2025 – PAGE 260 – GENETICS & INHERITED DISEASES
(DOUBLE TAKE) CHRONIC GRANULOMATOUS DISEASE (CGD) = SERRATIA
Chronic Granulomatous Disease (CGD) is an X-linked recessive disorder. On the boards, if you see a boy diagnosed with Serratia, he’s probably got CGD. CGD is the result of deficiency of an enzyme within neutrophils that is needed to destroy cell walls and aid in phagocytosis. Chemotaxis is intact. This is not a cell line deficiency, so there is NO LYMPHOpenia and NO NEUTROpenia. This is a functional/oxidative burst issue. The immune system is unable to destroy certain bacteria and fungi (Aspergillus, Candida, E. coli, Serratia and Staphylococcus) because they are all catalase positive organisms. The organisms/infections are usually considered to be low-grade. Patients may have liver abscesses, osteomyelitis, recurrent lymphadenitis, and recurrent skin infections. They can also have GI infections and granulomas of the skin, GI, or GU tract.
- DIAGNOSIS: The preferred test is Dihydrorhodamine Fluorescence (DHR), followed by the Nitroblue Tetrazolium (NBT) dye test.
- TREATMENT: Life-long prophylaxis with antibacterial antibiotics, anti-fungal medications and interferon-gamma. Infections should be treated early and aggressively.
- PEARL: Like the name says, it’s a “CHRONIC” condition. Children usually present by 5 years of age.
- MNEMONIC: CGD = This is an X-linked disorder, ChroniX GranulomatuX Disease. Put an X where it makes sense for you to remember this key fact.
MNEMONIC: NEUTROphil disorder = NEUTROBLUE tetrazolium test, which tests for the NEUTROglycerin oxidative BURST.” ChroniX GranulomatuX Disease seems to be all about colors! BLUE and SERRATIA (RED)!!!
(DOUBLE TAKE) DUCHENNE MUSCULAR DYSTROPHY (DMD)
Duchenne muscular dystrophy is an X-linked disorder (located at Xp21 – low yield) that causes a deficiency in the muscles’ DYSTROPHIN protein. Children are usually wheelchair-bound by 7 or 8 years of age and are unable to walk by their 13th birthday. They can have severe scoliosis, and the major cause of morbidity (and mortality) is the involvement of respiratory muscles. Children have a poor cough and frequent pneumonias. The heart can also be involved (cardiomyopathy). Other symptoms include toe walking, a waddling gait, use of the Gower maneuver to stand, pseudohypertrophy of calf muscles from fatty/fibrous tissue deposition, and poor head control. Start your workup with a CK level (like Dermatomyositis) since it’s ALWAYS elevated. If high, refer to a neurologist for further workup. Electromyogram (EMG) studies can support the diagnosis but are not definitive. Genetic testing (such as multiplex PCR) may provide a definitive diagnosis. If it does not (because of an unknown mutation site), then proceed to a muscle biopsy.
PEARLS: Though it’s an X-linked disorder, there is a very HIGH rate of spontaneous mutations, so the mom does not have to be a carrier, and there does NOT have to be a positive family history. If the mom is a carrier, though, she can have elevated CK levels even though she has no symptoms.
PEARLS: There can be varying degrees of nonprogressive cognitive deficits in children with DMD. So, if a case kind of sounds like DMD and includes mention of some “memory problems or trouble in school” pick DMD.
MNEMONIC: C’mon. Have you ever seen a picture of a female patient doing the Gower maneuver? NO! So of course this is an X-linked disease. Now imagine a child doing the maneuver while wearing a tuX.
MNEMONIC VIDEO: Imagine this kid doing the Gower maneuver in a tuX: www.pbrlinks.com/DUCHENNE1
(DOUBLE TAKE) GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY (G6PD DEFICIENCY)
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD Deficiency) is an X-linked recessive disorder (so look for a male patient!) resulting in jaundice, dark urine, and anemia due to hemolysis from oxidative injury. In newborns, this can present with jaundice in a MALE baby within the first 24 HOURS of life. In other children, it can result in hemolysis after ingestion of fava beans, malaria medications, trimethoprim-sulfamethoxazole, ciprofloxacin, or nitrofurantoin. Look for HEINZ BODIES (purple granules noted in the red cells on microscopy). G6PD Deficiency is associated with patients of African American and Mediterranean descent.
PEARL: Do not test for the deficiency during the acute hemolytic phase. Instead, wait a few weeks because a false negative result can occur due to the build-up of G6PD in reticulocytes.
MNEMONIC: Imagine a bottle of HEINZ BODIES ketchup that has an X located on the exact spot that you have to hit it to make the broken RBCs come out of the bottle. Or, look at this X-shaped HEINZ BODIES bottle of ketchup.
NAME ALERT: This is not the same as glucose-6-phosphatase deficiency, which can affect glucose metabolism and is associated with glycogen storage disease 1, von Gierke’s disease.