final Flashcards

Question

inborn errors of metabolism: maple sugar urine ds

Answer 1

- autosomal recessive - impaired breakdown of branched-chain amino acids (BCAAs) due to a deficiency in the branched-chain alpha-ketoacid dehydrogenase complex = accumulation of KETOACIDS (Leucine, isoleucine, valine) -> sweet odor urine sx: - sweet odor - poor feeding at 1 wk - seizures, coma, death (most die within 1st month of life with no intervention) dx: elevation of branched chain AA, genetic testing for confirmation\ tx: -Leucine restriction and avoidance of catabolism - Infant formulas deficient in branched-chain amino acids must be supplemented with normal foods for growth - Very high leucine levels require hemodialysis - Liver transplant corrects the disorder

Answer 2

* Congenital occurs in 1:3000-1:4000 infants, mostly sporadic from hypoplasia or aplasia of thyroid gland/failure to migrate to normal anatomic location****** * Acquired usually is the result of chronic lymphocytic (Hashimoto) thyroiditis Clinical Manifestations * Congenital: Most newborns appear normal, jaundice may be present * Acquired: Poor linear growth, delayed bone age/dental eruption, skin changes (dry, coarse, brittle), hair loss, lateral thinning of eyebrows, neurological findings (hypotonia, slow relaxation of DTRs), physical and mental sluggishness, nonpitting myxedema, constipation, cold temperature intolerance, bradycardia, delayed puberty * Enzymatic defects/Hashimoto’s: Thyroid enlargement Laboratory findings: * Primary: TSH elevated, total T4/FT4 normal/decreased * Autoantibodies to thyroid peroxidase and/or thyroglobulin possible * Central: TSH normal, total T4/FT4 decreased * Imaging: Thyroid imaging unnecessary, bone age delayed, cardiomegaly common * Screening: All newborns screened shortly following birth, treatment started asap (otherwise, associated with intellectual impairment) Treatment * Synthetic T4/levothyroxine (75-100 mcg/m^2/day) with monitoring of TFTs for response

Answer 3

* Most cases due to GRAVES disease (antibodies directed at TSH receptor, which stimulates TH production) * Other causes: Thyroiditis, thyroid nodules, TSH-producing tumors, McCune-Albright syndrome, exogenous TH excess, acute iodine exposure Clinical Manifestations * F > M, occurs during adolescence, course may be cyclic * Symptoms: Poor concentration, hyperactivity, fatigue, emotional lability, personality disturbance, insomnia, weight loss, palpitations, heat intolerance, increased perspiration, increased stool frequency, polyuria, and irregular menses * Signs: Tachycardia, HTN, increased pulse pressure, tremor, proximal muscle weakness, moist/warm skin, accelerated growth/development, diffuse/firm goiter, thyroid bruit/thrill, exophthalmos * Thyroid storm: Fever, cardiac failure, emesis, and delirium > coma/death Laboratory findings * TSH suppressed; T4, FT4, T3, and FT3 are elevated * TSH receptor-binding antibodies are usually elevated * Presence of TSI or thyroid eye disease confirms Graves * Imaging * Radioactive iodine uptake increased in Graves disease, decreased in subacute/chronic thyroiditis; autonomous hyperfunctioning nodules take up iodine (hot nodules) * Advanced bone age, premature fusion of cranial sutures, osteoporosis (long-standing) Tx: * Avoidance of strenuous physical activity due to concern for cardiovascular instability * Medical: * B-Adrenergic blocking agents: Atenolol (B1-specific/cardioselective), propranolol (decreases conversion of T4 to active T3; used in severe cases/thyrotoxicosis) * Antithyroid agents (methimazole) * Frequently used in initial management of childhood hyperthyroidism * Interfere with TH synthesis * Take several weeks to generate a clinical response * Initial dose: 10-60 mg/day (0.5-1 mg/kg/day) QD (until FT4 and T4 have normalized and signs/symptoms subside) * Maintenance of 10-15 mg/day x 2 years with trial of medication thereafter * If medical therapy unsuccessful, more definitive therapy, such as thyroidectomy or radioiodine ablation considered

Answer 4

-Decreased growth velocity and delayed skeletal maturation in absence of other explanations -May be congenital, genetic, or acquired -Idiopathic is MC -Infantile GHD: Normal birthweight and slightly reduced length, hypoglycemia (with adrenal insufficiency), micropenis (with gonadotropin deficiency), and conjugated hyperbilirubinemia -Dx- clinical and lab evidence -Labs: Serum IGF-1 gives reasonable estimations of GH secretion and action -MRI of hypothalamus/pituitary gland to evaluate for tumor

Answer 5

-dwarfism -Autosomal dominant transmission -Upper arms and thighs are proportionately shorter than forearms/legs -Skeletal dysplasia -Height measurements for screening -Bowing of extremities, waddling gait, limited ROM, relaxation of ligaments, short stubby fingers, frontal bossing, midface hypoplasia, otolaryngeal dysfunction, moderate hydrocephalus, depressed nasal bridge, lumbar lordosis -Imaging: -Short, thick, tubular bones and irregular epiphyseal plates -Ends of bones are thick, with broadening and cupping -Delayed epiphyseal ossification -Narrowed spinal canal (diminished growth of pedicles) -Tx: Growth hormone

Answer 6

-Polyuria, polydipsia, and wt loss -Heavy diaper in a dehydrated child w/o diarrhea -> alarm -Labs: -HbA1c does not rule out dx (less sensitive than blood glucose) -Tx: -Aim for lowest HbA1c w/o severe hypoglycemia or frequent, moderate hypoglycemia -Diet/exercise: At least 60 mins of daily aerobic exercise with bone/muscle strength training at least 3 days/week

Answer 7

* Venous blood pH < 7.30, or bicarbonate < 15 mEq/L and blood B-hydroxybutyrate > 3 mmol/L, or moderate to large ketonuria * Mild: 7.2-7.29/10-14 mEq/L * Moderate: 7.10-7.19/5-9 mEq/L * Severe: < 7.10/<5 mEq/L * ICU monitoring * DKA: Abdominal pain, nausea, vomiting (flu-like, gastroenteritis, acute abdomen); mild-moderate dehydration (5-10%); Kussmaul respirations; progressively somnolent and obtunded Treatment: * Restoration of fluid volume * Inhibition of lipolysis and return to glucose utilization (insulin) * Replacement of electrolytes (sodium and potassium) * Correction of acidosis (spontaneous correction)

Answer 8

* Hyperglycemia > 600 mg/dL and hyperosmolarity > 320 mOsm/kg * Typically, little to no ketosis and no acidosis * Clinical Manifestations: Profound mental status changes (combativeness to coma), seizures, rhabdomyolysis * Similar treatment to DKA with close ICU monitoring * Longer term complications: HTN, lipid abnormalities, nephropathy, retinopathy, neuropathy (more so with T2D)

Answer 9

-Monitor glucose at least 4x/day -> 7-10 for optimal management -CGM- Subcutaneous glucose measured q 1-5 mins -Subcutaneous may lag behind blood glucose if rapid change, so finger sticks still recommended for tx and monitoring of recovery from hypoglycemia -New onset- long acting insulin for basal level // rapid acting analog for mealtime dosing -peak dose @ 1 wk and then decrease it slightly –Pre-pubertal: Higher rate early in night -Post-pubertal: Higher rates early in morning – “dawn phenomenon”

Answer 10

-onset of 2ndary sexual characteristics before 8yo in Caucasian girls -7yo for African American and Hispanic girls -Central PP: Idiopathic or 2ndary to a CNS abnormality that disrupts prepubertal restraint on the GnRH pulse generator -Abnormalities include hypothalamic hamartomas, CNS tumors, cranial irradiation, hydrocephalus, and trauma -Peripheral PP (GnRH-independent): Ovarian/adrenal tumors, ovarian cysts, late-onset congenital adrenal hyperplasia, McCune-Albright syndrome, or exposure to exogenous estrogen -starts with breast development -> pubic hair -> menarche -PPP: -!Ovarian cysts/tumors usually with signs of estrogen excess: Breast development, vaginal discharge, vaginal bleeding -!Adrenal tumors and CAH with signs of androgen excess: Pubic hair, axillary hair, acne, and increased body odor -Accelerated growth/maturation; skeletal maturation quicker than linear growth = compromised adult stature

Answer 11

-Labs: -CPP: Random FSH and LH may confirm dx -PPP: LH response to GnRH is suppressed by autonomously secreted gonadal steroids -Estradiol levels, androgen levels (testosterone, androstenedione, dehydroepiandosterone sulfate), and 17-hydroxyprogesterone should be measured -Imaging: -Bone age (L hand and wrist) -CPP: MRI of brain for CNS lesions -PPP: Imaging of ovaries and/or adrenal gland -Tx: -CPP: GnRH analogues that downregulate pituitary GnRH receptors -Leuprolide (IM injections), histrelin subdermal implant (replaced annually) -After stopping therapy, pubertal progression resumes, and ovulation and pregnancy have been documented -PPP: Dependent on underlying cause -Regardless of cause, attention to the psychological needs of the patient and family is essential

Answer 12

-Primary hypogonadism: Primary abnormality of ovaries -!!!MCC is Turner syndrome -Central hypogonadism: Hypothalamic or pituitary deficiency of GnRH or FSH/LH -Functional (reversible): Stress, undernutrition, prolactinemia, excessive exercise, or chronic illness -Permanent: Congenital hypopituitarism, CNS tumors, or cranial irradiation -H&P, BONE AGE: -Low bone age (< 12 years): -abn growth rate! -Bone age > 12 years: -FSH/LH distinguishes between primary ovarian failure (elevated FSH/LH) and central hypogonadism (low FSH/LH) -Cranial MRI for central -GIRLS W/ ADEQUATE BREAST DEVELOPMENT AND AMENORRHEA: -Progesterone challenge to determine if sufficient estrogen is being produced and to evaluate for anatomical defects -Producing estrogen: Withdrawal bleeding 5-10 days of PO progesterone -> !!MCC of amenorrhea in this case is PCOS -Estrogen-deficient/anatomical defect: No bleeding -Tx: -Replacement therapy in hypogonadal: Estrogen alone @ lowest available dosage -increased slowly then 18-24 months later -> add progesterone -Unopposed estrogen = endometrial hyperplasia

Answer 13

-2ndary sexual characteristics before 9yo -Pubic hair -> penile enlargement -> scrotal maturation, axillary hair, voice deepening, increased growth velocity -CPP: Testes enlarge -PPP: Testes remain much smaller than expected for degree of virilization -Labs: -Elevated testosterone levels -CPP: High LH/FSH -PPP: Low LH/FSH -> CAH: Adrenal androgens and 17-hydroxyprogesterone will be elevated -Imaging: -Bone age -CPP: Brain MRI -PPP: Rule out hepatic, adrenal, and testicular tumors -Tx: -CPP: GnRH analogues/tx of underlying cause -PPP: Steroid synthesis blockers (ketoconazole) or combination of antiandrogens (spironolactone) and aromatase inhibitors (anastrozole or letrozole) that block conversion of testosterone to estrogen

Answer 14

-No 2ndary sexual characteristics by 14yo or if >5 years since first signs of puberty w/o completion of genital growth -!!!!MCC is constitutional growth delay -Hypogonadism may be primary or central -Primary: Testicular insufficiency/anorchia, Klinefelter syndrome/sex chromosome anomalies, enzymatic defects in testosterone synthesis, inflammation/destruction of tests following infection, autoimmune disorders, radiation, trauma -Central: Deficiencies in pituitary/hypothalamic function (same as girls) -H&P, bone age: -Low bone age relative to chronological age + normal growth velocity (prepubertal) -> constitutional growth delay -Bone age > 12 years -Elevated LH/FSH: Primary hypogonadism or testicular failure -Low LH/FSH: Central hypogonadism -Tx: -4-6-month course of low-dose depot testosterone to promote virilization and possibly “jump-start” endogenous development

Answer 15

-<1yo -> VUR -> self limited -Newborns/infants: Fever, hypothermia, jaundice, poor feeding, irritability, vomiting, FTT, sepsis; strong, foul-smelling urine -Preschool children: Abdominal/flank pain, vomiting, fever, urinary frequency, dysuria, urgency, enuresis -School-aged children: -Signs of cystitis: Frequency, dysuria, urgency -Signs of pyelonephritis: Fever, vomiting, flank pain -CVAT is unusual -Physical: BP, abdominal, GU exam -DX: -!!!Most have negative nitrites (70%) -Urine cx is gold standard (properly collected) -Toilet-trained: Midstream, clean-catch specimen -Infants/younger children: Bladder catheterization or suprapubic collection -Bagged specimens only for screening (if negative) -!Positive results: -SPT: Any growth -Catheterization: > 50K cfu/mL -Clean-catch: > 100K cfu/mL -Renal US in all infants after first febrile UTI

Answer 16

* Various types with similar manifestations: Hematuria, urinary RBC casts, HTN, and edema * Hematuria may be microscopic or gross (coffee- or tea-colored) * Protein excretion may be normal (Pr/Cr ratio < 0.2) to nephrotic (Pr/Cr ratio > 2) * Edema (periorbital, facial, extremities, ascites) occurs due to salt and water retention with impaired glomerular function > HTN (glomerular inflammation and renin production) * Require evaluation of BP, renal function, serum albumin, urine protein excretion, C3 levels (to differentiate most likely cause), renal bx Dx: * Diagnosis of acute poststreptococcal GN is supported by recent infection within preceding 7-14 days (MC with GABHS) * If positive culture is not available > infection may be supported by elevated titer of antistreptococcal antibodies (ASO) * Associated with depressed serum C3 complement and normal C4 * Manifestations range from asymptomatic microhematuria to gross hematuria with nephrotic range proteinuria and AKI tx: * No specific treatment * Antibiotic therapy if active infection documented * BP monitoring * Edema: Reduction in salt intake, diuretics, or CCBs * Renal failure: HD or peritoneal dialysis * In most cases, full recovery occurs and complement levels return to normal in 6-8 weeks, microscopic hematuria may persist for as long as a year ## Footnote - [ ] -glomerulonephritis- MC associated with: GROUP A STREP PHARYNGITIS or ime

Answer 17

* MC glomerular cause of acute renal failure in childhood * Diarrhea-associated form (typical form) is usually the result of infection with Shiga toxin-producing strains of shigella or E. coli – MC pathogen is E. coli O157:H7 * Ingestion of undercooked ground beef/unpasteurized foods is a common source * Bloody diarrhea is the usual presenting complaint, followed by hemolysis, thrombocytopenia, and renal failure * Toxin > endothelial damage > platelet deposition/consumption > microvascular occlusion with subsequent hemolysis Clinical Manifestations: * Prodrome of abdominal pain, diarrhea, and vomiting > then, oliguria, pallor, and bleeding manifestations (GI) * Anemia may be profound * Shistocytes (RBC fragments) seen on blood smears * High reticulocyte count, increased LDH, low haptoglobin (consistent with hemolysis) * Severe thrombocytopenia * Hematuria and proteinuria often present Complications * Acute kidney injury * Seizures, PRES from hyponatremia, HTN, or CNS vascular disease * Thrombosis from endothelial damage (despite thrombocytopenia) Treatment * Attention to fluid and electrolyte status is critical * No antimotility or antibiotic agents! * May worsen release of Shiga toxin * Timely dialysis improves prognosis * RBC transfusions often necessary (EPO may reduce this need) Prognosis * Most children recover from acute episode within 2-3 weeks * Residual renal disease (HTN, proteinuria, CRI) in 30% * End-stage renal failure in 15% * Overall mortality (with CNS or cardiac complications) 3-5%

Answer 18

* MC cause is minimal change disease (MCD) in children * MCD: Minimal changes noted with light microscopy, effacement of podocytes on electron microscopy * Other causes: Focal segmental glomerulosclerosis (FSGS) and membranous nephropathy Clinical Manifestations: * Affected patients generally younger than 10 years at onset * Typically, periorbital swelling and oliguria are noted > within several days, increasing edema (possibly anasarca) evident > dyspnea/massive ascites may occur * Urine sediment usually normal * Gross hematuria more common with FSGS than MCD * Plasma albumin low > lipid levels increased (increased hepatic lipogenesis) * Complications: Infections, hypercoagulability, HTN, renal insufficiency Treatment: Corticosteroids, QD x 6 weeks (tapered) * May add calcineurin inhibitor (tacrolimus) or mycophenolate mofetil to achieve steroid discontinuance while maintaining remission * Goal is disappearance of proteinuria * No response > renal bx for further evaluation *

Answer 19

Normal genitalia: - bipotential genitals - Internal and external genitalia formed between 6 and 13 weeks gestation - will develop into female genitalia unless SRY gene present - SRY gene (Y chromosome) → testes → testosterone → DHT via 5α-reductase. ambigious 46, XX: - due to presence of EXCESSIVE ANDROGENS during the critical period of development = masculinization - MCC: congenitial virulizing adrenal hyperplasia (CAH)**; ↑ ACTH → adrenal hyperplasia → ↑ androgens ambigious 46, XY: - due to RELATIVE DEFICIENCY OF TESTOSTERONE PRODUCTION OR ACTION - androgen resistance/androgen insensitivity syndrome: female external genitalia with short vagina, normal formed testes, at puberty - Breast development without growth of pubic, facial, or axillary hair or the occurrence of menstruation (estrogen unopposed by androgen) - 5a-reductase deficiency: Presents at birth with predominantly female phenotype or with ambiguous genitalia ; At puberty: Secondary male sexual development occurs

Answer 20

Diagnosis * First step: Determine whether findings represent virilization of genetic female (androgen excess) or underdevelopment of genetic male (androgen deficiency) * Virilized females: * Most have CAH; 90% of these females with 21-hydroxylase deficiency * Diagnosis made by measuring plasma concentration of 17-hydroxyprogesterone and androstenedione (typically 100 x normal) * Underdeveloped males: * Adrenal hyperplasia with defects in androgen production of testes, excessive ACTH secretion > elevated levels of adrenal steroid precursors * Limited to testosterone biosynthesis: Measurement of testosterone and precursors in basal state + after stimulation by HCG * Normal levels of testosterone: Androgen resistance or interruption of normal morphogenesis of genitalia Treatment * Hormone replacement: Cortisol (adrenal hyperplasia), testosterone * Surgical restoration * Psychologic support of family * ## Footnote Goal is rapid identification of any life-threatening disorders Classic approach to sex assignment has been based on feasibility of genital reconstruction and potential fertility, but effects of prenatal androgen must be considered Recommended to wait until child can be part of the dialogue regarding gender identity and reconstruction when appropriate Treatment should be individualized and managed by a team

Answer 21

* In 90% of uncircumcised males, foreskin should be retractable by adolescence * Prior to adolescence, prepuce may normally be tight and does not require treatment * Following this age: * Inability to retract prepuce > phimosis * May be congenital or result of inflammation * Rarely symptomatic * Treatment: * Reassurance (loosening of prepuce by puberty) * Topical steroid if needed * If narrowing is severe > gentle stretching * Circumcision reserved for most severe cases * Paraphimosis: Prepuce retracted behind coronal sulcus, cannot resume normal position > causes swelling of the glans/pain (venous stasis) Treatment: * When discovered early: Retraction of foreskin may be possible with lubrication * In some cases, circumcision may be needed *

Answer 22

* Abnormal collection of serous fluid between the two layers of the tunica vaginalis of testis (congenital or acquired) * Etiology * Connection of peritoneal cavity through patent processes vaginalis (congenital) * MC cause in children * Excessive production of fluid (secondary) * Defective absorption of fluid * Interference with lymphatic drainage of scrotal structures * Clinical Manifestations * Painless scrotal swelling with transillumination and fluctuance * Congenital hydroceles tend to be intermittent, disappearing when lying supine (drainage of fluid back to peritoneum) * Imaging * US: Anechoic or echolucent area surrounding testes * Duplex US: Differentiates hydrocele from torsion versus epididymitis * AXR: Rule out inguinal hernia * Treatment * Typically, spontaneously resolve within first year of life (congenital) * Surgery is treatment of choice (hydrocelectomy) * Aspiration (fluid usually always accumulates again in short term)

Answer 23

* Twisting of ovary over supportive ligaments of adnexa > venous congestion, edema, compression of arteries > loss of blood flow to ovaries > necrosis, loss of ovary, infertility * Main risk factor is an ovarian mass > 5 cm * Clinical Manifestations * Lower abdominal/pelvic pain, +/- N/V * Infants may have feeding intolerance/irritability * Physical: +/- abdominal TTP, possible palpable mass * Guarding, rigidity, rebound > possible necrosis * Imaging: Doppler US (transvaginal, pelvic) * Ovarian edema, abnormal ovarian blood flow, relative enlargement of ovary * Definitive diagnosis during surgery with direct visualization Treatment: Surgical detorsion * Ovaries functional in 90% of patients following detorsion *

final Flashcards

(48 cards)