Genetic disorders and inborn errors of metabolism Flashcards
1
Q
Malformation
A
Occurs when an intrinsically abnormal process forms abnormal tissue (e.g. bladder extrophy results from the failure of the infraumbilical mesenchyme to migrate and form the lower abdominal wall)
2
Q
Deformation
A
Occurs when mechanical forces exerted on normal tissue results in abnormal tissue (e.g. constraint caused by an abnormal shaped uterus results in an abnormally shaped fetal skull)
3
Q
Disruption
A
Occurs when normal tissue becomes abnormal after being subjected to destructive forces (e.g. decreased blood flow to an organ causes tissue ischemia, eventually resulting in atretic organ)
4
Q
Syndrome
A
Occurs when a collection of seemingly unrelated abnormal features occur in a familiar pattern (e.g. because many of the clinical features of children with Down syndrome, these children appear to be related to each other)
5
Q
Elevated alpha fetoprotein
A
- Fetal neural tube defects
- Mutiple gestation pregnancies
- Underestimated gestational age
- Ventral abdominal wall defects
- Fetal demise
- Fetal conditions that cause edema or skin defects
6
Q
Low alpha fetoprotein
A
- Overestimated gestational age
- Trisomies 21 and 18
- Intrauterine growth retardation
7
Q
Triple marker
A
AFP, unconjugated estriol, beta hCG
8
Q
Triple marker that suggests Down syndrome
A
- Low AFP
- Low unconjugated estriol
- High beta hCG
9
Q
Triple marker that suggests Trisomy 18
A
- Low AFP
- Low unconjugated estriol
- Low beta hCG
10
Q
Marfan syndrome
A
- Autosomal dominant
- Connective tissue disorder that affects primarily the ocular, cardiovascular, and skeletal systems
- Chromosome 15
- Fibrillin - protein that plays a major role in providing structure for connective tissues
11
Q
Clinical features of Marfan syndrome
A
- Skeletal: tall stature with elongated extremities and long fingers, joint laxity, chest wall deformities, scoliosis, kyphosis
- Ocular: upward lens subluxation, retinal detachment
- Cardiovascular: aortic root dilatation, mitral valve prolapse and aortic regurgitation
12
Q
Complications of Marfan syndrome
A
- Endocarditis
- Retinal detachment
- Sudden death as a result of aortic dissection
- Hypertension and chest trauma increase dissection risk (overall risk is reduced with beta blockers and avoiding contact sports)
13
Q
Prader-Willi syndrome
A
- Genomic imprinting
- Caused by the absence of a region not eh paternally derived chromosome 15
14
Q
Clinical features of Prader-Willi syndrome
A
- Craniofacial finidngs: almond shaped eyes and down turned, fishlike mouth
- Growth problems include failure to thrive because of feeding difficulties in first year followed by obesity as a result of hyperphagia later in childhood
- Short stature with small hands and feet
- Neurologic features: hypotonia, mental retardation, learning disabilities, and behavioral problems
- Hypogonadism manifests in small penis, small testes or cryptorchidism
15
Q
Complications of Prader-Willi syndrome
A
- Infancy: hypotonia may lead to poor sucking, feeding problems and developmental delay
- Childhood: obesity may lead to obstructive sleep apnea
- Adulthood: obesity may lead to cardiac disease and type 2 DM; psychiatric illness may also be present
16
Q
Angelman syndrome
A
- Happy puppet syndrome
- Characteristic jerky, puppetlike gait and happy demeanor with frequent laughter and smiling
- Genetic imprinting
- Deletion of a region on the maternally derived chromosome 15
17
Q
Clinical features of Angelman syndrome
A
- Neurologic: jerky arm movements, ataxia, and paroxysms of inappropriate laughter, mental retardation is severe
- Craniofacial findings include a small wide head, large mouth with widely spaced teeth, tongue protrusions and prognathia
- Blonde hair and pale blue deep set eyes
18
Q
Noonan syndrome
A
- Male version of Turner syndrome, but females may also be affected
- Usually sporadic, but AD pattern has been reported
- Chromosome 12
19
Q
Clinical features of Noonan syndrome
A
- Skeletal findings include short stature and a shield chest
- Craniofacial findings include a short webbed neck and low hairline, hypertelorism, epicentral skin folds, down slanting palpebral fissures and low set ears
- Cardiac defects include right sided heart lesions, most commonly pulmonary valve stenosis
- Mental retardation
20
Q
DiGeorge syndrome and velocardiofacial syndrome
A
- 2 distinct syndromes
- Both deletion at chromosome 22q11
CATCH-22:
- Cardiac anomaly
- Abnormal facies
- Thymic hypoplasia
- Cleft palate
- Hypocalcemia
- Gene defect on chromosome 22
21
Q
DiGeorge syndrome
A
Defect in the structures derived from the 3rd and 4th pharyngeal pouches
22
Q
Clinical features of DiGeorge syndrome
A
- Craniofacial findings include short palpebral fissures, small chin and ear anomalies
- Cardiac findings include aortic arch anomalies, ventricular septal defects and tetralogy of Fallot
- Thymus and parathyroid hypoplasia cause cell-mediated immunodeficiency and severe hypocalcemia
23
Q
Complications of DiGeorge syndrome
A
- Infections as a result of cell-mediated immunodeficiency
- Seizures caused by hypocalcemia
24
Q
Clinical features of velocardiofacial syndrome
A
- Craniofacial findings include cleft palate, wide prominent nose with a squared nasal root, short chin and fish shaped mouth
- Cardiac findings include ventricular septal defects and a right sided aortic arch
- Neurologic findings include neonatal hypotonia, learning diabilties and preservative behaviors
25
Ehlers-Danlos syndrome
- Production of defective type V collagen resulting in hyper extensible joints, fragile vessels, and loose skin
- Autosomal dominant
26
Clinical features of Ehlers-Danlos syndrome
- Musculoskeletal findings include hyperextensible joints with a tendency toward joint dislocation and scoliosis
- Dermatologic findings include soft, velvety textured, loose, fragile skin
- Minor lacerations result in large wounds that heal poorly with broad, atrophic, tissue paper-thin scars
- Cardiovascular findings include mitral valve prolapse, aortic root dilation, and fragile blood vessels that result in ease of bruising
- GI features include constipation, retail prolapse and hernias
27
Complications of Ehlers-Danlos syndrome
- Aortic dissection
| - GI bleeding as a result of vessel fragility
28
Osteogenesis imperfecta
- Results from mutations that cause production of abnormal type I collagen
- Classified into 4 types based on clinical, radiographic, and genetic criteria
29
Clinical features of osteogenesis imperfecta
- Blue sclerae
- Skeletal findings such as fragile bones resulting in frequent fractures, genu valgum (knock knees), scoliosis, or kyphosis, joint laxity, and osteoporosis or osteopenia
- Yellow or gray-blue teeth
- Easy bruisability
30
Complications of osteogenesis imperfecta
- Early conductive hearing loss
| - Skeletal deformities as a result of fractures
31
VACTERL association
- V: vertebral defects
- A: anal atresia
- C: cardiac anomalies (predominantly VSD)
- TE: tracheoesophageal fistula
- R: renal and genital defects
- L: limb defects, including radial hypoplasia, syndactyly, and polydactyly
32
CHARGE association
- C: colobomas (absence or defect of ocular tissue), usually of the retina; impaired vision is very common
- H: heart defects, most commonly tetralogy of Fallot
- A: atresia of the nasal choanae
- R: retardation of growth and cognition
- G: genital anomalies, including genital hypoplasia
- E: ear anomalies, including cup-shaped ears and hearing loss
33
Williams syndrome
- Most notable or the unique loquacious personality often described as a cocktail party personality
- Caused by deletion on chromosome 7 that includes the gene for elastin
- Inheritance autosomal dominant
34
Clinical features of Williams syndrome
- Elfin facies - with short palpebral fissures, flat nasal bridge, and round cheeks
- Mental retardation
- Loquacious personality
- Supravalvular aortic stenosis
- Idiopathic hypercalcemia in infancy
- Connective tissue abnormalities, including a hoarse voice and hernias
35
Clinical features of Cornelia de Lange syndrome
- Small for gestational age
- FTT
- Craniofacial findings include single eyebrow (synophrys), long, curly eyelashes, microcephaly, thin, turned down upper lip and mirognathia
- Infantile hypertonia
- Mental retardation
- Small hands and feet
- Cardiac defects
- Behavioral findings: autistic features, lack of facial expression and self destructive tendencies
36
Clinical features of Russell-Silver syndrome
- Small for gestational age
- Craniofacial findings include a small triangular face, prominent forehead and down turned mouth
- Because of the small face, the head appears large, but the head circumference is normal
- Skeletal findings include short stature and limb asymmetry
- Cafe au lait spots on the skin
- Excessive sweating
37
Clinical features of Pierre Robin syndrome
- Micrognathia
- Cleft lip and palate
- Large, protruding tongue
- Difficulty feeding because of cleft palate
38
Complications of Pierre Robin syndrome
Recurrent otitis media and upper airway obstruction that often requires tracheostomy
39
Clinical features of Cri du chat syndrome
- Slow growth
- Microcephaly
- Mental retardation
- Hypertelorism
- Downslanting palpebral fissures
- Catlike cry
40
Clinical features of trisomy 18
- Neurologic findings include mental retardation and hypertonia with scissoring of the lower extremities
- Delicate, small facial features
- Musculoskeletal findings include clenched hands with overlapping digits, dorsiflexed big toes and rocker bottom feet
41
Clinical features of trisomy 13
- Associated with midline defects, particularly of the face and forebrain
- Neurologic findings inclue holoprosencephaly, microcephaly, seizures and severe mental retardation
- Ocular findings include microphthalmia, retinal dysplasia, colobomas and a single eye
- Cleft lip and palate
42
Clinical features of Turner syndrome
- Short stature
- Webbed neck and low posterior hairline
- Shield chest with broadly spaced nipples and scoliosis and kyphosis
- Swelling of the dorsum of hands and feet (congenital lymphedema) may be present at birth
- Ovarian dysgenesis causes delayed puberty
- Cardiac defects usually include left sided heart lesions especially coarctation of the aorta, bicuspid aortic valve and hypoplastic left heart
- Hypothyroidism
43
Fragile X syndrome
- X linked disorder
- CGG repeats
- Most common inherited cause of mental retardation
44
Clinical features of fragile X syndrome
- Mild to severe mental retardation
- Craniofacial findings include large ears, macrocephaly, thickened nasal bridge and blue irides
- Large testes develop during puberty
- Behavioral findings include emotional instability, autistic features, and ADHD
45
Klinefelter syndrome
- Most common cause of male hypogonadism and infertility
- XXY genotype
- Risk increases with advancing maternal age
46
Clinical features of Klinefelter syndrome
- Tall stature with long extremities
- Hypogonadism, including small penis and testes, delayed puberty owing to lack of testosterone and infertility
- Gynecomastia
- Variable intelligence
- Behavioral findings include antisocial behavior and excessive shyness or aggression
47
Skeletal dysplasias
Group of inherited diseases characterized by short stature caused by bone growth abnormalities
48
Rhizomelia
Proximal long bone abnormalities (e.g. short humerus and femur)
49
Mesomelia
Medial long bone abnormalities (e.g. short ulna and tibia)
50
Acromelia
Distal bone abnormalities (e.g. small hands and feet)
51
Spndylodysplasia
Abnormalities of the spine with or without limb abnormalities
52
Achondroplasia
- Most common skeletal dysplasia
- Rhizomelia
- AD, but most are sporadic
- Fibroblast growth factor receptor 3 gene
- Increased incidence with advanced paternal age
53
Clinical features of achondroplasia
- Megalencephaly (large brain)
- Foramen magnum stenosis
- Frontal bossing
- Mid face hypoplasia
- Low nasal bridge
- Lumbar kyphosis in infancy evolving into lumbar lordosis in later childhood and adulthood
- Rhizomelic limb shortening, bowed legs and joint hyper extensibility
- Trident shaped hands
- Recurrent otitis media with conductive hearing loss
54
Complications of achondroplasia
- Foramen magnum stenosis may lead to hydrocephalus or cord compression
- Obstructive sleep apnea and respiratory compromise may occur from foramen magnum narrowing and upper airway obstruction
- Orthopedic problems such as severe bowed legs (genu varum) and back pain
55
Potter syndrome
- Caused by severe oligohydramnios
- This causes lung hypoplasia and fetal compression with limb abnormalities and facial features termed Potter facies
- Severe oligohydramnios may occur as the result of a chronic amniotic fluid leak or intrauterine renal failure caused by bilateral renal agencies, polycystic kidneys or obstructive uropathy
56
Amniotic band syndrome/ amnion rupture sequence
- Occurs as a result of rupture of the amniotic sac
- Fluid leak leads to intrauterine constraint and small strand from the amnion may wrap around the fetus, causing limb scarring and amputation
57
Fetal alcohol syndrome
- Alcohol is the most common teratogen
- Small for gestational age
- FTT
- Microcephaly
- Long smooth philtrum with a thin, smooth upper lip
- Mental retardation
- ADHD
- Cardiac defects (VSD is most common)
58
Fetal phenytoin syndrome
- Mild to moderate mental retardation
- Cardiac defects
- Growth retardation
- Nail and digit abnormalities
- Characteristic facial features
59
Alcohol associated anomalies
- Microcephaly
- Short palpebral fissures
- Long, smooth philtrum
- Variable mental retardation
60
Cigarette smoking associated anomalies
- Small for gestational age
| - Polycythemia
61
Cocaine associated anomalies
- Intrauterine growth retardation
- Microcephaly
- Genitourinary tract abnormalities
62
Diethylstilbestrol associated anomalies
- Increased risk of cervical carcinoma
| - Genitourinary anomalies
63
Isotretinoin associated anomalies
- CNS malformations
- Microtia
- Cardiac defects
- Thymic hypoplasia
64
Phenytoin associated anomalies
- Wide anterior fontanelle
- Thick hair with a low hair line
- Small nails
- Cardiac defects
65
Propylthiouracil associated anomalies
- Hypothyroidism
| - Goiter
66
Thalidomide associated anomalies
Phocomelia (malformed extremities resulting in flipperlike appendages)
67
Valproic acid associated anomalies
- Narrow head
- High forehead
- Midface hypoplasia
- Spina bifida
- Cardiac defects
- Convex nails
68
Warfarin associated anomalies
- Hypoplastic nose with a deep groove between the nasal ale and the nasal tip
- Stippling of the epiphyses
- Hypoplastic nails
69
Defects in amino acid metabolism
- Phenyketonuria
- Maple syrup urine disease
- Propionic acidemia
- Isovaleric acidemia
- Methylmalonic acidemia
- Transient tyrosinemia of the newborn
- Homocystinuria
- Alkaptonuria
- Ketotic hyperglycinemia
- Membrane transport defects: Hartnup's disease, cystinuria
70
Urea cycle disorders
- Transient hyperammonemia of the newborn
- Ornithine transcarbamylase deficiency
- Carbamyl phosphate synthetase deficiency
71
Disorders of metal metabolism
- Wilson's disease
- Hemochromatosis
- Menke's kinky hair disease
72
Lysosomal storage disease
Gangliosidoses:
- Tay-Sachs disease
- Gaucher's disease
- Nieman-Pick disease
- Metachromatic leukodystrophy
- Krabbe disease
- Fabry disease
- Farber disease
Mycopolysacharidoses:
- Hurler syndrome
- Hunter syndrome
- Sanfilippo syndrome
- Morquio syndrome
73
Defects in fatty acid oxidation
- Medium chain acyl-CoA dehydrogenase deficiency
- Long chain acyl-CoA dehydrogenase deficiency
- Short chain acyl-CoA dehydrogenase deficiency
- Carnitine palmitoyl transferase deficiency
74
Defects in carbohydrate metabolism
- Galactosemia
- Hereditary fructose intolerance
- Glycogen storage disease: type 1 (von gierke's disease), type 2 (pompe's disease)
75
Mitochondrial disorders
- Kearn-Sayre's syndrome
- MERRF
- MELAS
76
Defects in heme pigment biosynthesis
- Acute intermittent porphyria
- Erythropoietic porphyria
- Porphyria cutanea tarda
- Hereditary coproporphyria
77
Mousey/musty odor
Phenylketonuria
78
Sweet maple syrup odor
Maple syrup urine disease
79
Sweaty feet odor
Isovaleric or glutaric acidemia
80
Rotten cabbage odor
Hereditary tyrosinemia
81
Hypoglycemia with ketosis
- Organic academy
| - Carbohydrate disease
82
Serum NH3 greater than 200 mM
Urea cycle defects
83
Elevated NH3 and metabolic acidosis
Organic acidemias
84
Urinary ketones
Alway abnormal in a newborn
85
Corrects acidosis
Sodium bicarbonate
86
Increases ammonia excretion
Sodium benzoate and sodium phenylacetate
87
Prevent bacterial production of ammonia in the colon
Oral neosporin and lactulose
88
Rule out hypoglycemia
Serum glucose
89
Rule out hypocalcemia, hypermagnesemia, or hypomagnesemia
Serum Ca and Mg
90
Assess for anemia, neutropenia, thrombocytopenia
CBC with differential
91
Assess for ketones
Urinalysis
- Presence of ketones is esp suspicious in newborns because normally they do not produce ketones well
- In older children, absence of ketones with hypoglycemia is suspicious for fatty acid oxidation defect
92
Assess for anion gap metabolic acidosis
Arterial blood gas and serum electrolytes
93
Urine-reducing substance
- If positive, dipstick for glucose
| - Non-glucose reducing substance is suggestive of galactosemia
94
Rule out lactic academies or organic acidemias in presence of metabolic acidosis
Serum lactate and pyruvate
95
Rule out aminoacidemia or organic academies in presence of metabolic acidosis
Plasma amino acids
96
Increased ammonia with elevated plasma amino acids
Suspect aminoacidemias
97
Increased ammonia with elevated urine organic acids
Suspect ornithine transcarbamylase
98
Homocystinuria
- Cystathione synthase deficiency
| - AR
99
Clinical features of homocystinuria
- Marfanoid body habitus without arachnodactyly
- Downward lens subluxation (in Marfan syndrome, lens subluxation is upward)
- Hypercoagulable state increases risk of stroke, myocardial infarction and deep vein thrombosis
- Cardiovascular abnormalities include mitral or aortic regurgitation
- Aortic dilatation is absent (in contrast to Marfan syndrome)
- Scoliosis and large stiff joints
- Developmental delay, mild mental retardation and psychiatric illness
100
Diagnosis of homocystinuria
- Increased methionine in urine and plasma
| - Positive urinary cyanide nitroprusside test
101
Management of homocystinuria
- Methionine restricted diet
- Aspirin to decrease risk of thromboembolism
- Folic acid and vitamin B6 supplementation
102
Transient tyrosinemia of the newborn
Occurs in premature infants who receive high protein diets
103
Clinical features of transient tyrosinemia of the newborn
Begin during the first 2 weeks of life and may include poor feeding and lethargy. May also be asymptomatic.
104
Diagnosis of transient tyrosinemia of the newborn
Elevated tyrosine and phenylalanine
105
Management of transient tyrosinemia of the newborn
- Decreasing protein intake during acute episode
| - Vitamin C may help eliminate tyrosine
106
Cystinuria
- AR
- Defect in renal reabsorption of cystine, lysine, arginine and ornithine
- Leads to renal stones
- Clinical features: UTIs, dysuria, abdominal or back pain, urgency, polyuria
107
Hartnup disease
- AR
- Defect in transport of neutral amino acids
- Most patients are asymptomatic
- Clinical features: intermittent ataxia, photosensitive rash, mental retardation, and emotional lability
108
Transiet hyperammonemia of the newborn
- Self limited
- May present in premature infants within the initial 24-48 hours of life
- Symptoms are non-specific
- Clinical features: respiratory distress, alkalosis, vomiting, and lethargy rapidly progressing to coma
109
Ornithine transcarbamylase deficiency
- Most common urea cycle defect
| - X linked recessive
110
Clinical features of ornithine transcarbamylase deficiency
- Begin at onset of protein ingestion
- Vomiting and lethargy leading to coma
- Some females with mild disease may present in childhood with cyclic vomiting and intermittent ataxia
111
Diagnosis of ornithine transcarbamylase deficiency
- Elevated urine orotic acid
- Decreased serum citrulline
- Increased ornithine
- Liver biopsy
112
Management of ornithine transcarbamylase deficiency
- Low protein diet
- Management of hyperammonemia
- Liver transplant may be necessary
113
Clinical features of phenylketonuria
- Developmental delay
- Infantile hypotonia
- Mousy or musty odor
- Progressive mental retardation
- Eczema
- Decreased pigment (light eyes and hair)
- Mild PKU may present in early childhood with developmental delay, hyperactivity
114
Diagnosis of phenylketonuria
Increased phenylalanine to tyrosine ratio in serum
115
Management of phenylketonuria
Phenylalanine restricted diet
116
Clinical features of maple syrup urine disease
- Progressive vomiting and poor feeding
- Lethargy, hypotonia, and coma
- Developmental delay
- Maple syrup odor in urine
- Hypoglycemia and severe acidosis during episodes
117
Diagnosis of maple syrup urine disease
Increased serum and urine branched chain amino acids
118
Management of maple syrup urine disease
Dietary protein restriction
119
Clinical features of tyrosinemia type I
- Episodes of peripheral neuropathy
- Chronic liver disease
- Odor of rotten fish or cabbage odor
- Renal tubular dysfunction
120
Diagnosis of tyrosinemia type I
Succinylacetone in urine
121
Management of tyrosinemia type I
Dietary restriction of phenylalanine, tyrosine and NTBC
122
Galactosemia
- AR
- Galactose-1-phosphate uridyltransferase deficiency
- Suspected in any newborn with hepatomegaly and hypoglycemia
123
Clinical features of galactosemia
- Begin after the newborn feeds a cow's milk based formula or breastfeeds for the first time (both cow's milk and breast milk contain galactose)
- Vomiting, diarrhea, FTT
- Hepatic dysfunction with hepatomegaly
- Cataracts with a characteristic oil droplet appearance
- Renal tubular acidosis
124
Diagnosis of galactosemia
- Nonglucose-reducing substance in urine
- Confirmation of enzyme deficiency in RBCs
- Prenatal and newborn screening are available
125
Management of galactosemia
Galactose free diet, such as soy or elemental formulas
126
Complications of galactosemia
- Mental retardation if diagnosis is delayed
- Nearly all females suffer from ovarian failure
- Death in early infancy, typically from E coli sepsis, is common if the diagnosis is not suspected and treated
127
Hereditary fructose intolerance
- Fructose-1-phosphate aldolase B deficiency
- Begins after introduction of fruit or fruit juice
- Clinical features: severe hypoglycemia, vomiting, diarrhea, FTT, seizures
- Management includes avoidance of fructose, sucrose and sorbitol
128
Von Gierke's disease
- Glucose-6-phosphatase deficiency
- Clinical features: persistent hypoglycemia, hepatomegaly, metabolic acidosis, hypertriglyceridemia and enlarged kidneys
- Management includes frequent feeding with high complex carb diet
- Patients are at risk for hepatocellular carcinoma
129
Pompe's disease
- Alpha glucosidase deficiency
- Should be suspected in any infant with muscular weakness and cardiomegaly
- Present within first 2 weeks with flaccid weakness, poor feeding, progressive cardiomegaly, hepatomegaly and acidosis
130
Nonketotic hypoglycemia, hyperammonemia, myopathy and cardiomyopathy
Fatty acid oxidation defect
131
Kearns-Sayre syndrome
- Ophthalmoplegia
- Pigmentary degeneration of the retina
- Hearing loss
- Heart block
- Neurologic degeneration
132
MELAS
Mitochondrial Encephalopathy, Lactic Acidosis and Stroke like episodes
133
Tay-Sachs disease
Hexosaminidase A deficiency
134
Clinical features of Tay-Sachs disease
Infantile onset TS disease:
- Presents early in infancy
- Decreasing eye contact
- Hypotonia
- Mild motor weakness
- Increased startle as a result of hyperacusis (increased sensitivity to sound)
- Macrocephaly
- Cherry red macula
- Progressive blindness, seizures, and severe developmental delay
Juvenile or adult onset TS disease:
- After 2 year
- Ataxia
- Dysarthria
- Choreoathetosis
- Cherry red macula is absent
135
Diagnosis of Tay-Sachs disease
Decreased hexosaminidase A activity in leukocytes or fibroblasts
136
Gaucher's disease
- Glucocerebrosidase deficiency
- Most common gangliosidosis
- Clinical features: hepatosplenomegaly, thrombocytopenia, Erlenmeyer flask-shape to distal femur
137
Niemann-Pick disease
- Sphingomyelinase deficiency
| - Clinical features: neurodegeneration, ataxia, seizures, hepatosplenomegaly, cherry red macula
138
Metachromatic leukodystrophy
- Arylsulfatase A deficiency
| - Clinical features: ataxia, seizures, and progressive mental retardation
139
Dysostosis multiplex
- Associated with mucopolysaccharidoses
- Constellation of bony abnormalities that include a thickened cranium
- J shaped sella turcica
- Malformed, ovoid or beaklike vertebrae
- Short and thickened clavicles
- Oar shaped ribs
140
Hurler syndrome
- Alpha-L-iduronidase deficiency
| - Most severe mucopolysaccharidosis
141
Clinical features of Hurler syndrome
- Begin after 1 year
- Developmental delay
- Hepatosplenomegaly
- Kyphosis
- Progressively coarsened facial features
- Frontal bossing
- Prominent safittal and metopic sutures
- Wide nasal bridge
- Thickening of the nasopharyngeal tissues
- Hydrocephalus
- Corneal clouding
- Progressively stiff and contracted joints
142
Diagnosis of Hurler syndrome
Finding dermatan and heparan sulfate in the urine and decreased alpha-L-iduronidase enzyme activity in leukocytes or fibroblasts
143
Hunter syndrome
Inherited X linked recessive
144
Clinical features of Hunter syndrome
- Hepatosplenomegaly
- Hearing loss
- Progressively stiff and contracted joints
- Small papillose over shoulder, scapula and lower back
- Dysostosis multiplex
- NO corneal clouding
145
Diagnosis of Hunter syndrome
Finding dermatan and heparan sulfate in the urine and decreased alpha-L-iduronidase enzyme activity in leukocytes or fibroblasts
146
Sanfilippo syndrome
Characterized by rapid and severe mental and motor retardation
147
Morquio syndrome
- Differs from other mucopolysaccharidoses in that mental retardation is ABSENT
- Severe scoliosis leading to cor pulmonale results in death
148
Diagnosis of porphyrias
Increased serum and urine porphobilinogen
149
Management of porphyrias
- IV glucose
- Correction of electrolyte abnormalities
- Avoidance of fasting and precipitating drugs
150
Wilson's disease
- AKA hepatolenticular degeneration
| - Defect in copper excretion that causes copper deposition initially in the liver, followed by the brain, eyes and heart
151
Clinical features of Wilson's disease
- Keyser-Fleischer rings in the peripheral cornea (deposition in Descemet's membrane)
- Ataxia
- Seizures
- Behavioral changes
- Dystonia
- Dysarthria
- Tremors
152
Diagnosis of Wilson's disease
- Decreased serum ceruloplasmin is the most commonly used screening test
- Elevated serum and urine copper
- Copper deposition in hepatocytes obtained by liver biopsy
153
Management of Wilson's disease
- Avoid copper containing food (e.g. nuts, liver, shellfish, and chocolate)
- Chelation therapy with penicillamine and zinc salts to prevent absorption
- Liver transplant
154
Menkes kinky-hair disease
- X linked recessive
- Abnormal copper transport
- LOW serum copper (this is high in Wilson's disease)
- Clinical features: myoclonic seizures, pale kinky friable hair, optic nerve atrophy, severe mental retardation, progressive neurologic degeneration and early death
- Diagnosis: typical hair findings, low serum ceruloplasmin, low serum copper
