The following article covers most of the important points about Hereditary spherocytosis (HS) that are tested in the USMLE exam. Pay close attention to bold phrases as they are key points that appear in the exam as questions/hints.
HS is a common inherited
hemolytic anemia resulting from abnormalities in the proteins of the red
blood cell (RBC) membrane (mainly spectrin but also ankyrin, protein 4.2, and band 3).
It is usually inherited in an autosomal dominant pattern, is most
common in whites of Northern European descent, and is infrequent in
African Americans. (Hereditary elliptocytosis (HE) is another disorder of
the red cell membrane that is a common cause of inherited hemolytic
anemia in African Americans.)
The membrane abnormalities of HS
cause fragility of the red cell membrane with loss of surface area and a
resultant spheroid shape instead of the normal biconcave appearance.
The MCV is usually within the normal range for age, but may be slightly
elevated if there is a brisk reticulocytosis. MCHC is high due to the
relative cellular dehydration.
The abnormal RBCs become trapped in the
spleen where they are eventually hemolyzed (so-called extravascular
hemolysis).
This leads to an increase in LDH, unconjugated bilirubin.
Haptoglobin is a scavenger hor free
hemoglobin and is normal or decreased in HS (as the hemolysis is extravascular).
Osmotic fragility is increased in HS.
Splenectomy is a common treatment but should be delayed until after school going age, if possible, due to the risk of pneumococcal sepsis.
Penicillin prophylaxis is recommended for at least the first 5 years
after splenectomy with some doctors recommending treatment for life.
Showing posts with label Pediatrics. Show all posts
Showing posts with label Pediatrics. Show all posts
Clavice Fracture
Clavicle is the bone most commonly fractured during labor and delivery. Although difficult delivery of the shoulder, or extended arms in breech deliveries increase the chances of a clavicle fractures, they can be present even with a history of a normal delivery.
Diagnosis: In addition to delivery history the following features may point towards the diagnosis:
-Decrease/assymetric movement of the limbs. (This may be evident by presence of an assymetric Moro's reflex)
-Palpable crepitus or bony irregularity early on
-A large callus forms quickly and is generally palpable by age 1 week.
Prognosis is excellent. Treatment, if any, is limited to immobilization of the arm and shoulder on the affected side (simply pinning the sleeve to the side of the infant's shirt does the trick). Figure of 8 bandages are no longer used.
Differential diagnosis: Congenital pseudoarthrosis of the clavicle
This condition presents as a palpable lump in the center of the clavicle that does not change or heal with any amount of time. Its cause is unknown. The condition is more common on the right side and generally does not lead to any functional impairment. Surgery is rarely indicated.
Diagnosis: In addition to delivery history the following features may point towards the diagnosis:
-Decrease/assymetric movement of the limbs. (This may be evident by presence of an assymetric Moro's reflex)
-Palpable crepitus or bony irregularity early on
-A large callus forms quickly and is generally palpable by age 1 week.
Prognosis is excellent. Treatment, if any, is limited to immobilization of the arm and shoulder on the affected side (simply pinning the sleeve to the side of the infant's shirt does the trick). Figure of 8 bandages are no longer used.
Differential diagnosis: Congenital pseudoarthrosis of the clavicle
This condition presents as a palpable lump in the center of the clavicle that does not change or heal with any amount of time. Its cause is unknown. The condition is more common on the right side and generally does not lead to any functional impairment. Surgery is rarely indicated.
Asperger syndrome vs Autism key points
Asperger disorder
-Impairment in social interaction (few interests)
-They are aware that they do not fit in socially.
-Unlike autistic children, they do not express basic language impairment (only minor problems)
-Treatment is behavior modification and cognitive-behavioral therapy are used to improve level of function.
-Some consider this condition as high functioning autism
Autism
-Usually manifests itself before age 3 years (Asperger may be later)
-Triad of
---Impairment in social interaction (no friends, no empathy)
---Language delay
---Ritualistic behaviors and a strong need for sameness and consistency
-Treatment includes intense family support, behavior modification, speech and language training, auditory integration training, and medication.
-Impairment in social interaction (few interests)
-They are aware that they do not fit in socially.
-Unlike autistic children, they do not express basic language impairment (only minor problems)
-Treatment is behavior modification and cognitive-behavioral therapy are used to improve level of function.
-Some consider this condition as high functioning autism
Autism
-Usually manifests itself before age 3 years (Asperger may be later)
-Triad of
---Impairment in social interaction (no friends, no empathy)
---Language delay
---Ritualistic behaviors and a strong need for sameness and consistency
-Treatment includes intense family support, behavior modification, speech and language training, auditory integration training, and medication.
Epstein's pearls and Bohn's nodules
Epstein's pearls are tiny cystic lesions of the palate found in approximately 2/3rds of newborns. They are visible over the region of fusion of the posterior palatal segments and are a result of the inclusion of epithelial cells during palatal fusion. Bohn's nodules are also benign and much less frequent than Epstein's pearls. They occur along the junction of the hard and soft palate or adjacent to the midpalatal raphe and are derived from epithelial remnants of developing palatal salivary glands. Distinction between Epstein's pearls and Bohn's nodule is difficult and clinically irrelevant because both of these lesions regress and require no treatment.
Do not confuse these with the following conditions:
Congenital epulis is a very rare tumor seen in the newborn period (especially in females). It is usually firm and pedunculated and visible on the anterior alveolar ridge of the maxilla. It is benign in nature but may lead to difficulty with feeding and/or respiration requiring excision.
Mucoceles are clear fluid-filled, well-circumscribed, small lesions usually visible on the labial mucosa of the lower lip. These occur as a result of trauma to a submucosal salivary duct, usually from blunt trauma or lip biting. They usually also require no treatment. Large lesions may be de-roofed.
Do not confuse these with the following conditions:
Congenital epulis is a very rare tumor seen in the newborn period (especially in females). It is usually firm and pedunculated and visible on the anterior alveolar ridge of the maxilla. It is benign in nature but may lead to difficulty with feeding and/or respiration requiring excision.
Mucoceles are clear fluid-filled, well-circumscribed, small lesions usually visible on the labial mucosa of the lower lip. These occur as a result of trauma to a submucosal salivary duct, usually from blunt trauma or lip biting. They usually also require no treatment. Large lesions may be de-roofed.
Rett syndrome key points
Rett syndrome
-X-linked dominant (Affects girls).
-Onset is in the second year of life.
-Typically there is regression in motor and language development
-Autistic behaviors are common
-There is acquired microcephaly
-Characteristic hand-wringing behavior
Poor prognosis. No specific treatment.
-X-linked dominant (Affects girls).
-Onset is in the second year of life.
-Typically there is regression in motor and language development
-Autistic behaviors are common
-There is acquired microcephaly
-Characteristic hand-wringing behavior
Poor prognosis. No specific treatment.
Angelman Syndrome vs. Prader Willi Syndrome: Genetics and Clinical Features
Prader-Willi and Angelman syndromes are the two most common genetic disorders of imprinting. The concept of imprinting lies in the fact that the function of certain genes is dependent on their parents: maternal or paternal. Basically there is something wrong with the 15q11 region of the paternally derived chromosome in Prader Willi syndrome and that of the maternally derived chromosome in Angelman syndrome.
Prader-Willi phenotype can occur as a result of one of the following
1. Deletion of 15q11-q13 including the Prader-Willi critical region of the paternally derived chromosome 15 (most common)
2. Abnormality of the structure of Prader-Willi critical region of 15q11-q13 (for example translocation)
3. If the child has two maternally derived chromosome 15s. (Hence absence of paternal chromosome 15)
4. Mutations of imprinting control center genes (rare)
The critical region of chromosome 15 for Angelman syndrome is located very close to the Prader-Willi critical region. But, when deletion of the Angelman critical region results, it is the maternally derived chromosome that is affected.
Mechanisms leading to Angelman syndrome include the following:
1. Deletion of the 15q11-q13 including the Angelman critical region of the maternally derived chromosome 15 (most common)
2. Abnormality of the structure of the Angelman critical region of 15q11-q13 (e.g. translocation)
3. If the child has two paternally derived chromosome 15s. (Hence absence of maternal chromosome 15)
4. Mutations of imprinting control center genes (rare).
5. Mutations of the ubiquitin-protein ligase gene (UBE3A)
6. No identifiable etiologic mechanisms but a positive family history of other affected individuals and a classic phenotype
Clinical features of Prader Willi syndrome:
Newborns: hypotonia, poor sucking and swallowing, weak cry
Infancy: Delayed motor and speech development
Toddler: Hypotonia goes away! Extreme appetite leading to morbid obesity.
In addition hands and feet are noticeably small from birth, height is short and the penis and testes are hypoplastic. Patients have emotional lability and extreme temper tantrums.
Clinical features of Angelman syndrome:
Severe cognitive deficits; speech is heavily impared. Inappropriate paroxysms of laughter (happy puppets). Physical features include microcephaly, maxillary hypoplasia, large mouth, and short stature.Seizures are common. Except for case reports, all patients are infertile.
Prader-Willi phenotype can occur as a result of one of the following
1. Deletion of 15q11-q13 including the Prader-Willi critical region of the paternally derived chromosome 15 (most common)
2. Abnormality of the structure of Prader-Willi critical region of 15q11-q13 (for example translocation)
3. If the child has two maternally derived chromosome 15s. (Hence absence of paternal chromosome 15)
4. Mutations of imprinting control center genes (rare)
The critical region of chromosome 15 for Angelman syndrome is located very close to the Prader-Willi critical region. But, when deletion of the Angelman critical region results, it is the maternally derived chromosome that is affected.
Mechanisms leading to Angelman syndrome include the following:
1. Deletion of the 15q11-q13 including the Angelman critical region of the maternally derived chromosome 15 (most common)
2. Abnormality of the structure of the Angelman critical region of 15q11-q13 (e.g. translocation)
3. If the child has two paternally derived chromosome 15s. (Hence absence of maternal chromosome 15)
5. Mutations of the ubiquitin-protein ligase gene (UBE3A)
6. No identifiable etiologic mechanisms but a positive family history of other affected individuals and a classic phenotype
Clinical features of Prader Willi syndrome:
Newborns: hypotonia, poor sucking and swallowing, weak cry
Infancy: Delayed motor and speech development
Toddler: Hypotonia goes away! Extreme appetite leading to morbid obesity.
In addition hands and feet are noticeably small from birth, height is short and the penis and testes are hypoplastic. Patients have emotional lability and extreme temper tantrums.
Clinical features of Angelman syndrome:
Severe cognitive deficits; speech is heavily impared. Inappropriate paroxysms of laughter (happy puppets). Physical features include microcephaly, maxillary hypoplasia, large mouth, and short stature.Seizures are common. Except for case reports, all patients are infertile.
Caput succedaneum vs. Cephalhematoma
Caput succedaneum is a common and benign condition in which head compression against the cervix impedes venous return. It has the following characteristics
- Apparent usually at birth
- Crosses suture lines
- Reabsorbs within 1-3 days
Cephalhematoma (also spelled as cephalohematoma cephalhaematoma and cephalohaematoma) on the other hand is collection of blood below the periosteum. It has the following characteristics.
- Typically becomes apparent 1-2 days after birth
- It does not cross the suture lines (because it is under the periosteum).
- Takes 3-4 weeks or longer for it to be reabsorbed
- Can lead to jaundice from degradation of the extravasated blood
- Often associtated with birth trauma and a fracture in the newborn's skull bones (most commonly parietal bone)
- Apparent usually at birth
- Crosses suture lines
- Reabsorbs within 1-3 days
Cephalhematoma (also spelled as cephalohematoma cephalhaematoma and cephalohaematoma) on the other hand is collection of blood below the periosteum. It has the following characteristics.
- Typically becomes apparent 1-2 days after birth
- It does not cross the suture lines (because it is under the periosteum).
- Takes 3-4 weeks or longer for it to be reabsorbed
- Can lead to jaundice from degradation of the extravasated blood
- Often associtated with birth trauma and a fracture in the newborn's skull bones (most commonly parietal bone)
Lead screening, levels and treatment in children
Current guidelines state that health-care professionals should use blood lead tests to screen children at ages 1 and 2 years. Older children should be screened in certain high risk situations.
The American Academy of Pediatrics policy statement recommends the use of venous samples for initial screening whenever possible. If capillary testing is performed and the lead concentration is greater than 10 mcg/dL, the lead concentration must be confirmed by a venous sample because capillary sampling is more likely to yield false-positive results due to contamination from skin.
Chelation therapy should be considered if lead concentrations are higher than 44 mcg/dL. The role of chelation is not clearly defined for children whose blood lead concentrations range from 20 to 45 mcg/dL. Levels below 20 mcg/dL can be monitored periodically.
Succimer is the drug of choice for children whose blood lead concentrations are > 45 mcg/dL. For levels >70 mcg/dL calcium-disodium EDTA can be added. The first dose always is succimer, followed 4 hours later by EDTA, because EDTA when given alone can worsen lead encephalopathy.
Hemorrhagic Disease of the Newborn
Three forms of hemorrhagic disease of the newborn are recognized. The phrase is a misnomer because these can be seen during infancy after the neonatal period.
1) Early-onset: Typically presents during first 24 hours after birth and is seen in infants born to mothers who are deficient in vitamin K (those who are on seizure or tuberculosis medications). Site of bleeding is variable and can be serious (intracranial).
2) Classic: Presents between day 1 to 7 of life and is secondary to failure of administration of vitamin K at birth. Site of bleeding can be umbilicus, GI, skin, circumcision. Intracranial bleeding is less common.
3) Late: Presents from 2 weeks up to 6 months (rarely later) and is seen in exclusively or predominantly breastfed infants who did not get vitamin K at birth. Most common presentation is intracranial hemorrhage.
Treatment: Symptomatic (transfusion, supportive care, site specific treatment), FFP for active bleeding, vitamin K administration.
1) Early-onset: Typically presents during first 24 hours after birth and is seen in infants born to mothers who are deficient in vitamin K (those who are on seizure or tuberculosis medications). Site of bleeding is variable and can be serious (intracranial).
2) Classic: Presents between day 1 to 7 of life and is secondary to failure of administration of vitamin K at birth. Site of bleeding can be umbilicus, GI, skin, circumcision. Intracranial bleeding is less common.
3) Late: Presents from 2 weeks up to 6 months (rarely later) and is seen in exclusively or predominantly breastfed infants who did not get vitamin K at birth. Most common presentation is intracranial hemorrhage.
Treatment: Symptomatic (transfusion, supportive care, site specific treatment), FFP for active bleeding, vitamin K administration.
Clinical Presentation, Diagnosis and Treatment of Celiac Disease
Celiac disease immune mediated disease in which the body makes antibodies against tissue transglutaminase (tTG) enzyme. Gluten is the most important environmental trigger and the disease has specific association with class II haplotypes of HLA DQ2 (haplotypes DR17 or DR5 or 7) and, DQ8 (haplotype DR4).
Clinical presentation: Typically it presents with abdominal symptoms between 6 months to 2 years of age (Age at which gluten is introduced in the diet). Symptoms include diarrhea, poor appetite, abdominal pain, emesis and failure to thrive. Celiac crisis can be a rare presentation in which the patient has severe watery diarrhea, bloating, dehydration, electrolyte imbalance(low K) and shock. Older children can present with nausea, vomiting, recurrent stomachache, constipation, diarrhea, anemia and stunting of growth.
Diagnosis: Antigliadin (AGA) tests were commonly used but now have fallen out of favor due to low sensitivity and specificity. The IgA endomysium (EMA-IgA) and tissue transglutaminase (TTG-IgA) tests are currently the tests of choice due to their high specificity. Diagnosis has to be confirmed by duodenal biopsy A minimum of 4 biopsy samples are recommended as patchy involvement is common.
Treatment: Complete avoidance of gluten is the key. This means avoiding Wheat, rye, barley. Oats are considered safe.
Treatment of Acute Otitis Media (AOM) in Children
Acute otitis media is the commonest diagnosis in sick children visiting the pediatrician's office in the United States.
Middle ear effusion is common after the resolution of acute symptoms. It may persist for three months in 10%. If persistent it can cause conductive hearing loss and may affect speech, language, and cognitive ability.
Treatment of involves pain relief and antibiotics.
Motrin (ibuprofen), Tylenol(crocin/parecetamol/acetaminophen) are effective for pain.
Less than 24 month olds should always get antibiotics. Older kids with bilateral infection should also always get antibiotics. Otherwise healthy, older children with unilateral infection may be observed without antibiotics.
Amoxicillin is the usual first-line therapy and duration is usually 7 days. If they persist to have symptoms despite 48-72 hours of treatment may be changed to Augmentin(amoxicillin-clavulinic acid).
Less than 2 year olds and older kids with language deficits should have a follow up visit 2-3 months from the acute infection to ensure resolution of effusion.
Middle ear effusion is common after the resolution of acute symptoms. It may persist for three months in 10%. If persistent it can cause conductive hearing loss and may affect speech, language, and cognitive ability.
Treatment of involves pain relief and antibiotics.
Motrin (ibuprofen), Tylenol(crocin/parecetamol/acetaminophen) are effective for pain.
Less than 24 month olds should always get antibiotics. Older kids with bilateral infection should also always get antibiotics. Otherwise healthy, older children with unilateral infection may be observed without antibiotics.
Amoxicillin is the usual first-line therapy and duration is usually 7 days. If they persist to have symptoms despite 48-72 hours of treatment may be changed to Augmentin(amoxicillin-clavulinic acid).
Less than 2 year olds and older kids with language deficits should have a follow up visit 2-3 months from the acute infection to ensure resolution of effusion.
Propionic acidemia
Propionic acidemia is an autosomal recessive disorder in which the body is unable to process certain parts of proteins and lipids. It is classified as an organic acid disorder (organic acids build up).
Diagnosis:
Symptoms appear within a few days of birth and include vomiting, poor feeding, hypotonia and lethargy. Leukocyte propionyl CoA carboxylase activity is the study required for definitive biochemical diagnosis and appropriate genetic counseling. Blood ammonia levels (elevated secondarily), Lactate levels, electrolytes, Urine ketones are other tests recommended in this condition. Anion gap will be increased due to increased unmeasured acids. ECG is recommended in all patients because of increased risk of prolonged QTc interval.
Pathophysiology:
The enzyme propionyl-CoA carboxylase is dysfunctional in propionic acidemia. Mutations in the PCCA and PCCB genes are responsible. As a result propionyl CoA accumulates in the body.
Treatment:
In acute illness - extra calories. No proteins. Once clinical condition improves can resume proteins at a very low concentration using special formulas that lack in isoleucine, valine, threonine, methionine
Diagnosis:
Symptoms appear within a few days of birth and include vomiting, poor feeding, hypotonia and lethargy. Leukocyte propionyl CoA carboxylase activity is the study required for definitive biochemical diagnosis and appropriate genetic counseling. Blood ammonia levels (elevated secondarily), Lactate levels, electrolytes, Urine ketones are other tests recommended in this condition. Anion gap will be increased due to increased unmeasured acids. ECG is recommended in all patients because of increased risk of prolonged QTc interval.
Pathophysiology:
The enzyme propionyl-CoA carboxylase is dysfunctional in propionic acidemia. Mutations in the PCCA and PCCB genes are responsible. As a result propionyl CoA accumulates in the body.
Treatment:
In acute illness - extra calories. No proteins. Once clinical condition improves can resume proteins at a very low concentration using special formulas that lack in isoleucine, valine, threonine, methionine
Febrile seizures
A febrile seizure is defined by the following:
-3 months and 5 years of age
-associated with fever but without evidence of intracranial infection.
-Seizures with fever in children with history of nonfebrile seizures are excluded.
Typical febrile seizures:
-Lasts <15 minutes
-Occurs no more than once in 24 hours
-Is generalized tonic clonic
Lumbar puncture is Indicated only to rule out meningitis or encephalitis if signs or symptoms suggestive of these illnesses are present.
Treatment of simple/typical febrile seizures:
Treat the cause of fever (most are viral infections and do not require antibiotics). Antipyretics are used in adequate amounts until the risk of fever abates. Antipyretics are of no direct value in preventing febrile seizures or their recurrence nor do they slow temperature elevation during fever.
-3 months and 5 years of age
-associated with fever but without evidence of intracranial infection.
-Seizures with fever in children with history of nonfebrile seizures are excluded.
Typical febrile seizures:
-Lasts <15 minutes
-Occurs no more than once in 24 hours
-Is generalized tonic clonic
Lumbar puncture is Indicated only to rule out meningitis or encephalitis if signs or symptoms suggestive of these illnesses are present.
Treatment of simple/typical febrile seizures:
Treat the cause of fever (most are viral infections and do not require antibiotics). Antipyretics are used in adequate amounts until the risk of fever abates. Antipyretics are of no direct value in preventing febrile seizures or their recurrence nor do they slow temperature elevation during fever.
When to chelate for lead toxicity?
Indication:
Chelation therapy should be considered for lead toxicity if lead concentrations are higher than 44.0 mcg/dL. For levels between 10 and 44 frequent monitoring is recommended.
Drugs:
Succimer is the drug of choice for children whose blood lead concentrations are 45.0 to 100.0 mcg/dL . At values higher than 69.0 mcg/dL, a second drug, Calcium Disodium EDTA (Not to be confused with Sodium EDTA), is added. The first dose always is succimer, followed 4 hours later by EDTA, because children who present with lead encephalopathy may deteriorate when treated with EDTA alone.
Blood lead levels fall rapidly after chelation, but rebound within weeks, even if there is no further exposure to lead, due to release of lead from bone stores. These levels usually are not high enough to indicate chelation but if they do a second round of chelation may be needed.
Chelation therapy should be considered for lead toxicity if lead concentrations are higher than 44.0 mcg/dL. For levels between 10 and 44 frequent monitoring is recommended.
Drugs:
Succimer is the drug of choice for children whose blood lead concentrations are 45.0 to 100.0 mcg/dL . At values higher than 69.0 mcg/dL, a second drug, Calcium Disodium EDTA (Not to be confused with Sodium EDTA), is added. The first dose always is succimer, followed 4 hours later by EDTA, because children who present with lead encephalopathy may deteriorate when treated with EDTA alone.
Blood lead levels fall rapidly after chelation, but rebound within weeks, even if there is no further exposure to lead, due to release of lead from bone stores. These levels usually are not high enough to indicate chelation but if they do a second round of chelation may be needed.
Kawasaki Disease
Diagnostic Criteria for Kawasaki
Presence of fever for at least 5 days and at least four of five criteria:
- Bilateral conjunctival injection without exudate
- Polymorphous rash
- Changes in lips and mouth (Reddened, dry, or cracked lips, Strawberry tongue, Diffuse redness of oral cavity or pharynx)
- Changes in extremities (Reddening of palms or soles, Indurative edema of hands or feet, Desquamation of skin of hands, feet, and groin (in convalescence)
- Cervical lymphadenopathy (More than 15 mm in diameter, usually unilateral, single, non-purulent, and painful)
- Bilateral conjunctival injection without exudate
- Polymorphous rash
- Changes in lips and mouth (Reddened, dry, or cracked lips, Strawberry tongue, Diffuse redness of oral cavity or pharynx)
- Changes in extremities (Reddening of palms or soles, Indurative edema of hands or feet, Desquamation of skin of hands, feet, and groin (in convalescence)
- Cervical lymphadenopathy (More than 15 mm in diameter, usually unilateral, single, non-purulent, and painful)
Exclusion of other conditions with similar clinical picture like:
Staphylococcal scalded skin syndrome, toxic shock syndrome
Scarlet fever
Stevens-Johnson syndrome
Drug reaction
Juvenile rheumatoid arthritis
Alkaptonuria
Alkaptonuria is caused by inherited deficiency of the liver enzyme homogentisic aicd dioxygenase. This leads to accumulation of homogentisic acid, which is rapidly cleared in the kidney and excreted.
When homogentisic acid comes on contact with air, it is oxidized to form a black colored compound. Hence the urine of these patient turns black on standing. Kidneys are efficient at clearing homogentisic acid initially but eventually it gets deposited in various tissues.
The earliest symptom may be the mother noticing a black diapers. Ochronosis, which is visible deposition of the pigment in tissues usually does not occur before the fourth decade. The tissues most commonly involved include cartilage, sclera. This leads to joint problems. It is speculated that heart disease including myocardial infarction may be more common but there is not enough statistical evidence.
When homogentisic acid comes on contact with air, it is oxidized to form a black colored compound. Hence the urine of these patient turns black on standing. Kidneys are efficient at clearing homogentisic acid initially but eventually it gets deposited in various tissues.
The earliest symptom may be the mother noticing a black diapers. Ochronosis, which is visible deposition of the pigment in tissues usually does not occur before the fourth decade. The tissues most commonly involved include cartilage, sclera. This leads to joint problems. It is speculated that heart disease including myocardial infarction may be more common but there is not enough statistical evidence.
Smith-Lemli-Opitz syndrome/RSH syndrome
Initially described in 1964 this is an inborn error of metabolism of in the steroid synthesis pathway. This syndrome was initially called RSH after the first initial of the last names of the first 3 patients evaluated!
This syndrome is caused by a deficiency of the microsomal enzyme DHCR7(Dehydrocholesterol reductase 7), which is responsible for conversion of 7DHC to cholesterol as the last step in cholesterol synthesis. Affected children hence have low plasma cholesterol levels and elevated levels of cholesterol precursors (e.g. 7DHC).
Clinical features are variable and include llethargy, rrespiratory failure, deafness, feeding difficulties, failure to thrive, photosensitivity, mental retardation, autism, antisocial, self-destructive, and violent acts , intrauterine growth retardation (IUGR), microcephaly, broad nasal tip with anteverted nostrils, micrognathia, ptosis, squint, congenital cataracts, low-set ears, syndactyly and/or polydactyly, hypospadias or cryptorchidism in males and ambiguous genitalia in females, cleft palate and congenital cardiac defects.
Juvenile rheumatoid arthritis (JRA) - Classification and epidemiology
JRA (Now also called Juvenile idiopathic arthritis or JIA) is one of the most common chronic joint disorders in kids. It is classified as follows.
1) Pauciarticular disease: (About 50% of all JRA cases) Less than 5 joints are involved. Usually large joints, such as the shoulder, elbow, hip, and knee are affected. Pauciarticular JRA is most common in kids younger than 8 years. There is 20-30% chance of developing iridocyclitis.
2) Polyarticular disease: (30% of all JRA cases) As the name suggests this type affects more than 5 joints. Unlike the pauciarticular type small joints such as those in the hands and feet are often involved.
3) Systemic onset JRA (a.k.a Stills disease, 20% of all JRA). Children present with high fevers, skin rashes, and joint pain. Acute leukemia must be excluded as it can present identically.
1) Pauciarticular disease: (About 50% of all JRA cases) Less than 5 joints are involved. Usually large joints, such as the shoulder, elbow, hip, and knee are affected. Pauciarticular JRA is most common in kids younger than 8 years. There is 20-30% chance of developing iridocyclitis.
2) Polyarticular disease: (30% of all JRA cases) As the name suggests this type affects more than 5 joints. Unlike the pauciarticular type small joints such as those in the hands and feet are often involved.
3) Systemic onset JRA (a.k.a Stills disease, 20% of all JRA). Children present with high fevers, skin rashes, and joint pain. Acute leukemia must be excluded as it can present identically.
EEG findings in Absense seizures/ Petit mal epilepsy
Electroencephalographic findings in typical absence seizures (petit mal epilepsy) are as follows:
1) Background activity is normal.
2) Frontally dominant bursts of 3-Hz spike-and-wave complexes are seen during the seizures.
3) In syndromes with less frequent absence seizures (juvenile absence epilepsy or juvenile myoclonic epilepsy), an awake recording may be normal; a sleep or sleep-deprived recording may show evidence of generalized 3-Hz spike-and-wave complexes.
4) There is abrupt onset and ending. No postictal EEG slowing is noted.
5) Video EEG may demonstrate that clinical seizures at times occur after the the start of ictal EEG activity by a few seconds.
1) Background activity is normal.
2) Frontally dominant bursts of 3-Hz spike-and-wave complexes are seen during the seizures.
3) In syndromes with less frequent absence seizures (juvenile absence epilepsy or juvenile myoclonic epilepsy), an awake recording may be normal; a sleep or sleep-deprived recording may show evidence of generalized 3-Hz spike-and-wave complexes.
4) There is abrupt onset and ending. No postictal EEG slowing is noted.
5) Video EEG may demonstrate that clinical seizures at times occur after the the start of ictal EEG activity by a few seconds.
prGCD - plant cell expressed recombinant Glucocerebrosidase enzyme (GCD) for use in Gaucher's disease
This is a newly approved (partially approved for use by the Food and Drug Administration-FDA) drug for the treatment of patients with Gaucher's Disease.
Gaucher's disease is the most common lysosomal storage diseases in humans. It is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as acid β-glucosidase). The enzyme acts on glucocerebroside which accumulates in its absence. Fatty material collects in the liver, kidneys, lungs, spleen, brain and bone marrow. The disease is inherited in autosomal recessive manner. The locus is on chromosome 1.
Traditionally Gaucher's disease has been classified in the following 3 types.
Type I (or non-neuropathic type) is the most common form of the disease. It occurs in 1 in 50,000 births. It is much more frequent in children of Ashkenazi Jewish heritage. Symptoms include enlarged liver and spleen. Bone marrow replacement can cause anemia, thrombocytopenia and leukopenia. The brain is usually not affected. Rarely there is lung or kidney impairment. These patients may live well into adulthood.
Type II (or acute infantile neuropathic form) typically begins in infancy and occurs in approximately 1 in 100,000 births. The diagnostic symptom of this type is extensive and progressive brain damage. Affected children do not usually live longer than 2 years of age.
Type III (the chronic neuropathic type) has a variable onset. Incidence is 1 in 100,000 births. It is characterized by slowly progressive but milder neurologic symptoms. Other major symptoms include an spleen and/or liver enlargement, seizures, bone marrow disorders and respiratory problems.
Gaucher's disease is the most common lysosomal storage diseases in humans. It is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as acid β-glucosidase). The enzyme acts on glucocerebroside which accumulates in its absence. Fatty material collects in the liver, kidneys, lungs, spleen, brain and bone marrow. The disease is inherited in autosomal recessive manner. The locus is on chromosome 1.
Traditionally Gaucher's disease has been classified in the following 3 types.
Type I (or non-neuropathic type) is the most common form of the disease. It occurs in 1 in 50,000 births. It is much more frequent in children of Ashkenazi Jewish heritage. Symptoms include enlarged liver and spleen. Bone marrow replacement can cause anemia, thrombocytopenia and leukopenia. The brain is usually not affected. Rarely there is lung or kidney impairment. These patients may live well into adulthood.
Type II (or acute infantile neuropathic form) typically begins in infancy and occurs in approximately 1 in 100,000 births. The diagnostic symptom of this type is extensive and progressive brain damage. Affected children do not usually live longer than 2 years of age.
Type III (the chronic neuropathic type) has a variable onset. Incidence is 1 in 100,000 births. It is characterized by slowly progressive but milder neurologic symptoms. Other major symptoms include an spleen and/or liver enlargement, seizures, bone marrow disorders and respiratory problems.
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