Named Disorders Flashcards
Friederich Ataxia
(AR) GAA repeats on Chr9 –> frataxin mutation; defective Fe binding protein in mitochondria. This damages dorsal columns (proprioception and vibration sense) as well as spinocerebellar tracts (ataxia, frequent falling). Also see kyphoscoliosis and pes cavus; risk of death from HCM; presents in adolescence (ages 5-15).
Charcot-Marie-Tooth disease
(AD) Progressive hereditary neurodegenerative disorders due to defective production of the structure and function proteins of the peripheral nerves/myelin sheath. Presents as sensory and motor loss, as well as kyphoscoliosis and pes cavus, around age 30-40.
Metachromatic Leukodystrophy
(AR) Lysosomal storage disorder due to arylsulfatase A deficiency and cerebroside sulfate accumulates, which impairs myelin sheath production (“leuko”- white dystrophy).
Get central and peripheral demyelination with ataxia around age 9-12mo, dementia, developmental delay, muscle weakness, atrophy, MRI showing demyelination.
Isolated Atrial Amyloidosis (IAA)
form of senile amyloidosis (associated with aging) where ANP is misfolded and deposited in the cardiac atria; increases the risk of afib
Actinic keratosis
Premalignant skin lesions that are rough with sandpaper like texture, “felt more than seen”, and start out as small/flat then become elevated and maybe even form horns (hyperkeratosis).
Caused by UV damage, therefore seen in people who worked outside a long time. Can progress to SCC (
Acyl-CoA Dehydrogenase deficiency
The most common deficiency resulting in impaired FA oxidation; the missing enzyme is the one that starts FA oxidation (once the acyl-CoA has been transported into the mitochondrion by carnitine). Clinical = fasting child with vomiting and lethargy, maybe a seizure, and hypoglycemia and NO KETONES (no acetoacetate - hypoketotic hypoglycemia).
Differentiate from GSD because there will be no ketones here.
Differentiate from primary carnitine deficiency because that will also have muscle weakness, cardiomyopathy, and elevated TGs in addition to hypoketotic hypoglycemia.
CGD
lack of NADPH oxidase means impaired NT respiratory burst and thus inc vulnerability to catalase positive bugs -
Especially Serratia, S. aureus, Burkholderia cepacia, Aspergillus, and Nocardia
Homocystinuria
Methionine cycle = Met –> SAM –> SAH –> Homocysteine; Hom –> Met, OR Hom –> Cystathione –> Cysteine
If you can’t convert Homo–> cysteine (MC 2/2 deficiency of cystathione synthase) then homocysteine accum, which makes for a hypercoagulable state, can cause acute coronary syndrome (like 12yo with angina, or CVA), can also result in ectopia lentis, ID, and long slender fingers.
This would make cysteine an essential aa for these people because they can’t make it from homocysteine. Can also supplement B6 because even when the enzyme is deficient, 50% of patients respond to supplemental pyridoxine. Should also reduce dietary methionine.
Hunter’s syndrome
deficiency of iduronate sulfatase; heparan sulfate and dermatan sulfate accumulate; similar to Hurler’s (gargolyism) except - no corneal clouding, and very aggressive
Hurler’s syndrome
deficiency of alpha-L-iuduronidase; heparan sulfate and dermatan sulfate accumulate; developmental delay, loss of milestones (develop normally for a while, then they regress), gargoylism = dwarfism, distinct facial features (frontal bossing, hypertelorism, widened nasal bridge, gapped teeth, gingival hyperplasia, and thickened tongue), cloudy corneas, HSM, airway obstruction (from thickened tongue, leads to death)
Hyperplastic arteriolosclerosis
when a patient has persistent diastolic HTN (>130), the arterioles get onion-like concentric thickening of the walls; this can lead to sustained HTN, kidney damage (oliguria), increased RAAS activity (vicious cycle), and potentially cranial sx like Has, papilledema, HTNive encephalopathy, and retinal hemorrhage/exudate
Kallman syndrome
delayed puberty + anosmia
2/2 defective migration of GnRH cells into hypothalamus, so there’s no secretion of GnRH from hypothalamus
Klinefelter syndrome
47,XXY male - primary hypogonadism, tall, gynecomastia, learning/social difficulties; dec. testosterone from damaged Leydig cells, inc. FSH/LH (no feedback; sclerosed seminiferous tubules), and inc. estradiol
Clinical hallmark is the hypogonadism - small firm testes; lack of 2ndary sex development - despite being tall
Krabbe’s Disease
deficiency of galactocerebrosidase; galactocerebide accumulates; CNS symptoms like delayed development, optic atrophy (blindness), Globoid cells (multi-nuc MPs); “4mo old with seizures, irritability, vomiting, developmental delay, inability to track(blind)…”; differentiate from Fabry’s by optic atrophy
Marfan vs. Ehlers-Danlos: mutation and clinical picture
Marfan = mutated fibrillin, all elastin all the time; person is really tall with long limbs, sunken chest; but doesn’t affect cartilage like joints
EDS = defective collagen synthesis (often lysyl hydroxylase or procollagen peptidase) to where the person has hypermobile joints, stretchy skin, and fragile tissue vulnerable to bruising
MEN1, MEN2a, MEN2b
MEN 1: pituitary, parathyroid, pancreas
MEN 2A: parathyroid, pheo’s; medullary thyroid
MEN 2B: oral/GI neuroma, pheo’s; medullary thyroid
Necrolytic migratory erythema
an elevated painful and pruritic rash affecting the face, groin, and extremities, the papules/plaques coalesce to form large lesions with bronze indurations; features in glucagonoma, which will also see high glucagon and which may present as new onset DM, +/- anemia of chronic disease
Niemann-Pick Disease
deficiency of sphingomyelinase; sphingomyelin accumulates; tetrad of neuro probs/neurodegeneration, HSM, foam cells (fatty accumulation of sphingomyelin in MPs), cherry red macula
Ornithine Transcarbamylase deficiency
Urea cycle: carbamoyl phosphate + ornithine –> citrulline
Deficiency = accum. carbamoyl phosphate, gets pushed into the pyrimidine synthesis pathway but then gets stuck at orotic acid
Findings: orotic acidemia/aciduria and hyperammonemia (a metabolic emergency - manifests as AMS/unresponsive and tachypnea); triggered by illness or excessive protein intake
*Differentiate from orotic aciduria alone: no megaloblastic anemia in OTC deficiency
Primary carnitine deficiency
without sufficient carnitine (mitochondrial membrane transport protein for FAs), FA can’t be transported into the mitochondria; they won’t be oxidized and no acetyl-CoA will be produced for either TCA or ketone bodies
Sarcoidosis
histo: non-caseating granulomas with epithelioid cells; CXR = bilateral hilar lymphadenopathy; typically a young black woman with non-specific sx like fever/malaise/wt loss; +/- skin involvement ranging from macules to painful shin nodules (erythema nodosum)
Small Cell Lung Cancer
neoplasm of primitive cells from basal layer of bronchial epithelium; can have varying degrees of neuroendocrine differentiation, as such they may stain for chromogranin/synaptophysin/NCAM-1 (aka CD56)/neuron-specific enolase, and/or they may express neurofilaments and contain secretory granules; look like LCs but typically larger, arrange in sheets or clusters
This is the cancer associated with all the syndromes: Cushing’s, PTHrP, SIADH, Eaton-Lambert
Tay-Sachs Disease
deficiency of hexosaminidase A (Tay-Six dz); GM2 ganglioside accumulates; neurological problems (CNS/peripheral), cherry red macula, NO HSM everrrrrr, onion skin lysosomes
Lynch syndrome - associated cancers
colorectal; endometrial; ovarian
–> from MSH mutation
CREST Syndrome
A type of limited scleroderma (limited meaning it doesn’t include viscera)
Anti-centromere antibodies are specific for limited scleroderma whereas anti-topo I are specific for diffuse scleroderma (aka systemic sclerosis)
C = calcinosis R = Raynaud's E = Esophageal dysmotility (like GERD or dysphagia) S = sclerodactyly (begins as non-pitting edema, then becomes thickened, ulcerated skin of hands/feet) T = telangiectasias
Androgenetic alopecia
aka male-pattern baldness
these people have higher levels of 5-alpha-reductase (turns testosterone into DHT) and a higher quantity of androgen receptors.
Finasteride (a 5-a-reductase inhibitor) will reverse androgenetic alopecia.
Turner syndrome
46,X
Loss of paternal X chromosome
Results in webbed neck/cystic hygromas, broad chest with wide nipples, streak/atrophic ovaries, short stature, horseshoe kidney, bicuspid aortic valve, coarctation of the aorta (diminished LE pulses), low set ears, low hairline, lymphedema (swelling of bilateral extremities), and overall short stature
Congenital torticollis
A contracture of the SCM caused by fetal malpositioning in utero, or traumatic delivery (breech).
This causes injury and fibrosis to the SCM, resulting in a fetal head position that is away from the side of injury.
Typically presents clinically by 2-4wks of age.
Triad of Wiskott Aldrich syndrome (and the rest of the disease)
Triad = thrombocytopenia, recurrent infections, eczema
Disease is an X-linked deficiency of both B and T cells
Tx is bone marrow transplant
WASP = the defective protein, which results in T cells not being able to polarize and therefore can’t make the immunologic synapse, can’t activate B cells; also plays role in the small platelets (removed by the spleen hence thrombocytopenia)
Alkaptonuria
AR deficiency of homogentisic acid dioxygenase; get accumulation of homogentisic acid (on its way to fumarate for TCA cycle). Relatively benign in childhood, then severe arthritis in adult life with pigment deposition in cartilage (blue-back spots in sclera and ear); the deposits are also in joints which causes ankylosis, restricted movement, and pain
+pee that turns black overnight
Hirschsprung’s disease
Failure of neural crest cells to migrate down to form the submucosal (Meissner’s) and myenteric (Auerbach) plexus; always involves the rectum because that would be the farthest sites to migrate to.
Dx with submucosal biopsy of the narrowed portion of the bowel (because the dilated part proximal to that is where everything is getting stuck, that’s why it’s big).
Lead poisoning
Child or someone who works in industry -
abdominal pain, weakness, constipation, and in severe cases neuro sx (causing HA, cognitive sx, peripheral neuropathy)
Blood smear: basophilic stippling on background of hypochromic, microcytic anemia
vs. Acute porphyria - episodes of abdominal pain without tenderness, and no anemia
Arginase deficiency
In urea cycle*
Normally: converts Arginine + H2O –> Ornithine + Urea
Without it: build up of Arginine in blood, spastic diplegia, and growth delay (“3yo boy with progressive bilateral leg stiffness and abnormal involuntary movements with delayed cognitive development”)
Differentiator is nearly no hyperammonemia at all
*The only urea cycle enzyme deficiency that is XLR
Fanconi anemia
Inherited disorder of bone marrow causing aplastic anemia.
The patient will also be short and thumbs are absent.
Increased risk of malignancy like MDS and AML.
Polyarteritis nodosa
medium-vessel vasculitis
- usually idiopathic; associated with HbsAg
- renal, skeletal, neuro, and visceral (GI) vessels (NOT lung); episodes of system symptoms due to ischemia
- string of pearls on imaging from: transmural inflammation of vessel wall with fibrinoid/eosinophilic necrosis
- immune complex mediated, especially when associated with HepBsAg (30% of cases)
