This case presentation describes a 29-day old male child presenting with increased crying, lip smacking, frequent urination, and increased skin pigmentation. Examination found the child to be severely dehydrated and biochemical tests showed hyponatremia and hyperkalemia. Differential diagnoses included congenital adrenal hyperplasia. Testing found highly elevated 17-hydroxyprogesterone, confirming congenital adrenal hyperplasia. The child was diagnosed with the salt-wasting form of 21-hydroxylase deficiency congenital adrenal hyperplasia.
This is a powerpoint file of an MBBS practical class taken by Dr. Karthikeyan Pethusamy at All India Institute of Medical Sciences - NewDelhi.
Disclaimer: The views expressed here are of the author only not of the institution.
This is a powerpoint file of an MBBS practical class taken by Dr. Karthikeyan Pethusamy at All India Institute of Medical Sciences - NewDelhi.
Disclaimer: The views expressed here are of the author only not of the institution.
Inborn errors of metabolism
Definition:- Inborn errors of metabolism occur from a group of rare genetic disorders in which the body cannot metabolize food components normally.
These disorders are usually caused by defects in the enzymes involved in the biochemical pathways that break down food components.
inborn errors of metabolism. Inborn errors of metabolism are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food
An inherited enzyme deficiency leading to the disruption of normal bodily metabolism.
Accumulation of a toxic substrate.
Impaired formation of a product normally produced by the deficient enzyme.
A presentation on aminoaciduria as inborn errors of metabolism, with emphasis on the screening test ...had some animations which enhanced the presentation...but slideshare does not allow animations... so maybe dull and boring for some...
IEM comprise a group of disorders in which a single gene defect causes a clinically significant block in a metabolic pathway resulting either in accumulation of substrate behind the block or deficiency of the product.
Clinical Reasoning: How Some Doctors Think and the Rest of Us Try ToSHMLive
Case presentations for Dr. Dan Brotman's session at Hospital Medicine 2015. An expert clinician is brought in to try to troubleshoot medical cases on the spot, and attendees try to come to the best conclusion before the expert. "Clinical Reasoning: How Some Doctors Think and the Rest of Us Try To" is a session at the Society of Hospital Medicine's annual meeting, Hospital Medicine 2015 held March 30th to April 1st.
Inborn errors of metabolism
Definition:- Inborn errors of metabolism occur from a group of rare genetic disorders in which the body cannot metabolize food components normally.
These disorders are usually caused by defects in the enzymes involved in the biochemical pathways that break down food components.
inborn errors of metabolism. Inborn errors of metabolism are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food
An inherited enzyme deficiency leading to the disruption of normal bodily metabolism.
Accumulation of a toxic substrate.
Impaired formation of a product normally produced by the deficient enzyme.
A presentation on aminoaciduria as inborn errors of metabolism, with emphasis on the screening test ...had some animations which enhanced the presentation...but slideshare does not allow animations... so maybe dull and boring for some...
IEM comprise a group of disorders in which a single gene defect causes a clinically significant block in a metabolic pathway resulting either in accumulation of substrate behind the block or deficiency of the product.
Clinical Reasoning: How Some Doctors Think and the Rest of Us Try ToSHMLive
Case presentations for Dr. Dan Brotman's session at Hospital Medicine 2015. An expert clinician is brought in to try to troubleshoot medical cases on the spot, and attendees try to come to the best conclusion before the expert. "Clinical Reasoning: How Some Doctors Think and the Rest of Us Try To" is a session at the Society of Hospital Medicine's annual meeting, Hospital Medicine 2015 held March 30th to April 1st.
Clinical orthodontic presentation - orthodontic presentation - Case presenta...King Saud Medical City
Clinical orthodontic presentation - orthodontic presentation - Case presentation of ortho - ortho presentation - clinical case presentation
case ortho - orthodontic case presentation
Congenital Adr Hyperplasia (CAH) can appear at any age from birth to puberty where it can lead to ambiguous genitalia. It is due to absolute or relative deficiency of 17 Hydroxylase or 21 Hydroxylase enzyme.
Case Review of Adult-onset Congenital Adrenal Hyperplasia due to 21-OH defici...Shinjan Patra
I have presented a case of adult-onset 21-OH deficiency CAH who presented withj Primary Amenorrhea. Additionally i have also covered the aspects of Diagnosis, neoboen screening, treatment and monitoring of 21-OH deficiency CAH
THIS PRESENTATION IS FOCUSSES ON CONGENITAL HYPERPLASIA, ITS DEFINITION, EPIDEMIOLOGY, ITS TYPES, PATHOGENESIS DIAGNOSIS AND MANAGEMENT OPTIONS IT DESCRIBES HOW CAH AFFECTS ON BODY, AND HOW BODY RESPONSES TO THIS CONDITION THIS IS THE CONDITION IN WHICH ADRENOMEGALY IS SEEN
Congenital Adrenal Hyperplasia (CAH)
For 5th Year Medical Students and Endocrinology Modules and Master and MD Degree Internal Medicine and Endocrinology
By Dr Usama Ragab Youssif
References: Oxford Handbook of Endocrinology & Diabetes
2. Case History
• 29 days male child
• Product of a nonconsanguineous marriage
• Brought to a tertiary centre with complaints
of:
Increased crying spells
Lip smacking
Passage of urine more than 40 times a day
Increase tan of the skin
3. Case history..
• The mother, gave history that the baby was
always hungry and thirsty.
• On 18th day of birth the child developed
severe vomiting treated with antiemetics.
• The baby became lethargic and severely
dehydrated hence referred
6. Differential Diagnosis
• Congenital Hypertrophic Pyloric Stenosis
• Metabolic Syndromes: Congenital adrenal
hyperplasia
USG Abdomen normal study
Gastroenterologist Consultation ruled out
Hypertropic Pyloric Stenosis
7. Diagnosis
• Based on these facts high index of suspicion of
salt losing type of congenital Adrenal
Hyperplasia was made.
• 17 OH progesterone was 240ng/mL [ 0.10-9.4
ng/mL for age group 3 days- 2 months]
• This test confirmed the diagnosis of
Congenital Adrenal Hyperplasia
10. Adrenal Glands
• The adrenal glands; located in the
retroperitoneum superior to the kidneys.
• Triangular in shape and situated bilaterally.
• The weight in an adult human ranges from 4-
6 gram each
14. Biosynthesis of Adrenocortical
Hormones
• Cholesterol ester-----esterase-->free cholesterol +
FFA
• sTAR ( steroidogenic acute regulatory protein)-
--> transports cholesterol to mitochondria
(rate limiting step).
• In the mitochondria cholesterol is converted
to Pregnenolone by 20 α hydroxylase
16. Adreno-cortical Hormones in
Circulation
• Steroid hormones are 90-95% bound to
specific carrier protein or albumin.
• Steroid sulfated / glucuronidated circulate
unbound in plasma
• 80-90% of cortisol is carried by Corticosteroid
Binding Globulin( CBG)
17. Metabolism of Adrenal Steroids
• Major site of steroid metabolism is P450 system
in the liver.
• Clearance of steroid hormones involve:
Hydroxylation
Dehydrogenation
Reduction of double bonds
Conjugation to sulfates and glucuronides
18. Urinary metabolites
• Urinary excretion of these metabolites are
helpful in the estimation of adrenal disease
Hydroxylation
• 17 OH progesterone- pregnanetriol.
• 24- hr urine estimation was done for
estimation of pregnantriol before the advent
of immunoassay for diagnosis of CAH
19. Urinary metabolites…
• Urinary metabolites of 11-deoxycortisol and
cortisol (17 hydroxycorticosteroids )have been
used to differentiate between 21 or 11
hydroxylase deficiency.
• Both are decreased in 21 α hydroxylase
deficiency, whereas deoxycortisol increased in
11 β- hydroxylase deficiency
20. Introduction
• Congenital Adrenal Hyperplasia ( CAH) is the
most common cause of adrenocortical
insufficiency in newborns.
• It presents with a mixed picture of cortisol
deficiency and adrenal androgen
overproduction.
21. Cause
• CAH results from loss of function mutations in
specific adrenocortical enzymes responsible
for the synthesis of cortisol.
• Inherited as autosomal recessive trait
• 21-Hydroxylase deficiency which is one of the
most common defects of adrenal
steroidogenesis.
22. Cause..
• Insufficient cortisol production increase in
ACTH concentration- stimulate the adrenal
hyperplasia in utero .
• Incidence of 21 alpha hydroxylase CAH in
western societies varies from 1 in 5000 to
15,000 live births
23. Cause..
• 95% of CAH result from 21 alpha hydroxylase
and remaining 11 beta hydroxylase deficiency.
• Screening for these enzyme deficient
newborn measure 17-alpha-
hydroxyprogesterone (17-OHP)
24. Cause..
• The metabolic block in cortisol biosynthesis
leads to an accumulation of precursors of
adrenal androgens.
• Measurement of precursor steroid is helpful in
identifying the specific enzyme defect.
25. Cause..
• A partial block in enzyme activity may cause
marked or subtle clinical manifestation,
whereas complete enzyme block is
incompatible with life
• The closer the block to the final cortisol
production, less life threatening are the
symptoms
26. Cause..
• There are two 21-hydroxylase genes in man, A and
B.
• Only the 21-hydroxylase B gene is thought to be
active
27. Cortisol Deficiency
• Malaise
• Failure to thrive
• Hypoglycemia
• Vascular instability
• Approx 75% of classic 21-hydroxylase
deficiency have severe aldosterone deficiency
and are prone for hyperkalemia especially in
infancy
28. Investigations
• Patients with salt- wasting form are identified
through the measurement of serum
electrolytes, aldosterone, plasma renin and
potassium levels.
29. Diagnosis
• Females of congenital adrenal hyperplasia due
to 21-hydroxylase deficiency are easy to
diagnose in the new born period due to
ambiguous genitalia.
• Males are diagnosed either a few weeks later
due to a salt losing crisis resulting in
dehydration, vomiting, hyponatremia and
hyperkalemia
30. Diagnosis..
• Basal 17- hydroxyprogesterone values
measured by RIA exceeds 10,000 ng/dL in
affected infants, [N 100ng/dL]
31. Diagnosis..
• Fetal DNA testing helps in the prenatal
diagnosis of CAH.
• Maternal treatment with high dose of
dexamethasone can supress excess fetal
androgen production which prevents
ambiguous genitalia .
32. 11- Beta Hydroxylase Deficiency
• Due to mutations of 11- Beta Hydroxylase
• Mineralocorticoid deficiency doesn’t occur
• Females present with ambiguous genitalia
• Boys present with precocious pseudopuberty
33. 17-alpha hydroxylase
• 17 alpha hydroxylase deficiency is a rare cause
of CAH.
• In the absence of 17-alpha hydroxylase
activity, there exists an obstruction to cortisol
and sex hormones biosynthesis
34. 3-β OHSD
• This is a non P450 enzyme that converts
delta(5) to delta(4) steroids.
• Gonads share this pathways with the adrenal
glands.
• Male fetuses are undervirilised as a result of
deficient testosterone production.
35. Treatment
• Patients with 21- alpha hydroxylase deficiency
CAH, aldosterone is replaced with oral
fludrocortisone.
• Adequacy is assessed by patients BP and renin
estimation
• Effectiveness of treatment is judged on the basis
of the presence or absence of normal linear
growth and suppression of 17-OHP and
androgens