomalies, and growth deceleration who has evidence of an X-LINKED disorder (affected maternal uncles). There is NO corneal clouding.
  • IMAGE: www.pbrlinks.com/HUNTER1
  • PEARL: Since this is the only one that’s X-linked, it’s a very “testable” area for the pediatric boards. Use the mnemonics to nail down the inheritance patterns to make sure you don’t get the names confused.
  • MNEMONIC: “X” marks the spot for a HUNTER. Now imagine a HUNTER with GOOD VISION who is SHORT and has an abnormal SPINE that helps him go through the jungle unseen. He’s extremely skilled and always makes the kill by aiming for an “X” on his prey’s forehead.

• SANFILIPPO SYNDROME(MPS III): Progressive reduction in cognitive abilities.
• MORQUIO SYNDROME(MPS IV): Skeletal involvement, corneal clouding but normal intelligence.
• I-CELL DISEASE: This is a mucolipidosis(don’t memorize these long words!), but it has features very similar to HURLER syndrome. Patients can have coarse facial features, corneal clouding, skeletal problems, hip dislocation, club feet, joint contractures, hepatomegaly, or splenomegaly.
  • PEARL: The I is for inclusion-cell disease. If they mention “inclusion,” pick this. Otherwise, you’re probably better off picking Hurler.