2025 – PAGE 261 – GENETICS & INHERITED DISEASES

(DOUBLE TAKE) HEMOPHILIA A AND HEMOPHILIA B (AKA FACTOR VIII AND FACTOR IX DEFICIENCY)

Hemophilia A and B refer to factor VIII and factor IX deficiencies, respectively. For both hemophilias, the PTT is increased. Since this is a factor deficiency, look for deep bleeds (muscles, joints, etc.).

MNEMONIC: Have you ever encountered a female hemophiliac? Hmm. You could also imagine the X as a pair of sharp blades going through blood vessels, causing bleeding. That could remind you that hemophiliacs have an X-linked disorder.

HUNTER SYNDROME

For more information on Hunter syndrome, see the Inborn Errors of Metabolism section.

MNEMONIC: X marks the spot! Imagine a HUNTER taking aim at a target with an X! What do you think he’s wearing as he practices his skills? A tuX!

ARGININE VASOPRESSIN RESISTANCE (AKA NEPHROGENIC DIABETES INSIPIDUS)

Arginine vasopressin resistance is a Foxa1 transcription factor deficiency leading to polyuria from a lack of ADH sensitivity. See Fluids & Electrolytes section.

ORNITHINE TRANSCARBAMYLASE

Ornithine transcarbamylase is the most common urea cycle defect and the only one that is X-linked. See the IEM section.

MNEMONIC: ornithine transcarbamylaX

ANDROGEN INSENSITIVITY SYNDROME (AKA TESTICULAR FEMINIZATION)

Testicular feminization (AKA androgen insensitivity) results from an androgen receptor deficiency. See the Endocrinology section.

MNEMONICS: teXticular feminization. Also, when you see “testicular,” that should remind you that the patient has testicles and has an XY genotype, and the patient is a “male” with an X-linked disorder.

(DOUBLE TAKE) WISKOTT-ALDRICH SYNDROME

For Wiskott-Aldrich syndrome, look for a patient with a history consistent with the triad of SMALL Thrombocytes, frequent Infections, and Eczema. Platelets can be small in size and/or number. This is an X-linked disorder, so it will only be found in MALES. Patients develop both T and B cell problems as they age. IgM is usually LOW, while IgA may be HIGH. A history may include findings such as petechiae, bloody diarrhea, bloody circumcision, eczema, and/or otitis media. There is an increased risk of lymphoma in the third decade of life. A BMT is curative.

• MNEMONIC: Wiskott Aldrich = wiXotT ostrich = Imagine a WISe OSTRICH wearing some nerdy black glasses, a tux, and a TIE with the word “T-I-E” spelled down the front.
• MNEMONIC: (image)

• • KEY: X-linked, small T = Represents small platelets (low MPV) and Thrombocytopenia, I = Infections, E = Eczema, Mirrored W = M and arrows show that IgM is low, Duplicate A refers to IgA, and arrows show that IgA levels are increased.
• PEARL: In Idiopathic Thrombocytopenic Purpura (ITP), platelets are BIGGER.
• PEARL: Universal newborn screening for SCID is done in all states.