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To remember Farber disease, think Far-brrr…🥶 Things that happen when you're cold: 1. Goosebumps → nodules 2. Too cold to move → stiff joints, muscle weakness 3. Shivering → seizures 4. Chattering teeth → weak, hoarse cry 5. Turn off the AC → Acid Ceramidase (AC) defic'y

Temple (mat UPD14) vs Prader-Willi (mat UPD15) Both imprinting disorders have hypotonia→obesity, mild ID, short stature, & pubertal differences ⏰Temple: EARLY puberty ⏰PWS: DELAYED puberty Remember: "arrive EARLY to pray at the Temple" 🏛️ (early puberty in Temple) #GeneChat

Griscelli syndrome ⚪️ Grey hair ("gris" is Spanish for "grey") 🧠 Intellectual disability 🧠 Seizures 🦠Cells (immune deficiency) #GeneChat

Also, the difference between X-linked hypophosphatemia and hypophosphatasia is illustrated in the chart below.

Hypophosphatasia = 'hypo' (low) + alkaline 'phosphatase' (ALP) ALP degrades 3 phos-containing molecules that are ↑ in hypophosphatasia 1. Pyridoxal 5' phos (PLP) → serum biomarker 2. Phosphoethanolamine → urine biomarker 3. Inorganic phos (PPi) → inhibits bone mineralization

Excited to announce the StudyRare Podcast! This will serve as an audio version of the StudyRare newsletter & will include additional content for genetics trainees. In this episode, we highlight sessions from Day 1 @ #ACMGMtg25 View our post here: studyrare.substack.com/p/episode-2-ac…

In Klippel-Feil, the cervical vertebrae "fail" to separate and remain fused. This causes a short neck with limited mobility. Patient may also have kidney anomalies. The letters "ppe" in "Klippel" look like 3 vertebrae stacked together. #GeneChat

📢 We are excited to announce that registration is open for our Bootcamp to prepare for the American Board of Medical Genetics and Genomics (ABMGG) exam! For more info & to register, please visit our website: studyrare.com/abmgg-bootcamp Please feel free to reach out with questions!

HHH syndrome (Hyperornithinemia-Hyperammonemia-Homocitrullinuria) Defective ornithine transport into mitochondria→ hyperornithinemia → urea cycle blocked → hyperammonemia Excess carbamoyl phos reacts w/ lysine (instead of ornithine) & forms homocitrulline (homocitrullinuria)

For more details, have a look at these references: Single large-scale mitochondrial DNA deletion syndromes: ncbi.nlm.nih.gov/books/NBK1203/ Mitochondrial DNA maintenance defects (resulting in mtDNA deletion and depletion) ncbi.nlm.nih.gov/books/NBK48739…

Single vs multiple mtDNA deletions & depletion Single mtDNA deletion (Pearson / Kearns-Sayre / CPEO) → due to sporadic, de novo, 4.9kb deletion Multiple mtDNA deletions & depletion (e.g. POLG-related, AR) → due to errors in mtDNA replication machinery #GeneChat

Lysinuric protein intolerance is due to deficient transport of dibasic amino acids (Orn, Lys, Arg). The disease's name reflects the labs & symptoms: *Lysinuria* is ↑ lysine in the urine *Protein intolerance* is due to urea cycle dysfunction (b/c of ↓ ornithine and arginine).

In mucolipidosis II/III, lysosomal hydrolases can't be tagged with M6P. Thus, lysosomal hydrolases are misdelivered to the extracellular space instead of the lysosome. ↓ hydrolases in lysosome → ↑ large, undigested molecules in lysosome → lysosomal storage disease

M6P is like a GPS for lysosomal hydrolases. It guides enzymes tagged with M6P in the Golgi to the lysosome. Enzyme replacement therapies for lysosomal storage disorders take advantage of this system by tagging recombinant enzymes with M6P so they reach the lysosome. #GeneChat

Use this face to remember the 4 stages of incontinentia pigmenti🌀 1️⃣ Blisters @ birth (eyes👀 look like "B") 2️⃣ Wart-like rash (mustache shaped like "W") 3️⃣ Swirling hyperpigmentation (mustache curls) 4️⃣ Linear hypopigmentation (line-shaped mouth) #GeneChat

What is the difference between arylsulfatase A & B? Both break down sulfates in lysosomes. Their absence affects different organs & substrates: 🔹 ARSA → A = Ataxia 🧠 (Metachromatic Leukodystrophy) → ↑Sulfatide 🔹 ARSB → B = Bones 🦴 (MPS 6) → ↑Dermatan sulfate #GeneChat

Enzyme names in GSD types 3-5 Think of a tree being 'debranched' with a chainsaw 🪚GSD3 = Debranching enzyme. The chainsaw's teeth are shaped like a '3' 🌳GSD4 = Branching enzyme (tree branches) 💪GSD5 = Myophosphorylase. "Myo" = muscle (arms and legs 💪🦵) #GeneChat #Glycogen

🌟Stargardt disease 🌟 1️⃣ Childhood onset 🧒 2️⃣ Vision loss ☁️ 3️⃣ ABCA4 variants 🧬 4️⃣ Avoid excess Vitamin A 🥕🚫 Think 'Stargazer' 🌟🔭to remember these features #GeneChat #Ophthalmology #MedEd

📝 The latest edition of the StudyRare newsletter is now available! This post discusses a case of familial Beckwith-Wiedemann syndrome. Read the full post and sign up for our monthly newsletter with boards-style questions here: studyrare.substack.com #GeneChat

GAMT (Guanidinoacetate methyltransferase) is the enzyme that makes creatine. Patients with GAMT deficiency benefit from creatine supplementation. Creatine is also used by athletes as a supplement🏃🏋🏻 Think: You "Gain Muscle Tone" (GAMT) with creatine 💪 #GeneChat