Clinical Correlates Flashcards
(155 cards)
1
Q
Congenital Hypertrophic Plyoric Stenosis
A
- Pyloric canal lumen narrowing due to pyloric muscle hypertrophy
- Clinical Presentation: Vomiting (not bile stained), presents ~3weeks-5months
- Physical Exam: Pyloric mass (olive-shaped), peristaltic waves
- Imaging: Barium Swallow shows defect in pyloric sphincter filling
- Ultrasound: Thickening of pyloric sphincter
2
Q
Duodenal Stenosis
A
- Partial lumen occlusion due to incomplete recanalization
- Clinical presentation: Vomiting (bile stained if stenosis is distal to bile duct opening)
3
Q
Duodenal Atresia
A
- Complete lumen occlusion due to incomplete recanalization
- Clinical presentation: Polyhydramnios, Vomiting beggining immediately after birth
- Imaging: Double Bubble sign - 1 air bubble in Stomach & 1 air bubble in Proximal Duodenum
4
Q
Annular Pancreas
A
- Causes Duodenal obstruction
- Due to bifid ventral pancreatic bud
5
Q
Abnormalities of Midgut Rotation
A
- Non-rotation: Small intestine lies right (instead of left), Asymptomatic
- Reversed rotation: Clockwise rotation (instead of Counterclockwise), Duodenum lies anterior (instead of posterior) to Transverse Colon, SMA compressing Transverse Colon
- Subhepatic Cecum & Appendix: Cecum adhered to Liver & doesn’t descend into Iliac Fossa
- Mixed Rotation & Volvulus: Cecum lies inferior to Pylorus & fixed to posterior abdominal wall, May cause Duodenal Obstruction
6
Q
Non-Rotation of Midgut Abnormality
A
- Caudal Limb returns 1st (instead of Cranial end)
- Small Intestine lies right (instead of left)
- Generally asymptomatic
7
Q
Reversed Rotation of Midgut Abnormality
A
- Midgut loop rotates clockwise (instead of counterclockwise)
- Duodenum lies anterior to Transverse Colon (instead of posterior)
- SMA compresses Transverse Colon
8
Q
Sub-hepatic Cecum & Appendix of Midgut Abnormality
A
- Cecum adhered to Liver & doesn’t descend into Iliac Fossa
- May cause difficulty in Appendicitis diagnosis
9
Q
Mixed Rotation & Volvulus of Midgut Abnormality
A
- Cecum lies inferior to Pylorus & is fixed to posterior abdominal wall
- May cause Duodenal obstruction
10
Q
Omphalocele
A
- Embryological defect
- Due to persistance of abdominal herniation covered by fetal membranes
11
Q
Umbilical Hernia
A
- Embryological defect
- Due to incomplete closure of Umbilical Ring
- Not covered by fetal membrane
- May contain Omentum & small portions of Small Intestines
- Clinical presentation: Soft swelling covered by skin, protudes during cry/cough/strain, easily reduced through fibrous ring at umbilicus
12
Q
Gastroschisis
A
- Due to incomplete closure of lateral folds during 4th week of development (defect near median plane of abdominal wall)
- Clinical presentation: Viscera protrudes into amniotic cavity
13
Q
Meckel’s Diverticulum
A
- Finger-like projection from Ileum
- Due to retention of Omphaloenteric Duct
- Clinical presentation: “Rule of 2s” - 2 problems (Appendicitis & Peptic Ulcer), 2 secretory tissues (Gastric & Pancreatic), 2 inches long, 2 feet proximal to Ileocecal Junction, 2x more likely in males than females, 2% of population
- Features: Periumbilical pain & internal bleeding
14
Q
Umbilical Fistula
A
- Due to patent Omphaloenteric Duct
- Forms communication between Umbilicus & Intestinal Tract
- Clinical presentation: Fecal discharge at Umbilicus, infection at Umbilical Stump
15
Q
Low Anorectal Malformation
A
- Rectum ends inferior to Puborectalis Muscle
- Clinical features: No anal opening, abnormal opening into Perineum, Anal dimple/stenoitic opening, Anus buldge
- Examples: Anal Stenosis, Membranous Atresia, Imperforate Anus
16
Q
High Anorectal Malformation
A
- Rectum ends superior to Puborectalis Muscle
- Clinical features: Present as Fistulas that communicate with Urogenital system, flat Perineum, No pigmentation or Anal dimple, Males: Rectourethral/Rectovesical/Rectoprostatic, Females: Rectovestibular/Rectovaginal
- Examples: Anorectal Agenesis with Fistula, Rectal Atresia
17
Q
Anorectal Agenesis with Fistula
A
- High Anorectal Anomaly
- Due to incomplete separation of Cloaca from Urogenital Sinus by Urorectal Septum
- Clinical features: Rectum ends blindly & Fistula, Anal Pit
- Types: Rectovesicular - Fistula from Rectum to Bladder; Rectourethral - Fistula from Rectum to Urethra; Rectovaginal - Fistula from Rectum to Vagina; Rectovesibular - Fistula from Rectum to Vaginal Vestibule
18
Q
Rectal Atresia
A
- High Anorectal Anomaly
- Due to recanalization of Colon or from defective blood supply
- Clinical features: Anal Canal & Rectal Septum are both present but separated, intestinal segments connected by fibrous cord (remnant of atretic rectum)
19
Q
Anal Stenosis
A
- Low Anorectal Anomaly
- Due to dorsal deviation of Urorectal Septum as it grows caudally
- Clinical featuers: Narrowed Anal Canal
20
Q
Membranous Atresia
A
- Low Anorectal Anomaly
- Due to failure of Epithelial Bulge to perorate (at 8th week) - Persistant Anal Membrane
- Clinical features: Anal Pit, thin layer of tissue separates Anal Canal from External environment, Epithelial Anal Plug remnant budges on straining & appears blue (due to superior Meconium)
21
Q
Imperforate Anus
A
- Low Anorectal Anomaly
- Clinical features: Anal pit, Ectopic Anus/Anal Canal ends blindly/Anoperineal Fistula/Anovaginal Fistula/Anourtheral Fistula
22
Q
Hirschspring Disease/Congenital Megacolon
A
- Due to failure of Neural Crest Cell migration (during weeks 5-7)
- Clinical features: Dilated proximal Large Intestine, Aganglionic narrow segment with no Peristalsis
- Cause of Neonatal Intestinal Obstruction
23
Q
Wernicke-Korsakoff Syndrome
A
- Thiamine/Vit B1 deficiency causing low PDH activity (Pyruvate —> Acetyl Co-A)
- Clinical features: Ataxia, Ophthalmoplegia, Memory loss, Cerebral hemorrhage, Confabulation (false memories)
- At risk patients: Alocoholics & malnourished
24
Q
Beriberi Disease
A
- Thiamine/Vit B1 deficiency causing low PDH activity (Pytuvate —> Acetyl Co-A)
- Wet type clinical features: Heart failure, decreased ATP, increased CO, dilated Cardiomyopathy
- Dry type clinical features: Systemic muscle wasting, Polyneuritis
25
Pyruvate Dehydrogenase (PDH) Deficiency
- Metabolic Effect: Increased blood Pyruvate, Alanine, & Lactic Acid, Decreased Acetyl Co-A & ATP production
Clinical features: Lactic Acidosis, Neurologic defects, Myopathy, fatal at early age
- Presenting facial features: Frontal prominence, wide nasal bridge, flared nares, long philtrum, brain malformations (Corpus callosum agenesis, cerebral & basal ganglia cysts)
- Therapies: Dicholoracetate; Supplementation with Thiamine, Lipoic Acid, & Carnitine; High fat, low carb diet
26
Heavy Metal Poisoning
- Lipoid Acid binds to heavy metals & inactivates PDH Complex
27
Perforation of Peptic Ulcer of Stomach along Posterior Wall
Blood collects in Lesser Sac which can then communicate with Greater Sac via Omental/Epiploic Foramen of Winslow
28
Pringle Maneuver
- Compression of Hepatoduodenal Ligament
| - Prevents blood flow into Liver
29
Leber’s Hereditary Optic Neuropathy
- Defect in Complex 1
- Characterization: Degeneration of Retinal Ganglion cells, Atrophy of Optic nerve, usually begins around 25-35, leads to legal blindness
30
Deafness Induced by Aminoglycoside Antibiotics
- Caused by Mitochondrial rRNA
- Characterization: Moderate to porfound hearing loss Hearing loss occurs within days to weeks after aminoglycoside administration, mutation may cause predisposition to aminoglycoside toxicity
31
Mitochondrial Myopathies
- Muscle Disease
| - Includes: Kearns-Sayre Syndrome, MELAS, MERRF
32
Kearns-Sayre Syndrome
- mtDNA deletion
- Characterization: Onset before 20 years old, eye muscle paralysis, Retina degradation, CHF, muscle weakness, Ataxia, Diabetes, Dementia, Mental illness, Progressive External Ophthalmoplegia
33
MELAS Syndrome
- Mitochondria myopathy, Encephalopathy, Lactic Acidosis, Stroke-like episodes
- Due to mutation in mitochondrial tRNA
- Clinial features: Strokes, myopathy, muscle twitching, dementia, deafness
- Characterization: Occurs with 1st stroke-like episode at 14-15 years old, Lactic Acid accumulates in blood & is toxic to brain
34
MERRF Syndrome
- Myoclonic Epilepsy, Ragged Red Fibers
- Mutation in mitochondrial tRNA
- Characterization: Onset around 6-16 years old
- Clinical features: Myoclonus (1st symptom), seizures, muscle weakness, worsening eyesight, hearing loss
35
Perforated Peptic Ulcer
- Clinical Presentation: Sudden & severe abdominal pain, abdominal rigidity (peritoneal irritation), “free air” under Diaphragm/Pneumoperitoneum, excessive bleeding (maybe)
36
Peptic Ulcers
- Most common location: Duodenal Bulb (1st part)
- Secondary site: Stomach lesser curvature
- Artery invasion: Gastroduodenal Artery or branches of Posterior Superior Pancreaticoduodenal Artery
37
Posterior Perforation of Stomach
Contents spill into Lesser Sac/Omental Bursa
38
Anterior Perforation of Stomach
Contents spill into Greater Sac
39
Small Bowel Obstruction
- Usually centrally located
- Imaging: “Stacks of coins” - Plica Semilunaris (lines continuous from luminal wall to luminal wall)
- Clinical features: Increased intra-luminal gas, nausa/vomiting, abdominal distention, increased bowl sounds on physical exam, no passage of gas per Rectum
- Characterization: Obstruction causes proximal tube dilation & distal tube flattening
40
Large Bowel Obstruction
- Located in Periphery
- Imaging: Presence of Haustra
- Clinical features: Increased intra-luminal gas, nausa/vomiting, abdominal didstension, increased bowel sounds on physical exam, obstipation (no gas passager per rectum)
41
Portal Hypertension
PortoCaval Anastomoses between Superior, Middle, & Inferior Rectal Veins becomes Varicosed
42
Hematochezia
- Passage of fresh blood per Anus, usually in/with Stools
| - Due to Portal Hypertension
43
Diverticulosis
- Colonic mucosa/submucosa hernitation through muscle
- Location: Sigmoid Colon (generally)
- Radiology: Diverticulum seen of Barium Enema & Colonoscopy
- Labs: Anemia or positive stool Guaiac Test
- Clinical features: Left lower abdominal pain, abdominal tenderness & distention, fever, painless rectal bleed
- Complications: May lead to Diverticulitis (infection) & Peritonitis/Fistula (rupture)
44
Sigmoid Volvulus
- Colon obstruction due to Sigmoid Colon twisting around Mesentery
- Radiology: Double loop obstruction, “coffee bean” sign, no gas seen in rectum
- Clinical features: Abdominal pain, nausea/vomiting, constipation, small/large bowl obstruction symptoms
- Complications: Colonic Ischemia, Colonic Perforation, Peritonitis
45
MODY-2
- Maturity Onset Diabetes of the Young, Type 2
- Characterization: Impaired Insulin secretion from pancreatic B-cells, Glucokinase deficiency
- Clinical features: Chronic mild fasting Hyperglycemia without overweight/metabolic syndrome
46
Liver Cirrhosis
- Progressive destruction of Hepatocytes & replacement by fibrous tissue
- Blood flow disruption & decreased hepatocyte function
- Causes: Fatty Liver Disease, Toxins, Infections
- Appearance: Nodular - due to fibrosis
- Clinical features: Firmness (due to fibrous tissue), impeding blood circulation
- May lead to Portal Hypertension
47
Pringle Maneuver
- Clamping of the Hepatoduodenal Ligament of the Liver to prevent bleeding from the Proper Hepatic Artery
48
Gallstones
- Common in fat, fertile, female of 40
- May be asymptomatic
- May produce Colic (SM spasm to expel stones) or Acute Cholecystitis (subdiaphragmatic parietal peritoneum irritation by Phrenic Nerve, right upper quadrant pain)
- Jaundice (biliary tree obstruction & backup of bile)
- Location: Ampulla (pancreatitis), Hepatic Duct (No bile), Cystic Duct (bile, acute cholecystitis), Major Duodenal Papilla (bile, jaundice, acute cholecystitis, acute pancreatitis)
49
Portal Hypertension
- Hepatic Portal Vein obstruction
- Portocaval Shunt: Reduces Portal Hypertension by diverting blood from Portal Venous System to the Systemic Venous System through creating a shunt between the Portal Vein & IVC/Splenic Vein & Left Renal Vein
50
Von Dierke Disease
- Type I Glycogen Storage Disease
- Enzyme Deficiency: G6Pase
- High Glycogen levels with normal structure
- Clinical Features: Hepatomegaly, Progressive Renal Disease, Severe fasting Hypoglycemia (no glucose increase with Glucagon/Epi), Lactic Acidosis, Hyperuricemia, Hyperlipidemia, Failure to Thrive
- Treatment: Avoid fasting, nocturnal nasogastric glucose infusions or uncooked cornstarch in water
51
Pompe Disease
- Type II Glycogen Storage Disease
- Enzyme Deficiency: Lysosomal Alpha 1, 4 Glucosidase (Acid Maltase)
- High Glycogen levels with normal structure, & normal Glucose levels
- Classification: GSD, LSD, MD
- Clinical features: Cardiomegaly, Hepatomegaly, Myopathy, Hypotonia, Neuromuscular disorder, Elevated CK-MM
- Treatment: Enzyme replacement therapy by infusion
52
Cori Disease/Forbes Disease/Limit Dextrinosis
- Type III Glycogen Storage Disease
- Enzyme Deficiency: Debranching Enzyme/4:4 Transferase
- Classification: GSD & MD
- Abnormal Glycogen structure with short outer branches
- Clinical features: Hypotonia, Carbdiomyopathy, Hepatomegaly, Mild Hypoglycemia
53
Andersen Disease
- Type IV Glycogen Storage Disease - Familial Cirrhosis
- Enzyme Deficiency: Branching Enzyme/4:6 Transferase
- Abnormal Glycogen structure: long Glucose chains & less branches
- Clinical features: Hepatomegaly, Infantile Cirrhosis, Early dealth in childhood, Hypotonia, Cardiomyopathy
54
McArdle Disease
- Type V Glycogen Storage Disease
- Enzyme Deficiency: Myophosphorylase Isozyme
- High Glycogen levels with normal structure & normal hepatic Isozyme
- Clinical features: Weakness & Cramping after exercise, Myoglobinemia, Myoglobinuria
- Diagnosis: Muscle Weakness Test - lower Lactate levels after exercise since Glycogen degradation is reduced & less Lactate formed
55
Hers Disease
- Type VI Glycogen Storage Disease
- Enzyme Deficiency: Hepatophosphorylase Isozyme
- High Glycogen levels with normal structure, & normal Isozyme
- Clinical features: Hepatomegaly, Growth retardation, Mild fasting Hypoglycemia
56
Tarui Disease
- Type VII Glycogen Storage Disease
- Enzyme Deficiency: PFK-1 M-subunit (Muscle, RBCs)
- Normal Isozyme
- Clinical features: Muscle cramping (Similar to McArdle Disease), Hemolysis
57
Benign/Essential Fructosuria
- Deficiency: Liver Fructokinase
- Accumulates: Fructose not metabolized & excreted in urine; No toxic accumulates
- Clinical features: Asymptomatic
- Urinalysis: Abnormal - Reducing sugar (not Glucose or Galactose)
58
Hereditary Fructose Intolerance
- Deficiency: Aldolase B
- Accumulates: Fructose 1-P
- Diagnosis: Hypoglycemia folloiwng dietary fructose/sucrose, reducing sugar in urine, enzyme assays
- Urinalysis: Abnormal - Reducing sugar (not Glucose)
- Clinical features: Hypoglycemia (drowsy & apathetic) following trigger (sucrose or fructose), Hepatocellular failure, Jaundice, No Cataracts
- Treatment: Avoid dietary fructose (fruits)
59
Classical Galactosemia
- Deficiency: GALT (Galactose 1-P Uridyl Transferase)
- Accumulates: Galctose & Galactose 1-P
- Diagnosis: Newborn screening heel prick test
- Urinalysis: Abnormal - Reducing sugar (not Glucose)
- Clinical features: Liver Damage, Cataracts, Developmental Delay (Classical Triad), Jaundice, Hepatomegaly, Hypoglycemia, Vomiting after feeds, Failure to thrive, Brain damage
- Treatment: Dietary exclusion of Galactose & Lactose, Soy-milk or Lactose-free milk substitute in place of breast milk, monitor Galactose 1-P levels
60
Non-Classical Galactosemia
- Deficiency: Galactokinase
- Urinalysis: Abnormal - Reducing sugar (not Glucose)
- Clinical features: Cataracts
61
Alcohol Induced Hypoglycemia
- Ethanol-mediated NADH increase in Liver
- Gluconeogenesis intermediates divereted to alternate reaction pathways, resulting in decreased Glucose synthesis
- Clinical features: Lactic Acidosis (Pyruvate —> Lactate), Malate Trapping (Oxaloacetate —> Malate)
- More severe if person hasn’t eaten
62
Conditions that present with Hypoglycemia
- Acute Alcohol Intoxication
- GSDs (Von Gierke - Type I, Cori - Type III, Hers - Type VI
- Hereditary Fructose Intolerance
- Classical Galactosemia
- Liver Fatty Oxidation Defect
- Insulinoma
- Addison Disease
- Congenital Adrenal Hyperplasia (CAH)
- Insulin Overdose
- Sulfonylurea Overdose
63
Peptic Ulcers
- Crater-like lesions due to loss of mucosal protection or increase acid secretion which leads to inflammation & necrosis
- Common causes: H. Pylori Infection (Secretes Urease & Protease to breakdown mucus & create Alkaline env., stimulates Gatrin increasing Acid/Pepsid), Tobacco smoking, NSAIDs (inhibit Prostaglandins), Zollinger Ellison Syndrome (Gastrinoma)
- Complications: Bleeding (erosion of base BVs), Perforation, Peritonitis, Macrocytic Pernicious Anemia
64
Barrett’s Esophagus & Gastroesophageal Reflux Disease (GERD)
- Gastric reflux back into lower esophagus
- Cause: Weakened esophageal sphincter
- Clinical features: Chest pain/burning
- Complications: Metaplasia (simple columnar epithelium) & Dysplasia (adenocarcinoma)
65
Malabsorption Syndrome
- GI Tract Disease resulting in abnormal nutrient absorption
- Causes: Mucosal damage (Celiac Disease, Tropical Sprue, VitB12 Malabsorption), Enzyme Deficiency (Disaccharidase deficiency, Pancreatic insufficiency), Infection, Short Intestine Structure, Chron’s Disease
- Clinical feaures: Weight loss, Steatorrhea, Muscle wasting, Bloating/Flatulence/Diarrhea, Macrocytic Anemia (VitB12 or Folic Acid), Bleeding disorders, Bone pain/Tetany
66
Celiac Disease
- Gluten sensitive enteropathy; Autoimmune mediated Gliadin intolerance
- Inflammation of disal Duodenum & proximal Jejunum
- Histology: Villi atrophy & Crypt hyperplasia, Increased Lymphocytes & Plasma Cells in LP
- Diagnosis: IgA antibodies for Transglutaminase, Endomysium, & Deaminated Gliadin peptide
- Treatment: Gluten free diet
67
Chron’s Disease
- Ulcer formation
- Mainly affecting terminal Ileum of SI but also LI & upper GI
- Histology: Cobblestone appearance - Long fissure-like ulcers with normal mucosa in between & underlying inflammation, Granuloma formation with Giant cells
- Complications: Fistulas, Fibrosis & Obstruction
- Clinical features: Crampy abdominal pain, Malabsorption
68
Appendicitis
- Cause: Block of Cecum opening
| - Clinical features: Scarring, thick mucus & stool
69
Colonic Adenomatous Polyps/Adenomas
- Intraepithelial Neoplasm
- Dysplastic epithelium forms glands or villous processes
- Clinical features: Usually asymptomatic, occult bleeding
- Types: Tubular, Villous, Tubulovillous
70
Congenital Megacolon/Hirschsprung Disease
- Failure of Myenteric Plexus development in distal ailmentary canal
- Clinical features: Functional obstruction (decreased peristaltic movements), Dilated colonic segment proximal to aganglionic region
71
Congestive Heart Failure
- Congestion: Blood backup in liver sinusoids due to decreased output of right side of heart
- Hypoperfusion & Hypoxia: Decreased oxygenated blood to Liver due to decreased blood to/from left side of heart
- Centrilobular Necrosis - in Zone 3 hepatocytes
72
Hepatic Steatosis/Fatty Liver Disease
- Causes: Chronic Alcholism or Metabolic Syndrome (Non-alcoholic fatty liver)
- Appearance: Signet ring of hepatocyte
- Clinical features: Increased intrahepatic lipid droplets, Hepatomegaly
- Progression to Cirrhosis
73
Acute Pancreatitis
- Sudden Pancreas inflammation
- Causes: Gallstones, Alcohol abuse
- Due to pancreatic duct blockage by gallstone, temporary block (& damage) of pancreatic fluid
74
Cystic Fibrosis
- AR
- Mutation in CFTR gene on chromosome 7
- Abnormal epithelium transport of Cl- increases viscocity of exocrine gland secretion
- GI Manifestations: Malabsorption Syndrome secondary to pancreatic dut obstruction, Pancreatitis, Fibrosis, Biliary tree obstruction by Gallstones, Malnutrition
- Treatment: Pancreatic enzyme supplementation
75
Systemic Fatty Acid Oxidation Disorders
- Organs affected: Livder & MUscle
- Includes: MCAD Deficiency, Carnitine Deficiency, CPT-I Deficiency
- Clinical features: Hypoglycemia, Hypoketosis, Metabolic crisis following illness
76
Myopathic Fatty Acid Oxidation Disorders
- Organs affected: Muscle (skeletal & cardiac)
- Includes: Myopathic Carnitine Deficiency, CPT-II Deficiency
- Clinical features: Cramps during Aerobic exercise, Unable to perform Aerobic exercise
- Labs: Elevated blood Lactate following ischemic exercise, Myoglobinuria, elevated serum CK-MM, Lipid droplets/elevated TAG in muscle biopsy
77
MCAD Deficieny
- Classification: Systemic FA Oxidation Disorder
- Presentation: 6-24 months
- Cause: Decreased oxidation of of Medium Chain FAs - Tissues (Liver, Muscle) can’t use FAs for energy, Impaired Gluconeogenesis (less ATP & Acetyl CoA)
- Clinical features: Severe hypoglycemia (metabolic crisis) on fasting or illness, Hypoketoniemia
- Labs: Medium chain acyl carnitines & Dicarboxilic acids in Urine
- Treatment: IV Glucose, frequent feeding (high carb, low fat)
78
Carnitine I Deficiency
- Classification: Systemic FA Oxidation Disorder
- Cause: Impaired Carnitine uptake into tissues, Impaired long-chain FAs into Mitochondria, Decreased Beta Oxidatoin
- Presentation: Early
- Clinical features: Hypoglycemia (impaired Gluconeogenesis) & Hypoketosis
- Affects: Liver isoform
- Treatment: IV Glucose, frequent feeding (high carb, low fat), Carnitine Supplements
79
Carnitine II Deficiency
- Classification: Myopathic FA Oxidation Disorder
- Cause: Impaired Carnitine uptake into tissues, Impaired long-chain FAs into Mitochondria, Decreased Beta Oxidatoin
- Clinical features: Muscle weakness, Cardiomyopathy, Cramps upon aerobic exercise
- Labs: Elevated CK-MM, Myoblobin in Urine, Skeletal msucle damage, Lipids in muscle biopsy
- Affects: Muscle isoform
- Treatment: Cease muscle activity, Glucose & Carnitine supplements
80
Jamaican Vomiting Sickness
- Cause: Eating unripe Ackee fruit (Caribbean & African) which contains Hypoglycin A (MCAD inhibitor)
- Clinical features: Hypoglycemia, Vomitng, Drowsiness, Coma, Death
- Labs: Medium Chain Acyl Carnitines in urine
81
Zellweger Syndrome
- Defective peroxisomal biogenesis (liver & brain)
- Labs: Increased C26 FAs
- Clinical features: Neuro. manifestations, delayed development, extensive demyelination, Hepatomegaly, Hepatocellular failure, fatal in infancy
82
Refsum Disease
- Peroxisomal Phytanyl CoA Alpha-Hydroxylase deficiency - Alpha Oxidation Defect
- Phytanate accumulation
- Clinical features: Visual defects, Ataxia, Polyneuropathy, Skeletal Manifestations
- Treatment: Restrict branched chain FAs (Phytanic Acid)
83
Ketoacidosis in Uncontrolled Diabetes Mellitus
- Uncontrolled DM —> Excessive AT Lipolysis —> HS Lipase very active
- Labs: Ketonemia, Ketonuria, elevated 3-hydroxybutyrate & Acetoacetate in blood & urine
- Clinical features: High anion gap metabolic acidosis, hyperventilation, Fruity breath odor
84
Smith-Lemli-Optiz Syndrome (SLOS)
- Deficiency of 7-Dehydrocholesterol Reductase - 7-DHC buildup & Cholesterol reduction
- Due to loss of function mutations in DHCR7 gene
- Clinical features: Heart defects, limb deformations, growth retardation, microcephaly, mental disability, ambiguous genitalia in males, high infant mortality rate
- Treatment: Cholesterol administration (for help with growth)
85
Cholesterol Gallstone Disease/Cholelithiasis & Biliary Disease
- Precipitation of Cholesterol in bile within Gallbladder
- Due to: Deficiency of Lecithin/Phosphatidylcholine &/or Bile Salts (Glycocholic or Taurochenodeoxycholic Acid)
- Diagnosis: CT or Ultrasound
86
Cholestatic Disease
- Biliary obstruction of Small Bile Ducts or Extrabilliary Ducts
- Clinical features: Steatorrhea, Lipid malabsorption, Jaundice (hyperbilirubinemia)
- Cause: Hepatic dysfunction (decreased bile production), Increased Cholesterol secretion into Bile, Bile Acid malabsorption, Biliary tract obstruction, Enterohepatic circulation interruption
- Treatment: Laparoscopic Cholecystectomy, Bile Acid (Chenodiol/Chenodeoxycholic Acid) administration, Disintegration of stones by shock waves, contact dissolution with methyl-tert-butyl-ether
87
Acid Reflux
- Due to insuffiencient/defective LES
- Saliva neutralizes acid in Esophagus & induces 2ndary peristalsis for return to stomach
- May lead to Gastro-Esophageal Reflux Disease (GERD) - Chronic reflux, diminished LES, Pyrosis/heartburn, mucosal damage
88
Achalasia
- Loss of peristalsis & failure of LES to relax properly
- Cause: Autoimmune or infectional Ganglionic Cell destruction in Myenteric/Auerbach’s Plexus (Chagas Disease)
- Clinical features: Difficulty swallowing/Dysphagia, Aspirate food, Malnutrition, Halitosis/bad breath, Nocturnal food regurgitation
- Diagnosis: Manometry
- Treatment: Nifedipine, Nitrates, Botox (reduce LES tone), Myotomy (surgery), endoscopic LES ballon dilation (surgery)
89
Cystinuria
- Cysteine reabsorption decreased, Cysteine excreted in urine & recipitates in renal tubules in tract - Renal Stones
- Due to inherited transporter deficiency
- Asymptomatic until breaking point
90
Hartnup Disease
- Decreased Tryptophan dietary absorption & increased excretion
- Due to inherited defect in Tryptophan transport
- Manifestations: NAD+ deficiency (Pellagra)
- At risk: Low protein diet & lacking Niacin supplement
- Clinical features: Diarrhea, Dermatitis, Dementia, Death
91
Inherited Urea Cycle Disorders (UCDs)
- Deficiency of enzyme resulting in enzyme substrate accumulation
- Labs: Hyperammonemia (high blood Ammonia leveles), elevated Glutamine levels, decreased Urea formation
- Clinical features: Lethargy, Irritability, Feeding difficulties, Respiratory Alkalosis/Hyperventiation, Neurological manifestations - Seizures, Intellectual Disability, Developmental Delay
- Includes: Hyperammonemia Types I & II, Cirullinemia, Argininosuccinic Aciduria, Argininemia
- Treatment: Dialysis, Benzoic Acid or Phenylbutyrate/Phenylacetate Administration, Low protein high carb diet, Liver transplant, Present stresses that induce catabolic state, Arginine administration (except Argininemia)
92
Hyperammonemia Type I
- Inherited Urea Cycle Disorder (UCD)
- Deficiency: CPS I
- Labs: Hyperammonemia (most severes), low intermediates
- Clinical features: Lethargy, Irritability, Feeding difficulties, Respiratory Alkalosis/Hyperventilation, Seizures, Intellectual Disability, Developmental Delay
- Treatment: Arg. Supplementation, Dialysis, Benzoic Acid or Phenylbutyrate/Phenylacetate Administration, Low protein high carb diet, Liver transplant, Present stresses that induce catabolic state,
93
Hyperammonemia Type II
- Inherited Urea Cycle Disorder (UCD)
- Deficiency: OTC (Ornithine Transcarbamoylase)
- Most common, usually seen in males, X-linked
- Labs: Hyperammonemia, increased Orotic Acid urine excretion, Elevated Carbamoyl P, Increased Pyrimidine synthesis
- Clinical features: Lethargy, Irritability, Feeding difficulties, Respiratory Alkalosis/Hyperventilation, Seizures, Intellectual Disability, Developmental Delay
- Treatment: Dialysis, Benzoic Acid or Phenylbutyrate/Phenylacetate Administration, Low protein high carb diet, Liver transplant, Present stresses that induce catabolic state, Arginine administration (except Argininemia)
94
Citrullinemia
- Inherited Urea Cycle Disorder (UCD)
- Deficiency: Argininosuccinate Synthetase
- Labs: Hyperammonemia, increased Citrulline levels in blood & urine
- Clinical features: Lethargy, Irritability, Feeding difficulties, Respiratory Alkalosis/Hyperventilation, Seizures, Intellectual Disability, Developmental Delay
- Treatment: Dialysis, Benzoic Acid or Phenylbutyrate/Phenylacetate Administration, Low protein high carb diet, Liver transplant, Present stresses that induce catabolic state, Arginine administration (except Argininemia)
95
Argininosuccinic Aciduria
- Inherited Urea Cycle Disorder (UCD)
- Deficiency: Argininosuccinate Lyase (ASL)
- Labs: Hyperammonemia, increased Argininosuccinate in plasma & urine, elevated Citrulline
- Clinical features: Lethargy, Irritability, Feeding difficulties, Respiratory Alkalosis/Hyperventilation, Seizures, Intellectual Disability, Developmental Delay
- Treatment: Dialysis, Benzoic Acid or Phenylbutyrate/Phenylacetate Administration, Low protein high carb diet, Liver transplant, Present stresses that induce catabolic state, Arginine administration (except Argininemia)
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Argininemia
- Inherited Urea Cycle Disorder (UCD)
- Deficiency: Arginase
- Labs: Mild Hyperammonemia, Hyperargininemia/increased Arginine
- Onset: Late/adult - Clinical features: Lethargy, Irritability, Feeding difficulties, Respiratory Alkalosis/Hyperventilation, Seizures, Intellectual Disability, Developmental Delay
- Treatment: Dialysis, Benzoic Acid or Phenylbutyrate/Phenylacetate Administration, Low protein high carb diet, Liver transplant, Present stresses that induce catabolic state
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Phenylketonuria (PKU)
- AR
- Diagnosis: Guthrie test or Mass Spec
- Clinical features: Milestone delay, Low IQ, Seizures, Spacticity, Autistic behaviors, mousey odor urine, decreased skin & hair pigmentation
- Labs: Phenylpuruvate/Phenylacetate/Phenyllactate in urine
- Treatment: Low Phenylalanine diet (modified medical food, low protein), avoid Aspartame (artificial sweetener), Sapropterin (synthetic BH4)
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Maternal PKU
- Fetal defects: Microcephaly, neurological problems, congenital heart defects, facial dysmorphology (similar to fetal alcohol syndrome - long philtrum, epicantal folds, micrognathia, short nose, microopthalmia, flat midface)
- Biochemical defect: Hydrobipterin synthesis/Dihydrobiopterin reductase deficiency (BH4) - needed for ring hydroxylation reactions
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Alkaptonuria
- Inborn error of Phe-Tyr Catabolism
- Deficiency: Homogentisic Acid Oxidase (Homogentisic acid —> Maleylacetoacetate)
- Accumulation: Homogentisic Acid
- Clinical features: Arthritis, darkening of urine on standing, blue discoloration of cartilage & CT (Sclera), Ochronotic pigments (HA deposits in cartilage & CT)
- Treatment: Dietary restriction of Phe & Tyr
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Tyrosinosis
- Tyrosinemia Type I
- Inborn error of Phe-Tyr Catabolism
- Deficiency: Fumarylacetoacetate Hydrolase
- Accumulation: Fumarylacetoacetate
- Clinical features: Kidney & Liver damage, caggage-like urine smell
- Treatment: Dietary restriction of Phe & Tyr, Nitisinone (NTBC; inhibits PDO) therapy, Liver transplant
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Maple Syrup Urine Disease (MSUD)
- Inborn error of metabolism - branched chain AA
- Cause: BCK (Branched Chain Ketoacid) Dehydrogenase defect
- Ketoacid increase are neurotoxic
- Cofactor: TPP
- Diagnosis: Neonatal/newborn screening
- Mild & Secere forms
- Clinical features: Hypotonia & Hypertonia (alternating), Seizures, Encephalopathy, Ketosis, Urine odor, Psychomotor developmental delay, progressive neurological disease, recurrent Ketoacidotic episodes
- Treatment: 20% Glucose with Insulin IV (Acute), Dietary restriction of BCAAs (Long term), Thiamine supplementation, avoid catabolic states
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Methylmalonyl CoA Mutase Deficiency
- Elevated Methylmalonic Acid levels in circulation
- Labs: GC/MS urinary analysis
- Clinical features: Metabolic Acidosis (Ketosis & Ketoacidosis), Seizures, Encephalopathy
- Treatment: VitB12/Cobalamin supplementation, dietary BCAAs restriction/reduction
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Homocystinuria
- Homocystein metabolism defect
- AR
- Deficiency: Cystathionine B-Synthase (Transulfuration Pathway)
- Clinical features: Ectopia Lentis (Lens discoloration - down & in), Marfanoid Habitus (skeletal abnormalities), mental retardation, premature Arterial Disease, Osteoporosis, Atheromas (lipid deposits), Fibrosis & Plaque Calcification (lipid oxidation & platelet aggregation), limited joint mobility
- Labs: High plasma & urinary Homocystine
- Treatment: Oral VitB6/Pyridoxine, Dietary protein restriction, Met-free food, Met supplementaion, Oral Betaine-HCl
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Folate Deficiency
- Reduction in 1-C donors —> reduced synthesis of Purine & Pyrimidine nucleotides
- DNA synthesis delay —> reduced rates of cells division
- Blood smear: Polysegmented neutrophils, Macrocytes, Megaloblasts
- High risk groups: Pregnancy (neural tube defects), Chronic alcoholics, Veggie avoidance persons
- Clinical features: Macrocytic & Megaloblastic Anemia
- Diagnosis: Histidine load test - FIGLU in urine
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Vitamin B12 Deficiency
- Labs: Increased Methylmalonate in circulation & urine, elevated Homocysteine, Folate Trap - Methyl THF
- Clinical features: Macrocytic & Megaloblastic Anemia (Folate trap), Neuro. Damage (myelin), CV disease/hyperhomocysteinemia, tingling hand/feet, inability to walk, psychiatric disturbances, urinary incontinence
- Risk factors: Strict Vegans, Atrophic Gastritis, Pernicious Anemia (parietal cell autoimmune destruction), Ileum Disease (TB, Chron’s)
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Acute Intermittent Porphyria / AIP
- Deficiency: PBG Deaminase / HMG Synthase / Uroporphyrinogen I Synthase
- Accumulate: ALA / Delta-Aminolevulinic Acid & Porphobilinogen / BPG
- Clinical features: Severe abdominal pain, colic, constipation, lower extremity weakness, systemic arterial hypertension, agitated state, mental disturbance, tachycardia, respiratory problems, (not photosensitive)
- Urinalysis: Increased ALA & Porphobilinogen levels - urine turns dark red/purple/black upon standing with contact with air or light
- Risk factors: Heme synthesis drugs, infections, ethanol abuse, estrogen hormone therapy, caucasians, women 20-40
- Treatment: Saline & IV Glucose / Hemin (reduce ALA-S1 expression), No Barbituates (stimualte CP450 leading to toxic ALA levels)
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Congenital Erthropoietic Porphyria / CEP
- Deficiency: Erythroid Isozyme of Uroporphyrinogen III Synthase —> No HMG ring closure
- Accumulation: Uroporphyrin I & Coproporphyrin I
- Affecting organ: Bone Marrow
- Clinical features: Skin Photosensitivity, poor wound healing, blisters, ulcers, reddish/brown teeth, Hypertrichosis (werewolf features - hairy arms & legs)
- Urinalysis: Red colored urine
- Onset: Childhood (AR)
- Treatment: Bone marrow transplant, (Hemin IV not effective - ALA-S2 not inhibited)
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Porphyria Cutanea Tarda / PCT
- Deficiency: Uroporphyrinogen III Decarboxylase
- Accumulation: Uroporphyrin III accumulation
- Affecting Organs: Liver, Blood, Skin
- Clinical features: Photosensitivity, cutaneous lesions
- Urinalysis: Urine is red upon release, light pink in fluorescent light
- Onset: 40-50
- Types: 1 - aquired due to chronic liver dx (hepatitis, ethanol abuse), 2 - familial
- Treatment: Avoid sunlight & alcohol, reduce dietary Iron uptake
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Prehepatic/Hemolytic Jaundice
- Increased RBC breakdown/decreased lifespan
| - Labs: Increased total Bilirubin, Increased unconjugated Bilirubin, Increased Urobilinogen
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Hepatocellular Jaundice
- Labs: Increased total serum Bilirubin, Increased serum conjugated Bilirubin, Increased serum unconjugated Bilirubin, Elevated AST & ALT, Bilirubin & Urobilinogen present in urine
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Posthepatic/Obstructive/Cholestatic Jaundice
- Labs: Increased total serum Bilirubin, increased conjugated Bilirubin, absent/low Urobilinogen, urine Bilirubin present, decreased Sterocolbilin excretion in feces (clay colored), elevated APL & GGT
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Kernicterus
- Jaundice in newborns
- Serum Bilirubin >25 mg/dL
- Unconjugated Bilirubin crosses underdeveloped blood-brain barrier & forms deposits in Basal Ganglia
- Clinical features: Lethargy, altered muscle tone, high-pitched cry, neurologic symptoms - choreoathetosis, spasticity, muscular rigidity, ataxia, intellecual impairment
- At risk: Hypoalbuminemia, low pH, drugs - Salicylates, Sulfonamides
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Cringler-Najjar Syndrome Type I
- Inherited Unconjugated Hyperbilirubinemia
- Low UDP Glucouronyl Transferase enzymatic activity: <5% (Most severe form)
- Serum Unconjugated Bilirubin levels: 50 mg/dL
- Clinical features: Jaundice in neonate/infant, Kernicterus & Developmental delay, fatal if untreated
- Treatment: Phototherapy, exchange transfusion (to prevent Kernicterus) (Unresponsive to Phenobarbital)
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Crigler-Najjar Syndrome Type II / Arias Syndrome
- Inherited Unconjugated Hyperbilirubinemia
- Low UDP Glucouronyl Transferase enzymatic activity: 10%-20%
- Serum Unconjugated Bilirubin levels: 6-22 mg/Dl
- Clinical features: Jaundice
- Treatment: Phenobarbital, regular phototherapy
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Gilbert Syndrome
- Inherited Unconjugated Hyperbilirubinemia
- UDP Glucouronyl Transferase enzymatic activity: 50%
- Serum Unconjugated Bilirubin levels: 2-5 mg/dL
- Clinical features: Mild Jaundice (following illness, stress, starvation)
- Presentation: 3%-7% of population, mainly in adolescents & young adults
- Labs: Normal AST, ALT, ALP
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Dubin Johnson Syndrome
- Inherited Unconjugated Hyperbilirubinemia - inherited ABC Transporter deficiency
- Presentation: Adolescents & young adults
- Labs: Elevated conjugated Bilirubin, Normal AST, ALT, ALP
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Methanol Toxicity
- Methanol (byproduct of excessive alcohol consumption) oxidixed via Alcohol Dehydrogenase to Formaldehyde (toxic) inside Liver, Neurons, & Retinal cells
- Clinical features: Mental & visual disturbances (snowstorm effect), Metabolic Acidosis, Blindness, Death
- Treatment: Ethanol (higher affinity), Fomepizole (ADH competitive inhibitor), Bicarbonate (Metabolic Acidosis Tx), Hemodialysis (Metabolic Acidosis Tx)
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Ethylene Glycol Toxicity
- Ethylene Glycol (found in Antifreeze) oxidized to Glycoaldehyde (toxic) via Alcohol Dehydrogenase, which leads to Glycolic Acid which is changed to Oxalic Acid
- Clinical features: Metabolic Acidosis, cerebral & renal damage, hypocalcemia, death
- Treatment: Fomepizole or Ethanol (ADH inhibition), Calcium Carbonate (Metabolic Acidosis Tx), Hemodialysis & Respirator
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Stigmata of Chronic Cirrhosis
- Spider Angioma
- Ascites - due to decreased Albumin & portal Hypertension
- Gynecomasatia - due to inactivated Testosterone & aromatase conversion to Estrogen
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Vitamin A Deficiency
- Risk factors: Dietary deficiency (fat free diet, lack of sources), Fad diets, Fat Malabsotpion (CF, Obstructive Jaundice)
- Clinical features: Night blindness (delayed Rhodopsin regeneration), Xeropthalmia (conjunctive & cornea dryness), Blind spots, Keratomalacia (corneal erosion & ulceration), Increasaed pulmonary infection risk, Immune deficiency (weak innate immunity)
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Vitamin A Clinical Uses
- Retinol or B-Carotene: Detary defiency treatment
- Retinoid Acid: Acne treatment
- Trans Retinoic Acid: Acute Promyelocytic Leukemia treatment
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Hypervitaminosis A
- Clinical features: Dry/pruritic/itchy/peeling skin, benign intracranial hypertension, headache
- Labs: Hepatomegaly & altered LFTs
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Vitamin D Deficiency
- Labs: Low serum Ca & P, decreased bone mineralization
- Risk factors: Inadequate sunlight exposure, nutritional deficiency (decreased intake, fat malabsorption, exclusively breastfed babies), chronic renal failure, chronicl liver disease
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Rickets
- Vit D deficiency in children
- Clinical features: Bow-leg deformity, enlarged epiphysis at wrist & ankles, rachitic rosary (costochondroal junction overgrowth), pigeon chest deformity, frontal bossing (delayed fontanelle closing), delayed teethin in infants, kyphosis, curved femur & humerus, soft/pliable bones
- Labs: Elevated serum ALP, low serum Ca & P, increased Parathyroid hormone release, increased demineralization of bone
- Treatment: Vit D & Ca supplementation
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Osteomalacia
- Vit D Deficiency in adults
- Risk factors: Reduced sunlight exposure, dietary deficiency, renal or liver disease
- Clinical features: Demineralized bones & susceptible to fracture, non-specific bone pain
- Labs: Elevated serum ALP, low Ca & P
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Hypervitaminosis D
- Increased tendency for ectopic/soft tissue mineralization, Hypercalcemia
- Prolonged prescription medications lead to calcification in soft tissues
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Vitamin K Deficiency
- Risk factors: Fat malabsorption (CF), prolonged used of broad-spectrum antibiotics
- Clinical features: Hematuria, Melena (black tarry stools), Ecchymoses (brusing), Bleeding gums
- Labs: Increased INR (Prothrombin time)
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Scurvy
- Vit C Deficiency
- Due to decreased hydroxyl groups/fewer Hydrogen bonds in Collagen
- Clinical features: CT defects, Perifollicular hemorrhage (fragile BVs), sore bleeding gums, loose teeth, frequent bruising, impaired/delayed wound healing
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Beriberi
- Thiamine (Vit B1) Deficiency
- Affects Brain & Cardiac Muscle (aerobic tissues)
- Clinical features: Polyneuropathy (Dry), Cardiovascular (Wet)
- Labs: Low erythrocytes transketolase activity, serum Thiamine
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Wernicke-Korsakoff Syndrome
- Vit B1/Thiamine deficiency
- Cause: Chronic alcoholism
- Clinical features: Neurologic manifestations, Ophthalmoglegia, Nystagmus, Ataxia, Confusion, Disorientation, Memory Loss, Confabulation
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Riboflavin (Vit B2) Deficiency
- Cause: Nutritional
- Clinical features: Cheiolosis (pallor, cracks, fissures at mouth angles), Glossitis (tongue inflammation & atrophy), Facial Dermatitis
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Niacin (Vit B3) Deficiency
- Clinical features: Pellagra - Dermatitis (skin), Diarrhea (GIT), Dementia (CNS), Death
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Pyridoxine (Vit B6) Deficiency
- Risk factors: Isoniazid therapy (Anti-TB drug) - inactivates Pyridoxine
- Treatment: Pyridoxine supplements & INH
- Clinical features: Microcytic anemia (reduced heme synthesis - low ALAS), Peripheral Neuropathy (reduced neurotransmitter synthesis), Increased CVD risk (high homocysteine), Seizures (reduced neurotransmitter synthesis)
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Cobalamin/Vit B12 Deficiency
- Clinical features: Anemia, Neurological features - extremity tingling & numbness (due to Methylmalonate accumulation - myelination)
- Anemia: Macrocytic (increased MCV) & Megaloblastic (bone marrow); due to Folate Trap
- Labs: Increased MCV, Elevated serum Homocysteine, Elevated Methylmalonate, Reduced serum Vit B12
- Risk factors: Lack of IF, Parietal cell destruction (Pernicious Anemia), Ileal mucosal disease/resection, Vegan diet
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Folate Deficiency
- Clinical features: Macrocytic Anemia, No neuro features
- Anemia: Macrocytic (increased MCV) & Megaloblastic (Bone marrow); due to Folate deficiency
- Labs: Increased MCV, Elevated Homocystine, Normal serum Methylmalonate, Reduced serum Folate, Normal Vit B12
- Risk factors: Malabsorption Syndrome/Intestinal Mucosal Disease, Pregnancy, Dietary lack of green leafy veggies, Folate antagonist treatment (Methotrexate - Dihydrofolate Reductase Inhibitor)
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Lysosomal Storage Disorders (LSD) Common Features
- Mostly AR (exception of X-linked)
- Commonly affects infants & young children
- Clinical features: Hepatosplenomegaly (insoluble intermediates stored), Neuronal damage, Cell dysfunction (undigested material stored, macrophages activated, cytokines release)
- Diagnosis: Enzyme assay in Leukocytes or Fibroblasts
- Includes (Classification): Huler Syn. (Mucopolysaccharidose), Hunter Syn. (Mucopolysaccharidose), Tach-Sachs (Sphingolipidose), Gauchers Dx (Sphingolipidose), Fabry Dx (Sphingolipidose), Neimann-Pick Dx (Sphingolipidose), Metachromatic Leukodystrophy (Sphingolipidose), Pompe’s Dx (Glycogen Storage Dx), GSD II (Glycogen Storage Dx), I-Cell Dx
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Mucopolysaccharidoses
- Type of LSD
- Deficiency: Enzyme required for GAG degradation
- Accumulating sustrate: Dermatan Sulfate & Heparan Sulfate (GAGs)
- Degradation: By Lysosomes by removing 1 sugar at a time
- Treatment: Enzyme Replacement Therapy
- Includes: Hunter Syndrome & Hurler Syndrome
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Hurler Syndrome
- LSD - Mucopolysaccharidose (MPS I H)
- Deficiency: Alpha-L-Iduronidase
- Accumulating Substrates: Dermatan Sulfate & Heparan Sulfate (GAGs)
- Severity: Most
- Clinical features: Corneal clouding, Mental retardation, Dwarfism, Coarse dysmorphic facial features, Upper airway obstruction, Hearing loss, Short stature, Hepatosplenomegaly, Restricted joint mobility, Ischemia, Early death
- Diagnosis: Fibroblast assay
- Urinalysis: Positive for GAGs
- Treatment: Bone marrow or cord blood transfusion, Iduronidase enzyme replacement therapy
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Hunter Syndrome
- LSD - Mucopolysaccharidose (MPS)
- Deficiency: Iduronate Sulfatase
- Accumulating substrates: Dermatan Sulfate & Heparan Sulfate (GAGs)
- Severity: Milder MPS
- Inheritance: X-Linked
- Clinical features: No corneal clouding, Physical deformity, Coarse facial features, Mental Retardation (mild to moderate), Hepatosplenomegaly
- Treatment: Hepatopoietic stem cell therapy, Enzyme replacement therapy
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Sphingolipidoses
- Type of LSD
- Characterization: Group of complex lipids containing alcohol Sphingosine instead of Glycerol
- Sphingosine + FA = Ceramide
- Classification: Glycosphingolipid/Glycolipid (contain Carb moiety linked to Ceramide) & Sphingophospholipid (contain Phosphoryl Choline moiety linked to Ceramide - Sphingomyelin)
- Includes: Tay-Sachs Disease, Gauchers Disease, Fabry Disease, Diemann-Pick Disease, Metachromatic Leukodystrophy
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Tay-Sachs Disease
- LSD - Spingolipidose
- Deficiency: Beta-Hexosaminidase A
- Accumulating substrates: Ganglioside GM2
- Clinical features: Progressive neurodegeneration (3-6 months), Blindness, Developmental milestone regression, Fatal by 2-6
- Labs/Microscopy: Lysosomal onion-shell inclusions, Cherry-red spot on Macula (neuron destruction)
- Carrier Detection (heterozygous): Enzyme assays
142
Gaucher Disease
- LSD - Spingolipidose
- Deficiency: Beta Glucosidase
- Accumulating substrate: Glucosyl Cermaide (Glucocerebroside)
- Most common LSD, commonly seen in Adults
- Clinical features: Hepatosplenomegaly, Osteoporosis, No neurological damage
- Histologic features: Cytoplasm enlarged, elongated, filled with Glucocerebroside - like “crumpled tissue paper”
- Imaging: Distal Femur shaped like Erlenmeyer flask
- Treatment: Enzyme replacement therapy
143
Fabry Disease
- LSD - Spingolipidose
- Deficiency: Alpha Galctosidase
- Accumulating substrate: Globoside/Ceramide Trihexose (in skin, kidneys, nerves, heart)
- Inheritance: X-linked recessive
- Clinical features: Peripheral neuropathy (tingling, buring extremities, acroparesthesia), Kidney damage, Heart attack, Stroke
144
Neimann Pick Disease
- LSD - Spingolipidose
- Deficiency: Sphingomyelinase
- Accumulating substrate: Sphinomyelin/Sphingophospholipid (in neuronal tissue)
- Types/Clinical features: A - severe, infantile presentation, fatal by 2-3, red spot on macula/blindness; B - childhood presentation, hepatosplenomegaly
- Histological features: Foamy cell appearance/Lipid droplet accumulation
145
Metachromatic Leukodystrophy
- LSD - Spingolipidose
- Deficiency: Aryl Sulfatase A
- Accumulating substrate: Sulfatide (neuron rich)
- Clinical features: Progressive paralysis, Demyelination
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Pompe’s Disease
- LSD - GSD
- Cellular Glycogen degraded by Lysosomal Acid Maltase (1 Glucosidase —> 4 Glucosidase)
- Accumulating substrate: Glycogen as vacuoles in lysosomes (in heart: cardiac failure, in muscle: myopathy, in kidney, in liver: hepatocellular damage)
- Clinical features: Frog-like posture
-
147
I-Cell Disease
- LSD
- Deficiency: Mannose 6-P - Ability to phosphorylate Mannose —> Defective Lysosome enzyme trafficking
- Accumulating substrate: GAGs & Sphingolipids in Lysosomes
- Clinical features: Skeletal abnormalities, Restricted joint movement, Coarse facial features, Psycomotor impairment, Death ~8 years old, Small orbits, Proptic eyes, Full/prominent mouth (Gingival Hypertrophy), short branched hands, Hepatosplenomegaly, Umbilical hernia, Limited hip & knee extension (similar to Hurlers except more severe & earlier age of onset)
- Histological features: Fibroblast intracytoplasmic inclusions
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Copper Deficiency
- Clinical featuers: Microcytic Anemia (Ceruloplasmin/Ferroxidase affects Iron mobilization), Increased bleeding/Hemorrhage (decreased Lysyl Oxidase, degraded vascular tissue), Hypopigmented hair
- Labs: Low serum Copper, Low MCV
149
Menkes Syndrome
- Deficiency: Dietary Copper absorption
- Inheritance: X-linked
- Clinical features: Kinky gray hair (Tyrosinase), Aneurysms, Neurological dysfunction (low Lysyl Oxidase), Early age of presentation (1-2 years)
150
Wilson Disease
- Mutation: ATP7B (Copper Transporting ATPase gene) - Cupper attaches to Ceruloplasmin & excreted in Bile
- Accumulation: Copper in liver, brain, eye
- Inheritance: AR, allelic heterogeneity
- Clinical features: Hepatitis & Cirrhosis, Kayser Fleischer corneal rings, Neuropsychiatric symptoms
- Labs: Decreased serum Ceruloplasmin, increased Copper excretion in urinalysis, increased hepatic Copper
151
Hemochromatosis Labs Values
High serum Ferritin, High serum Iron, Low TIBC (Total Iron Binding Capacity), High Transferrin Saturation
152
Anemia Lab Values
Low serum Ferritin, Low serum Iron, High TIBC, Low Transferrin Saturation
153
Iron Deficiency Anemia
- Cause: Nutritional deficiency (vegans, low dietary vitamin C, Achlorhydria (low stomach pH), high dietary fiber)
- At risk: Pregnancy, infants, blood donors
- Clinical feature: Chronic bleeding, Hypochromic microcytic anemia, fatigue, pallor, weakness, dizziness, brittle nails, pica
- Labs: Low serum Ferritin, low serum Iron, low Transferrin saturation %, increased TIBC, low Hemoglobin/Hematocrit, low MCV, low MCHC, low bone marrow iron stores
- Dietary management: Iron rich foods, increase Vit C (heme iron - animal sources), reduce fiber
154
Dietary Hemochromatosis
- Excessive Iron absorption in skin, liver, pancreas
- Cause: C282Y gene HFE mutation (allelic heterogeneity, compound heterozygote)
- Inheritance: AR
- Clinical features: Variable expressivity (males > females), delayed age of onset
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Hereditary Hemochromatosis
- Excess Iron causing free radical formation & DNA damage
- Clinical features: Acute synovitis/Chronic joint pain (knuckles), Chronic fatigue, Hepatomegaly, Cirrhosis, Hepatocellular carcinoma, Diabetes, Cardiac dysfunction, Bronze Diabetes
- Labs: High serum Ferritin, high serum Iron, high Transferrin % Saturation, low TIBC
- Management: Phelobotomy, Dietary modification - reduce red meat & increase fiber
