Chapter 5 - Inborn Errors Flashcards
1
Q
How do X-linked dominant disorders differ between males and females who inherit them?
A
such disorders tend to be more severe or lethal in males
2
Q
Which classic inheritance pattern tends to only affect males?
A
X-linked recessive
3
Q
Describe the inheritance of Angelman and Prader-Willi syndrome?
A
- both are due to genomic imprinting
- in the case of Angelman syndrome, the paternal allele is imprinted and silent; the maternal allele is either abnormal or there is paternal disomy
- in the case of Prader-Willi syndrome, the maternal allele is imprinted and silent; the paternal allele is either abnormal or there is maternal disomy
4
Q
What is the difference between a malformation, deformation, and disruption?
A
- malformation: an intrinsically abnormal process forms abnormal tissue
- deformation: mechanical forces exerted on normal tissue result in abnormal tissue
- disruption: normal tissue becomes abnormal after being subjected to destructive forces such as decreased blood flow
5
Q
Ultrasound is used in the prenatal period to asses what?
A
gestational age, fetal growth, and major anomalies
6
Q
Elevated maternal serum AFP is a marker for what seven items?
A
- neural tube defects
- multiple gestation pregnancies
- underestimated gestational age
- ventral abdominal wall defects
- fetal demise
- conditions causing edema
- skin defects
7
Q
Low maternal serum AFP is a marker for what three items?
A
- overestimated gestational age
- trisomy 18 or 21
- intrauterine growth retardation
8
Q
What do we mean by the term “triple marker”?
A
a term which refers to maternal serum AFP, unconjugated estriol, and B-hCG which are used as non-invasive methods for assessing the fetus for trisomy syndromes
9
Q
What triple marker profiles are consistent with trisomy 18 or trisomy 21?
A
- AFP, estriol, and B-hCG are all low in trisomy 18
- AFP and estriol are low but B-hCG is high in trisomy 21
10
Q
What is chorionic villus sampling? When is it done during the gestational period? What is it used for?
A
- it is a collection of virus tissue from the chorion of the trophoblast
- done at 10-13 weeks gestation
- used for karyotyping, DNA extraction, and enzyme analyses
11
Q
What is amniocentesis? When is it done during the gestational period? What is it used for?
A
- it is a collection of amniotic fluid which contains sloughed fetal cells
- done at 16-18 weeks gestation
- used for karyotyping, DNA extraction, and enzyme analyses
12
Q
What is percutaneous umbilical blood sampling? What is it used for?
A
- it is a collection of fetal blood
- used to assess for hematologic abnormalities, genetic disorders, infections, and fetal acidosis
- can also be used to administer medications or blood transfusions for the fetus
13
Q
What is the difference between chorionic villus sampling and amniocentesis?
A
- CVS is done earlier at 10-13 weeks compared to amniocentesis at 16-18
- CVS is a collection of chorion tissue whereas amniocentesis is a collection of sloughed fetal cells
- both are used for the same analytic purposes
14
Q
Marfan Syndrome
A
- an autosomal dominant connective tissue disorder with primarily ocular, cardiovascular, and skeletal problems
- due to a mutation of the fibrillin gene on chromosome 15, which codes for an elastin scaffold
- skeletal findings include tall stature, elongated extremities and fingers, joint laxity, pectus excavatum, scoliosis or kyphosis, and a decreased upper-to-lower segment ratio (symphysis pubis is the divider)
- ocular findings include upward lens subluxation and retinal detachment
- cardiovascular findings include aortic root dilatation, aortic dissection, mitral valve prolapse, and aortic regurg
- it is a clinical diagnosis but may be confused with homocystinuria, which shares many features
- complicated by endocarditis, retinal detachment, and aortic dissection resulting in sudden cardiac death; hypertension and trauma both increase risk of dissection
- manage with beta-blockers, avoidance of contact sports, endocarditis prophylaxis, and regular eye exams
15
Q
Prader-Willi Syndrome
A
- a condition arising from the absence of a normal region of the paternally-derived chromosome 15 since the maternal copy is imprinted and silenced
- FISH detects the deletion in almost all patients
- hypotonia leads to poor sucking and feeding problems, causing failure to thrive in the first year of life, then hyperplagia leads to obesity later in childhood
- appearance includes almond-shaped eyes and a fishlike mouth, short stature, and obesity
- often present with mental retardation and hypogonadism
- complications arise from obesity and include obstructive sleep apnea, cardiac disease, and type II diabetes
16
Q
Angelman Syndrome
A
- a condition arising from the absence of a normal region of the maternally-derived chromosome 15 since the paternal copy is imprinted and silenced
- symptoms include paroxysms of inappropriate laughter, a happy demeanor, severe mental retardation with speech delay, and ataxia with jerky arm movements
- appearance includes a small wide head, large mouth, widely spaced teeth, tongue protrusion, prognathia, and blond hair with deep-set blue eyes
- diagnosed using FISH
17
Q
Noonan Syndrome
A
- often described as the male version of Turner syndrome though it can be found in females
- inheritance is typically sporadic, occasionally AD, and mapped to chromosome 12
- presents with short stature, shield chest, webbed neck, low hairline, hypertelorism (widely spaced eyes), epicentral skin folds, downslanting palpebral fissures, low-set ears
- in contrast to Turner syndrome, heart lesions are mostly right-sided and pulmonary valve stenosis is most common
18
Q
DiGeorge Syndrome
A
- a defect in the structures derived from the third and fourth pharyngeal pouches due to a chromosome 22q11 deletion
- CATCH: cardiac anomalies (aortic arch anomalies, VSD, and Tetralogy of Fallot), abnormal facies (short palpebral fissures, small chin, ear anomalies), thymus hypoplasia (cell-mediated immunodeficiency and infection), cleft palate, hypocalcemia (complicated by seizures)
- inheritance can be sporadic or autosomal dominant
- diagnosis is made via FISH probes
19
Q
Velocardiofacial Syndrome
A
- a syndrome related to but separate from DiGeorge and also due to a chromosome 22 deletion
- craniofacial findings include cleft palate, wide prominent nose, squared nasal root, short chin, and fish-shaped mouth
- cardiac findings are VSD and right-sided aortic arch
- neurologic findings include hypotonia, learning disability, and perseverative behaviors
- diagnosed via FISH probes
20
Q
Ehlers-Danlos Syndrome
A
- a condition caused by defective type V collagen
- inheritance is autosomal dominant
- presents with hyperextensible joints with dislocation and scoliosis; fragile skin such that minor lacs result in large wounds with tissue paper-thin scars; ease of bruising, mitral valve prolapse, and aortic root dilatation; and constipation, rectal prolapse, and hernias
- major complications are GI bleeding and aortic dissection
21
Q
Osteogenesis Imperfecta
A
- a condition resulting from abnormal type I collagen
- presents with blue sclera, yellow or gray-blue teeth, and easy bruisability
- fragile bones result in frequent fractures, genu valgum (aka knock-knees), scoliosis or kyphosis, joint laxity, and early conductive hearing loss
22
Q
VACTERL Association
A
a group of sporadic, mesoderm malformations
- Vertebral defects
- Anal atresia
- Cardiac anomalies (VSD)
- TE
- Renal anomalies and genital defects
- Limb defects including radial hypoplasia, syndactyly, and polydactyly
23
Q
CHARGE Association
A
a group of sporadic malformations
- Colobomas, most often of the retina, and impaired vision
- Heart defects, usually Tetralogy of Fallot
- Atresia fo the nasal choanae
- Retardation of growth and cognition
- Genital anomalies
- Ear anomalies, namely cup-shaped ears and hearing loss
24
Q
Williams Syndrome
A
- a condition caused by a deletion on chromosome 7 involving the elastin gene
- inheritance is autosomal dominant
- presents with elfin facies, mental retardation, and loquacious personality
- as well as supravalvular aortic stenosis, idiopathic hypercalcemia, and connective tissue abnormalities, leading to hoarse voice and hernias
25
Cornelia de Lange
- a syndrome notable for a single eyebrow and very short stature without skeletal abnormalities
- symptoms include small for gestational age, failure to thrive, infantile hypertonia, microcephaly with mental retardation, small hands and feet, and cardiac defects
- behavioral signs include autistic features, lack of facial expression, and self-destructive tendencies
26
Russell-Silver Syndrome
- known for the features of short stature, skeletal asymmetry, and normal head circumference
- other features include small for gestational age, a small triangular face which may make the head appear large despite the normal circumference, limb asymmetry, cafe-au-lait spots, and excessive sweating
27
Pierre Robin Syndrome
- a sequence of micrognathia, cleft lip/palate, and large protruding tongue
- often complicated by recurrent otitis media and upper airway obstruction frequently requiring tracheostomy
28
Cri-du-chat Syndrome
- one caused by a partial deletion the short arm of chromosome 5
- presents with slow growth, microcephaly with mental retardation, hypertelorism, and a characteristic cat-like or high-pitched cry
29
Trisomy 21
- the most common trisomy (1:660 live births) with risk primarily tied to maternal age which increases the occurrence of nondisjunction within the ovum
- clinical features include craniofacial abnormalities, hypotonia, mental retardation, MSK abnormalities, GI abnormalities, and cardiac defects
- craniofacial findings include upward slanting palpebral fissures, brushfield spots, and protruding tongue
- MSK abnormalities include clinodactyly, single palmar crease, and widely spaced first and second toes
- GI abnormalities include duodenal atresia, Hirschsprung's, omphalocele, and pyloric stenosis
- the most common cardiac finding is an endocardial cushion defect
- complicated by atlantoaxial cervical spine instability, leukemia, celiac disease, early onset Alzheimer's, obstructive sleep apnea, conductive hearing loss, hypothyroidism, and cataracts/glaucoma/refractive errors
30
Describe the complications of trisomy 21 and how they are managed as pediatric patients.
- atlantoaxial cervical spine instability requires flexion-extension cervical spine radiographs by 3-5 years of age
- celiac disease requires a total IgA and IgA anti-endomysium antibody screening at 2 years of age
- conductive hearing loss necessitates hearing tests every 1-2 years
- hypothyroidism requires annual TSH screening
- risk for cataracts, glaucoma, and refractive errors requires annual ophthalmologic exams
- leukemia, early onset Alzheimer's, obstructive sleep apnea are also common
31
Trisomy 18
- the second most common trisomy and more common in females
- neurologic findings include mental retardation and hypertonia with scissoring of the lower extremities
- delicate, small facial features
- clenched hands with overlapping digits, dorsiflexed big toes, and rocker bottom feet
- most die within the first year of life
32
Trisomy 13
- a trisomy associated with midline defects
- neurologic findings include holoprosencephaly, microcephaly, seizures, and severe mental retardation
- ocular findings include microphthalmia, retinal dysplasia, and colobomas
- cleft lip and palate are common
- death is usually within the first month of life
33
Turner Syndrome
- a phenotype associated with the XO genotype in women
- appearance includes short stature, webbed neck, shield chest, and scoliosis or kyphosis
- congenital lymphedema leads to swelling of the dorsal of the hands and feet
- ovarian dysgenesis results in streak ovaries and causes pubertal delay
- cardiac defects are usually left-sided and include coarctation of the aorta, bicuspid aortic valve, and hypoplastic left heart
34
Klinefelter Syndrome
- an XXY genotype in males
- the most common cause of male hypogonadism and infertility; it is seen in 1:500 live male births and risk increases with maternal age
- have tall stature, long extremities, gynecomastia, and variable intelligence
- hypogonadism leads to delayed puberty and infertility
- behavioral findings include antisocial behavior and excessive shyness or aggression
35
Fragile X Syndrome
- an X-linked disorder arising from a variable number of CGG repeats that demonstrate anticipation
- typically more severe in males but females may demonstrate some intellectual disability
- presents with mild to severe mental retardation as well as emotional instability, autistic features, and ADHD
- craniofacial findings include large ears, macrocephaly, and a thickened nasal bridge
- large testes develop during puberty
36
Define rhizomelia.
a classification for skeletal dysplasia defined by proximal long bone abnormalities
37
Define mesomelia.
a classification for skeletal dysplasia defined by medial long bone abnormalities
38
Define acromelia.
a classification for skeletal dysplasia defined by distal abnormalities such as small hands or feet
39
Define spondylodysplasia.
a classification for skeletal dysplasia that involves the spine, with or without limb abnormalities
40
Achondroplasia
- a rhizomelic skeletal dysplasia caused by a gain of function mutation involving FGFR3
- autosomal dominant but most cases are sporadic and incidence increase with advancing paternal age
- presentation includes megalencephaly, foramen magnum stenosis, lumbar kyphosis as an infant progressing to lumbar lordosis in later childhood, rhizomelic limb shortening, and trident-shaped hands
- may be complicated by recurrent otitis media with conductive hearing loss, obstructive sleep apnea and respiratory compromise secondary to foramen magnum narrowing, and severe bowed legs or back pain
- foramen magnum stenosis may lead to hydrocephalus or cord compression, often indicated by head sweating and dilated facial veins in the early stages
41
What is Potter sequence?
a syndrome of lung hypoplasia, limb abnormalities, and Potter facies that arises as a result of severe oligohydramnios from either chronic amniotic fluid leak or intrauterine renal failure
42
Amniotic Band Syndrome
- there is a rupture of the amniotic sac and fluid leaks, leading to intrauterine constraint
- at the same time, small strands form the amnion may wrap around the fetus, causing limb scarring and amputation
43
What are the features of fetal alcohol syndrome?
- mental retardation, ADHD
- small-for-gestational age, failure to thrive, and microcephaly
- a long, smooth philtrum with a thin, smooth upper lip
- cardiac defects, namely VSD
44
What is the most common teratogen?
alcohol
45
What are the features of fetal phenytoin syndrome?
- mild to moderate retardation
- cardiac defects
- growth retardation with nail and digit abnormalities as well as thick hair with a low hairline
- a wide anterior fontanelle
46
In utero exposure to cigarette smoke is most often associated with what anomalies?
small for gestational age and polycythemia
47
In utero exposure to cocaine is most often associated with what anomalies?
- intrauterine growth retardation
- microcephaly
- GU tract abnormalities
48
In utero exposure to DES is most often associated with what?
a heightened risk for cervical carcinoma
49
In utero exposure to isotretinoin is most often associated with what anomalies?
- CNS malformations
- microbial
- cardiac defects
- thymus hypoplasia
50
In utero exposure to PTU is most often associated with what anomalies?
hypothyroidism and goiter
51
In utero exposure to thalidomide is most often associated with what anomalies?
phocomelia (malformed extremities resulting in flipper-like appendages
52
In utero exposure to valproate is most often associated with what anomalies?
- narrow head, high forehead, mid face hypoplasia, and convex nails
- spina bifida
- cardiac defects
53
In utero exposure to warfarin is most often associated with what anomalies?
- hypoplastic nose with a deep groove between the nasal aloe and the nasal tip
- stippling of the epiphyses
- hypoplastic nails
54
What is the most common congenital anomaly of the CNS?
neural tube defects
55
What dosage of folic acid is recommended to prevent neural tube defects?
400-800 ug/day
56
What is the risk for congenital heart disease?
approximately 1% in the general population with the recurrence risk increasing with each affected child
57
What is the combined incidence of inborn errors of metabolism?
1 in 5,000 live births
58
Most inborn errors of metabolism have what inheritance pattern? What is second most common?
autosomal recessive is most common; however, some are X-linked recessive
59
What might make you suspicious that a child has an inborn error of metabolism?
- unexplained seizures, developmental delay, progressive neurologic deterioration, persistent or recurrent vomiting, or failure to thrive
- family history of neonatal deaths in siblings or affected males on the maternal side, parental consanguinity, mental retardation, or unusual dietary preferences in relatives
60
Inborn errors of metabolism may resemble what other, more common illness?
sepsis
61
What is the clinical significant of vomiting with metabolic acidosis and why?
vomiting is expected to cause a metabolic alkalosis, so when it is seen in with acidosis, it is an indicator of an inborn error of metabolism
62
Describe the two initial labs used in the evaluation of a newborn for an inborn error of metabolism?
- the initial lab evaluation includes assessment for metabolic acidosis and elevated serum ammonia; these results guide further evaluation
- if acidosis is present get a serum lactate and pyruvate as well as a plasma amino acids to rule out lactic academies or organic anemias
- if increased ammonia is present, get a plasma amino acids (if elevated, suspect aminoacidemias) or urine organic acids (if elevated, suspect orotic acid or ornithine transcarbamylase deficiency)
63
How is acidosis correct in newborns with inborn errors of metabolism?
sodium bicarbonate
64
How is hyperammonemia treated medically?
- sodium benzoate and sodium phenyl acetate increase ammonia excretion
- lactulose acidifies the GI tract and traps NH4 for excretion
- oral neosporin kills ammoniogenic bacteria in the colon
65
Homocystinuria
- an autosomal recessive cystathionine synthase deficiency with features similar to Marfan syndrome
- presents with marfanoid habitus absent arachnodactyly, downward lens subluxation, hyper coagulable state, cardiovascular abnormalities such as mitral or aortic regurgitation, scoliosis, and developmental delay
- in contrast to Marfan syndrome, there is no arachnodactyly, no upward lens subluxation, and no aortic dilatation
- diagnosed based on elevated methionine in urine and plasma or a positive urinary cyanide nitroprusside test
- manage with a methionine-restricted diet, aspirin, folic acid, and vitamin B6 supplementation
66
Transient Tyrosinemia of the Newborn
- a self-limiting disease seen in premature infants who receive high-protein diets
- begins in the first two weeks of life with poor feeding or lethargy
- diagnosed based on elevated serum tyrosine and phenylalanine
- manage by restricting protein intake and supplementing vitamin C to eliminate tyrosine
67
Phenlketonuria
- an autosomal recessive inborn error of metabolism
- presents with progressive mental retardation, hypotonia, a musty body odor, eczema, and decreased pigmentation
- in some mild cases, it may not present until early childhood with developmental delay and hyperactivity
- diagnosed based on elevated phenylalanine/tyrosine ratio
- can be managed with a phenylalanine restriction and if this is initiated within one month of age, near-normal intelligence can be expected
68
Maple Syrup Urine Disease
- an autosomal recessive inborn error of metabolsim
- presents with progressive vomiting and poor feeding, lethargy, hypotonia, developmental delay, maple syrup-scented urine, and hypoglycemia with severe acidosis
- diagnosed with elevated serum and urine branched-chain amino acids
- dietary protein restriction within 2 weeks of life may prevent neurologic damage
69
Tyrosinemia Type I
- an autosomal recessive inborn error of metabolism
- presents with episodes of peripheral neuropathy, chronic liver disease, an odor of rotten-fish or cabbage, and renal tubular dysfunction
- diagnosed based on succinylacetone in urine
- managed with dietary restriction of phenylalanine, tyrosine, and NTBC; liver transplant may eventually be required
- death will occur within one year if onset is in infancy; otherwise, there is an increased risk for HCC and cirrhosis
70
Cystinuria
- an autosomal recessive membrane transport defect that impairs renal reabsorption of cystine, lysine, arginine, and ornithine
- contributes to the formation of cystine nephrolithiasis with possible UTI, dysuria, back pain, urgency, and urinary frequency
71
Hartnup Disease
- an autosomal recessive membrane transport defect affecting neutral amino acids
- most cases are asymptomatic but may present with intermittent ataxia, photosensitive rash, mental retardation, and emotional liability
72
Transient Hyperammonemia of the Newborn
- a self-limited disorder seen in premature infants within the first 1-2 days of life
- symptoms include respiratory distress, alkalosis, vomiting, and lethargy progressing to coma
- treatment of hyperammonemia with lactulose, oral neosporin, etc. is required to prevent long-term neurologic dysfunction
73
Ornithine Transcarbamylase Deficiency
- an X-linked recessive and the most common urea cycle defect
- symptoms begin at the onset of protein ingestion with vomiting and lethargy progressing to coma
- diagnosed based on elevated urine orotic acid, decreased serum citrulline, and increased ornithine
- manage with a low-protein diet and treatment of hyperammonemia
74
Galactosemia
- an autosomal recessive galactose-1-phosphate uridyltransferase deficiency
- should be considered in any newborn with hepatomegaly and hypoglycemia
- presents after ingestion of milk with vomiting, diarrhea, failure to thrive, hepatomegaly with hepatic dysfunction, cataracts with characteristic oil-droplet appearance, renal tubular acidosis
- diagnosed with detection of nonglucose-reducing substance in urine using a Clinitest followed by confirmation of enzyme deficiency in RBCs
- managed with a galactose-free diet (e.g. soy or elemental formulas)
- nearly all females suffer ovarian failure and death in early infancy is possible from E. coli sepsis unless treated early in which case normal intelligence is possible
75
Hereditary Fructose Intolerance
- a fructose-1-phosphate aldolase B deficiency
- onset after the introduction of fruit or fruit juice with severe hypoglycemia, vomiting, diarrhea, failure to thrive, and seizures
- treat with avoidance of fructose, sucrose, and sorbitol
76
Von Gierke's Disease
- an autosomal recessive glycogen storage disease
- caused by glucose-6-phosphatase deficiency
- presents with persistent hypoglycemia, hepatomegaly, metabolic acidosis, hypertriglyceridemia, and large kidneys
- manage with frequency feeding and a high-complex carbohydrate diet
- at increased risk for HCC
77
Pompe's Disease
- an autosomal recessive glycogen storage disease
- caused by an a-glucosidase deficiency
- should be considered in infants with muscular weakness and cardiomegaly
- presents in the first two weeks with flaccid weakness, poor feeding, progressive cardiomegaly, hepatomegaly, and acidosis
78
Medium-Chain Acyl-CoA Dehydrogenase Deficiency
- a fatty acid oxidation defect that typically presents during an acute illness or during fasting
- inability to utilize fatty acids results in non-ketotic hypoglycemia, hyperammonemia, myopathy, and cardiomyopathy
- diagnosed with tandem mass spec detecting elevated plasma medium-chain fatty acids
- manage with frequent feedings with a high-carb, low-fat diet and carnitine supplementation during acute episodes
79
Kearns-Sayre Syndrome
- a mitochondrial disorder
- characterized by ophthalmoplegia, pigmentary degeneration of the retina, hearing loss, heart block, and neurologic decline
- diagnosed based on tissue biopsy
80
MELAS
Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like episodes, which is diagnosed with tissue biopsy
81
Tay-Sachs Disease
- an autosomal recessive lysosomal storage disease more common in Ashkenazi Jews
- caused by hexosaminidase A deficiency
- the infantile-onset form presents with decreasing eye contact, progressive blindness, and a cherry-red macula; hypotonia; hyperacusis causing increased startle; macrocephaly; and severe developmental delay
- the juvenile form begins after 2 years of age with ataxia, dysarthria, and choreoathetosis; cherry-red macula is absent
- the infantile form is untreatable with death in the first four years of life; the juvenile form has a poor prognosis with degeneration into a chronic debilitated state
82
Marfan syndrome can be confused with which inborn error of metabolism? How do they differ?
- it can be confused with homocystinuria
- however, in contrast to Marfan syndrome, there is no arachnodactyly, no upward lens subluxation, and no aortic dilatation in homocystinuria
83
Gaucher's Disease
- an autosomal recessive lysosomal storage disease
- caused by glucocerebrosidase deficiency
- presents with hepatosplenomegaly, thrombocytopenia, and a characteristic Erlenmeyer flask-shape to the distal femur
- management includes enzyme replacement but death should be expected by the age of four
84
Niemann-Pick disease
- a lysosomal storage disease caused by a sphingomyelinase deficiency
- it presents by 6 months of age with neurodegeneration, ataxia, seizures, hepatosplenomegaly, and a cherry-red macula
- death occurs by age four
85
Metachromatic Leukodystrophy
- a lysosomal storage disease and neurodegenerative disorder caused by arylsulfatase A deficiency
- presents with ataxia, seizures, and progressive mental retardation
- death usually occurs by 10-20 years of age
86
What are mucopolysaccharidoses?
a group of lysosomal storage disorders in which glycosaminoglycans accumulate in multiple organs (e.g. Hurler, Hunter, Sanfilippo, and Morquio syndromes)
87
What is dystopia multiplex?
- a syndrome of bony abnormalities seen in those with mucopolysaccharidoses
- includes a thickened cranium; J-shaped sella turcica; malformed, ovoid, or beak-like vertebrae; short and thickened clavicles; and oar-shaped ribs
88
Hurler Syndrome
- an autosomal recessive mucopolysaccharidosis caused by an a-L-iduronidase deficiency
- presents after 1 year of age with developmental delay, hepatosplenomegaly, kyphosis, progressively coarsened facial features, hydrocephalus, progressively stiffening joints, and corneal clouding
- diagnosis is made by finding dermatan and heparan sulfates in the urine
- managed with early bone marrow transplant to prevent neurologic decline but death is usually between 10-15 years of age
89
Hunter Syndrome
- an X-linked recessive mucopolysacchariosis
- presents with hepatosplenomegaly, hearing loss, dystopia multiplex, progressively stiffening joints, and no corneal clouding ("Hunters need sharp eyes")
- diagnosis is made by finding dermatan and heparan sulfates in the urine
90
Sanfilippo Syndrome
- an autosomal recessive mucopolysaccharidosis
| - presents with rapid and severe mental and motor retardation
91
Morquio Syndrome
- an atypical mucopolysaccharidosis because mental retardation is absent
- but severe scoliosis leads to cor pulmonale and death by age 40
92
Acute intermittent Porphyria
- a defect in heme pigment biosynthesis
- episodes are precipitated by drugs, hormonal surges, and poor nutrition
- neurologic findings include personality change, emotional liability, paresthesia, and weakness; there is colicky abdominal pain with vomiting and constipation; autonomic instability; and dark-burgundy-colored urine
- diagnosed based on elevated serum and urine porphobilinogen
- managed with IV glucose, electrolyte correction, and avoidance of fasting as well as precipitating drugs
93
Wilson's Disease
- an autosomal recessive defect in copper excretion
- presents with Kayser-Fleischer rings due to copper deposited in Descemet's membrane, behavior change, dystonia, dysarthria, tremors, ataxia, seizure, and hepatic dysfunction
- low serum ceruloplasmin is a positive screening test; confirmed with elevated serum and urine copper or by liver biopsy
- managed with avoidance of copper-containing foods, penicillamine, and zinc salts to prevent absorption
94
Menkes Disease
- an X-linked recessive defect in copper transport
- presents with myoclonic seizures, pale kinky friable hair, optic nerve atrophy, severe retardation, and progressive neurologic degeneration in the first few months of life
- serum copper is low as is ceruloplasmin
95
How is Wilson's disease differentiated from Menkes?
- both have low serum ceruloplasmin but Menkes also has low serum copper while Wilson's has elevated serum copper
- additionally, Menkes presents in the first few months of life whereas Wilson's presents between age 2-50 depending on how quickly copper accumulates
