Genetic diseases Flashcards
1
Q
Achondroplasia
Mode of inheritance, Cause(s), Presentation
A
- Autosomal dominant; full penetrance; most common cause of dwarfism
- Mutation of fibroblast growth factor receptor 3 (FGFR3) inhibits chondrocyte proliferation
- Dwarfism (short limbs, larger head, trunk size is normal)
2
Q
Adult polycystic kidney disease (APKD)
Mode of inheritance, Cause(s), Presentation, Association(s)
A
- Autosomal dominant
- Chrom. 16 mutation of PKD1 gene (85%), Chrom. 4 mutation of PKD2 gene (15%)
- Bilateral flank pain, hematuria, hypertension, progressive renal failure
- Associated with polycystic liver disease, berry aneurysms, MVP.
3
Q
Familial adenomatous polyposis
Mode of inheritance, Cause(s), Presentation
A
- Autosomal dominant
- Chrom. 5 mutation of APC gene
- Starts after puberty when the colon becomes covered with adenomatous polyps and progress to colon cancer unless colon is resected
4
Q
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
(Mode of inheritance, Cause(s), Presentation, Association(s))
A
- Autosomal dominant
- Mutations involving receptors of transforming growth factor beta-1 (TGF-beta-1) (usually frameshift mutations); a variant was found that also is linked with juvenile polyposis (mutation in an intracellular signaling protein of TGF superfamily receptors)
- Telangiectasia, recurrent epistaxis, skin discoloration, AV malformations (lungs [50%], liver [30-70%], and brain [10%])
- Portal hypertension, hepatic encephalopathy, and intracranial hemorrhage
5
Q
Hereditary spherocytosis
Mode of inheritance, Cause(s), Presentation, Diagnosis, Treatment
A
- Autosomal dominant
- Spectrin, ankyrin, or band 3 protein (red blood cell surface proteins) defect
- Hemolytic anemia, with jaundice and splenomegaly
- Dx: Increased MCHC and RDW
- Rx: Splenectomy is curative
6
Q
Huntington’s disease
Mode of inheritance, Cause(s), Presentation
A
- Autosomal dominant
- Chrom. 4 mutation in Huntigtin (HTT) gene, (CAG) trinucleotide repeat, with degeneration of spiny neurons in Caudate nucleus with decrease levels of GABA and Ach, and increased dopamine
- Chorea, depression, progressive dementia, and psychosis
7
Q
Marfan syndrome
Mode of inheritance, Cause(s), Presentation, Association(s)
A
- Autosomal dominant
- Chr. 15 mutation in FBN1 gene encodes for fibrillin 1 (a glycoprotein that acts as a scaffold for alignment of elastic fibers & down regulator of transforming growth factor beta [TGF-beta])
- Tall with long extremities, pectus excavatum, pectus carinatum (pigeon chest), hypermobile joints, long fingers (arachnodactyly)
- Associated with cystic medial necrosis of aorta (ascending aortic dissection [most common cause of death]), mitral valve prolapse (most common complication), dilatation of aortic ring (potentially lead to aortic valve insufficiency) and subluxation of lenses (upward and outward)
8
Q
Multiple endocrine neoplasias (MEN)
Mode of inheritance, Cause(s), Presentation
A
- Autosomal dominant
- MEN1 gene mutation for MEN 1, RET gene mutation for MEN 2a and 2b, RET and NTRK1 genes muations for familial medullary thyroid carcinoma ([FMTC] a form of MEN 2)
- Presentation:
- MEN 1 (3 Ps): Tumors of pancreas, parathyroid, and pituitary
- MEN 2a (2 Ps and 1 M): pheochromocytoma, parathyroid and medullary thyroid carcinoma
- MEN 2b (1 P and 2 Ms): pheochromocytoma, medullary thyroid carcinoma and marfanoid habitus/mucosal neuroma
9
Q
Neurofibromatosis type 1 (von Recklinghausen’s disease)
Mode of inheritance, Cause(s), Presentation, Association(s), Diagnosis, Treatment
A
- Autosomal dominant; 90% of all NF (1:3000)
- Chrom. 17 mutation of NF1 gene (tumor suppressor gene) that is normally produce a protein called neurofibromin that inhibits p21 ras oncoprotein
- Cafe au lait spots (6 or more), multiple neurofibromas which are benign but cab be disfiguring, Lisch nodules (pigmented iris hamartomas), the plexiform variant is diagnostic
- There is risk of 3% malignant transformation of neurofibromas, increased risk of meningiomas and pheochromocytoma, and association with scoliosis and optic pathway gliomas
- Dx: x-ray, CT scan and MRI, genetic testing and EEG
- Rx: surgical removal, and chemotherapy for optic pathway gliomas
10
Q
Neurofibromatosis type 2 (Bilateral acoustic)
Mode of inheritance, Cause(s), Presentation, Association(s), Diagnosis
A
- Autosomal dominant; 10% (1:45,000)
- Chrom. 22 mutation of NF2 gene (tumor suppressor gene) that is normally produce a protein called merlin which is a critical regulator of contact-dependent inhibition of proliferation
- Cafe au lait spots and neurofibromas (smaller and fewer than type 1), with bilateral acoustic tumor (schwannomas of CN VIII) that may lead to hearing loss and balance problems
- Associated juvenile cataracts, and increased risk of meningiomas and ependymomas
- Dx: x-ray, CT scan and MRI, genetic testing and EEG
11
Q
Tuberous sclerosis
Mode of inheritance, Cause(s), Presentation, Association(s)
A
- Autosomal dominant; Incomplete penetrance, variable presentation
- Mutation of either TSC1 which encodes for hamartin or TSC2 which encodes for tuberin (both are tumor growth suppressor genes)
- Hamartomas, Adenoma sebaceum, hypopigmented “ash leaf spots” on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts and renal angiomyolipomas, cardiac rhabdomyomas
- Increased incidence of astrocytomas (from subependymal nodules) and epilepsy
12
Q
von Hippel-Lindau disease
Mode of inheritance, Cause(s), Presentation, Association(s), Diagnosis
A
- Autosomal dominant
- Chrom. 3 mutation of VHL gene (tumor suppressor) that is normally produce proteins that tag proteins like hypoxia inducible factor ([HIF] a transcription factor that induces the expression of angiogenesis factors) with ubiquitin for degradation
- Hemangioblastomas of retina (von Hippel tumor), cerebellum, brain stem, and spinal cord (Lindau tumor), also cysts of liver, pancreas, and kidneys
- Associated with bilateral renal cell carcinoma, pheochromocytoma, and polycythemia (due to erythropoietin secreting hemangioblastomas [especially of cerebellum])
- Dx: at least two tumors in persons without family history, southern blot and gene sequencing
13
Q
Cystic fibrosis (Mucoviscidosis) (Mode of inheritance, Cause(s), Presentation, Association(s), Diagnosis, Treatment)
A
- Autosomal recessive
- Chr. 7 mutation of CFTR gene, deletion of Phe 508 (delta F508) which interferes with proper protein folding and post-translational processing of oligosaccharide chain. the abnormal chloride channel protein is degraded by cytosolic proteasome complex rather than translocated to cell membrane
- Recurrent pulmonary infection (Pseudomonas [adolescence] and S. aureus [early infancy]), chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steatorrhea), nail clubbing and nasal polyps
- Associated with male infertility due to bilateral absence of vas deferens and epididymis, subfertility in women (amenorrhea, abnormally thick cervical mucus), fat soluble vitamin deficiencies, vitamin B12 deficiency, biliary cirrhosis and meconium ileus in newborns
- Diagnosis is by sweat test (elevated NaCl [Cl > 60 mEq/L]) or DNA probes. Contraction alkalosis and hypokalemia. Increase immunoreactive trypsinogen (newborn screening)
- Rx: Chest physiotherapy, albuterol, aerosolized dornase alpha (DNAse) and hypertonic saline to facilitate mucus clearance. Azithromycin used as anit-inflammatory agent. Pancreatic enzymes for insufficiency
14
Q
Duchenne muscular dystrophy
Mode of inheritance, Cause(s), Presentation, Association(s), Diagnosis
A
- X-linked recessive
- Usually due to Frameshift or nonsense mutations leading to deletion of Dystrophin gene (DMD) [the longest known human gene] —> truncated dystrophin (which helps anchor muscle fibers by connecting intracellular cytoskeleton (actin) to transmembrane proteins alpha- and beta-dystroglycan, which are connected to extracellular matrix) —> inhibited muscle regeneration and myonecrosis
- Starts before age of 5 as weakness of pelvic girdle and progress superiorly, pseudohypertrophy of calf muscles (due to fibrofatty replacement), Gower maneuver: patients use upper extremities to help them stand up, waddling gait
- Dilated cardiomyopathy which is a common cause of death
- Dx: Increased CK and aldolase, Western blot and muscle biopsy confirm diagnosis
15
Q
Becker’s muscular dystrophy
Mode of inheritance, Cause(s), Presentation, Association(s), Diagnosis
A
- X-linked recessive
- Typically non-frameshift insertions in DMD gene (which lead to partially functional dystrophin)
- Less severe than Duchenne and starts in adolescence or early adulthood
- Dilated cardiomyopathy which is a common cause of death
- Dx: Increased CK and aldolase, Western blot and muscle biopsy confirm diagnosis
16
Q
Fragile X syndrome
Mode of inheritance, Cause(s), Presentation, Association(s), Diagnosis
A
- X-linked dominant; Second most common cause of genetic mental retardation
- Defect in methylation and expression of the FMR1 gene with trinucleotide repeat (CGG)
- Macro-orchidism, long face with a large jaw, large everted ears
- Autism and MVP
- Dx: DNA probes
17
Q
Down syndrome (trisomy 21) 1:700 (Cause(s), Distinguishing Features, Associations, Diagnosis)
A
- 47 XX or XY +21; 95% meiotic nondisjunction of homologous chromosomes during meiosis I (advanced maternal age; 1:25 if > 45), 4% Robertsonian transloction and 1% Down mosaicism due mitotic nondisjunction
- Mongoloid facies( low-bridge nose [flat], prominent epicanthal folds), simian crease, Brushfield spots (speckled appearance of iris), gap between 1st and 2 toes
- Associated with congenital heart anomalies (e.g., AV septal defect, ASD), duodenal atresia (projectile, bilious vomiting), Hirschsprung disease, increase risk of ALL (ages 3-7), AML-M7 (age < 3) & Alzheimer disease (>35)
- Diagnosis:
- After birth: karyotype using FISH
- First trimester U/S commonly shows increased nuchal translucency and hypoplastic nasal bone; decreased serum PAPP-A and increased free beta-hCG. Also Cell Free Fetal DNA (CFFD) by PCR to detect any trisomy and determine sex of baby
- Second trimester: quad screen (decreased alpha fetoprotein & unconjugated estriol with increase in beta- hCG and inhibin A)
18
Q
Edward’s syndrome (trisomy 18) 1:8000
Cause(s), Distinguishing Features, Associations, Diagnosis
A
- 47 XX or XY +18; meiotic nondisjunction of homologous chromosomes during meiosis I
- Rocker-bottom feet, overlapping flexed fingers, micrognathia (small jaw), low set ears, and congenital heart disease
- Horse-shoe kidney; death usually occurs within 1 year of birth
- Diagnosis:
- After birth: karyotype using FISH
- First trimester: decreased PAPP-A and free beta-hCG
- Second trimester: quad screen (decrease in alpha fetoprotein, beta hCG, estriol, and decreased or normal inhibin A)
19
Q
Patau’s syndrome (trisomy 13) 1:15000
Cause(s), Distinguishing Features, Associations, Diagnosis
A
- 47 XX or XY +13; meiotic nondisjunction of homologous chromosomes during meiosis I
- Cleft lip/palate, holoprosencephaly (single cerebral hemisphere), polydactyly, cyclopia, congenital heart disease
- None; death usually occurs within 2 weeks after birth
- Diagnosis:
- After birth: karyotype using FISH
- First trimester decrease free beta hCG and PAPP-A
20
Q
Cri-du-chat syndrome
Cause(s), Distinguishing Features, Associations, Diagnosis
A
- 46 XX or XY 5p-; due to congenital microdeletion of short arm of Chrom. 5
- Microcephaly, moderate to severe mental retardation, high pitched crying, epicanthal folds
- Cardiac abnormalities (VSD)
- Diagnosis: after birth with karyotype using FISH
21
Q
Williams syndrome
Cause(s), Distinguishing Features, Associations, Diagnosis
A
- 46 XX or XY 7q-; due to congenital microdeletion of long arm of Chrom. 7 (deleted region includes elastin gene)
- Distinctive “elfin” facies (puffy eyes, blue eyes with starry pattern, long philtrum, small and widely placed teeth), intellectual disability (mild to moderate), hypercalcemia (increased sensitivity to vitamin D), well developed verbal skills, extreme friendliness with strangers, hyperacusis (sensitive hearing)
- Cardiovascular problems (supravalvular aortic stenosis, supravalvular pulmonary stenosis), and ADHD
- After birth with karyotype using FISH
22
Q
22q11.1 deletion syndrome (previously known as Di George syndrome or Velocardiofacial syndrome)
(Cause(s), Distinguishing Features, Associations, Diagnosis)
A
- Microdeletion at Chrom. 22q11, inherited as AD with incomplete penetrance; abnormalities are due to aberrant development of 3rd and 4th branchial pouches
- CATCH-22: Cleft palate, Abnormal facies, Thymic aplasia (T-cell deficiency), Cardiac defects (interrupted aortic arch, truncus arteriosus and tetralogy of Fallot), Hypocalcemia and Hypoparathyroidism
- Hearing loss (both conductive and sensorineural), autoimmune disorders, early onset Parkinson’s disease and psychiatric disorders
- Karyotype using FISH, Multiplex ligation-dependent probe amplification assay (MLPA), or quantitative PCR (qPCR)
23
Q
Klinefelter Syndrome
Cause(s), Distinguishing Features, Associations, Variations, Diagnosis
A
- Male 47,XXY; due to meiotic nondisjunction
- Eunuchoid body shape, tall, long extremities, gynecomastia, high-pitched voice, female hair distribution and testicular atrophy (azoospermia)
- Autoimmune disorders, breast cancer, venous thromboembolic disease and osteoporosis
- 48,XXYY (Clinodactyly, Autism spectrum disorders, ADHD, anxiety and depression), 48,XXXY, 49,XXXXY, 47,XYY (this is not a variation 1:1000 boys and normal phenotype, but may be associated with severe acne, learning disability, autism spectrum disorders)
- Diagnosis
- Karyotype (Barr body)
- Decreased testosterone due to abnormal Leydig cell function —> increased LH —> increased estrogen
- Desgenesis of seminiferous tubules —> decreased inhibin B —> increased FSH
24
Q
Turner Syndrome
Cause(s), Distinguishing Features, Associations, Diagnosis
A
- Female 45,XO; due to meiotic nondisjunction or sometimes mitotic error (mosaicism 45,XO/46,XX), or Isochromosome (45,X(i))
- Short stature (if untreated), ovarian dysgenesis (streak ovary), shield chest, webbed neck and menopause before menarche (most common cause of primary amenorrhea) [pregnancy is possible in some cases (IVF, exogenous estradiol-17beta and progesterone)]
- Bicuspid aortic valve, preductal coarctation of aorta (femoral < brachial pulse), hydrops fetalis, cystic hygroma, lymphedema in feet and hands, and horse-shoe kidney, increased risk of gonadoblastoma (45,XO/46,XY)
- Diagnosis:
- Prenatal: U/S (cystic hygroma, heart defects and kidney abnormalities)
- Postnatal: karyotype (no Barr body)
- Decreased estrogen —> increased LH and FSH
25
Q
Triple X Syndrome (1:1000)
Cause(s), Distinguishing Features, Associations, Variations, Diagnosis
A
- 47,XXX; due to meiotic nondisjunction
- Phenotypically normal with normal fertility. Occasionally learning difficulties, decreased muscle tone, seizures, kidney problems and clinodactyly
- Anxiety and depression
- 48,XXXX (Tetrasomy X) [same as triple X syndrome but lower incidence], 49,XXXXX (Pentasomy X) [very rare, associated with short stature, severe intellectual disability and craniofacial abnormalities]
- Karyotype
26
Q
True Hermaphroditism (Ovotesticular disorder of sex development)
A
- 46,XX > 46,XY or 45,X/XY (mosaics) [genetic sex]
- Gonadal sex can be either an ovary on one side and a testis on the other or ovotestes
- Ductal sex is often mixed
- Phenotypic sex shows ambiguous genitalia
27
Q
Female Pseudohermaphroditism (46,XX DSD) (Cause(s), Presentation)
A
- Genetic sex is 46,XX
- Gonadal sex normal
- Ductal sex normal
- Phenotypic sex is abnormal due to ambiguous or virilized external genitalia
- Occurs with exposure of a female fetus to androgens in utero, by congenital adrenal hyperplasia (21 and 11); androgen-producing tumors (ovarian Sertoli-Leydig cell tumor) or exogenous androgens
- Also can occur in placental aromatase deficiency with inability to synthesize estrogens from androgens. Increased serum testosterone and androstenedione. Can present as maternal virilization during pregnancy (fetal androgens cross the placenta)
28
Q
Male Pseudohermaphroditism (46,XY DSD) (Cause(s), Presentation)
A
- Genetic sex is 46,XY
- Gonadal sex normal
- Ductal sex normal
- Phenotypic sex is abnormal with ambiguous or female genitalia
- Most common cause is Testicular feminization (complete androgen insensitivity syndrome) due to mutation of the androgen receptor (Xq11-12). Increased testosterone, estrogen and LH
- It presents either at puberty with amenorrhea and rudimentary vagina, but no uterus or ovaries and the testes are found usually in labia majora (needs surgical removal because of high risk of germ cell tumors like seminoma) or as a girl baby with inguinal hernia
- Other cause is 5alpha-reductase deficiency (AR) with inability to convert testosterone to DHT. Presents with ambiguous genitalia until puberty. Testosterone/estrogen levels are normal; LH is normal or increased
- Also 17alpha-hydroxylase deficiency (ambiguous genitalia and undescended testes)
29
Q
Kallmann Syndrome
Cause(s), Presentation
A
- X-linked recessive (KAL-1), AD (KAL-2), AD (KAl-3)
- Defective migration of GnRH cells and formation of olfactory bulbs
- Presents as failure to start or complete puberty (a form of hypogonadotropic hypogonadism) with anosmia or hyposmia with infertility
- Decreased GnRG, FSH, LH, testosterone (males) and estrogen (females)
30
Q
Phenylketonuria (PKU)
Mode of inheritance, Cause(s), Presentation, Association(s), Diagnosis, Treatment
A
- Autosomal recessive (1:10,000)
- Decreased phenylalanine hydroxylase or tetrahydrobiopterin cofactor (malignant PKU). Tyrosine becomes essential with excess phenylketons (phenylacetate, phenyllactate, phenylpyruvate) in urine
- Profound intellectual disability by 6 months of age, growth retardation, seizures, light-colored fair skin and hair, eczema, and musty (mousy) body odor
- Maternal PKU: lack of proper diet therapy during pregnancy. Finding in infant: microcephaly, intellectual disability, growth retardation and congenital heart defects
- Screening is done 2-3 days after birth (normal at birth because of maternal enzyme during fetal life)
- Rx: Decrease phenylalanine and increase tyrosine in diet, tetrahydrobiopterin supplementation, and avoidance of artificial sweeteners (aspartame)
31
Q
Alkaptonuria (Ochronosis)
Mode of inheritance, Cause(s), Presentation, Association(s)
A
- Autosomal recessive
- Congenital deficiency of homogentistic acid oxidase in the degradative pathway of tyrosine to fumarate leading to accumulation of homogentistic acid in tissues
- Bluish-black connective tissue and sclerae, cartilages (nose and ears), urine turns black on prolonged exposure to air
- Early onset degenerative arthritis
32
Q
Albinism
Mode of inheritance, Cause(s), Presentation, Association(s)
A
- Autosomal recessive
- Lack of the enzyme tyrosinase (copper-containing) that is needed for melanin production
- Deficiency of melanin pigment in skin, hair follicles, and eyes (occulocutaneous albinism)
- Increased risk of basal and squamous cell carcinoma
33
Q
Von Gierke disease
Mode of inheritance, Cause(s), Presentation, Diagnosis, Treatment
A
- Autosomal recessive; glycogen storage disease type I
- Deficiency of glucose-6-phosphatase which leads to impaired gluconeogenesis and glycogenolysis
- Severe fasting hypoglycemia, hepatomegaly, increased glycogen in liver, increased blood lactate, increased triglycerides and uric acid (gout)
- Liver biopsy and PAS stain (glycogen structure is normal)
- Rx: frequent oral glucose/cornstarch, avoidance of fructose and galactose
34
Q
Pompe disease
Mode of inheritance, Cause(s), Presentation, Diagnosis
A
- Autosomal recessive, glycogen storage disease type II
- Deficiency of lysosomal alpha-1,4-glucosidase (acid maltase)
- Hepatomegaly, skeletal muscle hypotonia with exercise intolerance, cardiomegaly and hypertrophic cardiomyopathy which leads to death by age of 2 years
- Biopsy with PAS stain (glycogen like-material in inclusion bodies)
35
Q
Cori disease
Mode of inheritance, Cause(s), Presentation, Diagnosis
A
- Autosomal recessive, glycogen storage disease type III
- Deficiency of debranching enzyme (alpha-1,6-glucosidase). Gluconeogenesis is intact
- Mild hypoglycemia and hepatomegaly
- Biopsy and PAS stain (short outer branches)
36
Q
Andersen disease (amylopectinosis) (Mode of inheritance, Cause(s), Presentation, Diagnosis)
A
- Autosomal recessive, glycogen storage disease type IV
- Deficiency of branching enzyme
- Infantile hypotonia, cirrhosis and death by 2 years
- Biopsy with PAS stain (very few branches, especially toward periphery
37
Q
McArdle disease
Mode of inheritance, Cause(s), Presentation, Diagnosis
A
- Autosomal recessive, glycogen storage disease type V
- Deficiency of skeletal muscle glycogen phosphorylase (myophosphorylase)
- Painful muscle cramps and myoglobinuria (red urine) with strenuous exercise, and arrhythmias from electrolyte abnormalities
- Biopsy with PAS stain (normal glycogen structure)
38
Q
Hers disease
Mode of inheritance, Cause(s), Presentation, Diagnosis
A
- X-linked recessive (and can be AR), glycogen storage disease type VI
- Deficiency of hepatic glycogen phosphorylase
- Mild fasting hypoglycemia, hepatomegaly and cirrhosis
- Biopsy and PAS stain (normal glycogen structure)
39
Q
Tay-Sachs disease
Mode of inheritance, Cause(s), Presentation, Diagnosis, Treatment
A
- Autosomal recessive, lysosomal storage disease
- Deficiency of hexoaminidase A (mutation of HEXA gene Chrom. 15) which will lead to accumulation of GM2 ganglioside in lysosomes of CNS and retina
- Ashkenazi Jews (1:30 carrier), normal children at birth, but by 6 months show onset of progressive mental deterioration and motor incoordination that progress to death by age 2-3 years. Cherry red spot on macula
- Dx:
- LM: dilated neurons with cytoplasmic vacuoles
- EM: distended lysosomes with whorled membranes (onion skin)
- Enzyme assay and DNA probes
- No Rx
40
Q
Niemann-Pick disease
Mode of inheritance, Cause(s), Presentation, Diagnosis, Treatment
A
- Autosomal recessive, lysosomal storage disease
- Deficiency of sphingomyelinase (Chrom. 11) which leads to accumulation of shpingomyelin in lysosomes of CNS and reticuloendothelial system
- Ashkenazi Jews, normal children at birth, but by 6 months onset of massive splenomegaly and lymphadenopathy, progressive mental and motor deterioration that progress to death by 2 years. Cherry red spot on macula
- Dx:
- LM: distended neurons with a foamy cytoplasmic vacuoles (lipid-laden macrophages)
- EM: distended lysosomes containing lamellated figures (“zebra bodies”)
- Enzyme assay and DNA probes
- No Rx
41
Q
Gaucher disease
Mode of inheritance, Cause(s), Presentation, Diagnosis, Treatment
A
- Autosomal recessive, most common lysosomal storage disease (99% is type I)
- Deficiency of glucocerebrosidase (beta-glucosidase) [Chrom. 1] which leads to accumulation of glucocerebroside in lysosomes of reticuloendothelial system
- Type I presents in adulthood with hepatosplenomegaly, thrombocytopenia/pancytopenia (secondary to hypersplenism), lymphadenopathy, osteoporosis, aseptic necrosis of femur and bone crisis. In type II and III there is also CNS manifestations
- Dx:
- LM: Gaucher cells (lipid-laden macrophages with fibrillary cytoplasm resembling crumpled tissue paper)
- Enzyme assay
- Rx: recombinant glucocerebrosidase
42
Q
Fabry disease
Mode of inheritance, Cause(s), Presentation, Diagnosis, Treatment
A
- X-linked recessive, lysosomal storage disease
- Deficiency of alpha-galactosidase A which leads to accumulation of ceramide trihexoside
- Early onset: triad of episodic peripheral neuropathy, angiokeratomas, and hypohidrosis. Late onset:progressive renal failure and cardiovascular disease (high blood pressure and restrictive cardiomyopathy)
- Dx: enzyme assay
- Rx: recombinant alpha-galactosidase A
43
Q
Krabbe disease
Mode of inheritance, Cause(s), Presentation, Diagnosis, Treatment
A
- Autosomal recessive, lysosomal storage disease
- Deficiency of galactocerebrosidase which leads to accumulation of galactocerebroside and psychosine
- Peripheral neuropathy, developmental delay, optic atrophy
- Dx: by LM: multinucleated “globoid cells” with nerve demyelination and degeneration
- Rx: bone marrow transplantation benefit cases if done early in the course of the disease
