Inborn Errors of Metabolism

Board Review 3/7/2013ADOLESCENT (part 1):Adolescent DevelopmentTest QuestionWho remembered that daylight savings is this weekend??I did!Nooooooooo!!!

Pubertal Development:Physical changes

PubertyDevelopmental stage characterized by:Maturation of gametogenesisSecretion of gonadal hormonesDevelopment of secondary sexual characteristics and reproductive functionsPediatricians are constantly faced with questions about what is normal during puberty

Changes in GnRH secretion (increased pulsatility) result in puberty

Normal PubertyAge of onset:Girls: 8-13 yearsThelarche can occur at age 7 in African-American and Mexican American girlsBoys: 9-14 yearsSexual Maturity Rating (SMR)Used to document a childs development through pubertyConsists of inspection of breast, genital, and pubic hair developmentLimitation: does not have specific measurements

Stages of sexual developmentStage 1: prepubertalStage 2: girls: thelarche boys: testicular enlargement (4mL)Stage 3: ongoingStage 4: nearly completeStage 5: adultlike

Pubertal progression from stage 2 to stage 5 can take between 2.5-5 years to complete

Question #1Which is the correct sequence of pubertal events in a female?Menarche thelarche peak height velocity pubarcheThelarche pubarche peak height velocity menarchePubarche thelarche menarche peak height velocityThelarche pubarche menarche peak height velocity

Predictable Progression of PubertyMales:Testicular growth pubarche penile growth peak height velocityTesticular volume < 4mL (2.5cm) is prepubertalReach SMR4 prior to attainment of peak height velocityFemales:Thelarche pubarche peak height velocity menarche Peak height velocity is typically 1 year before menarcheGirls height will typically increase ~6-8cm after menarche has occurred

Question #2A mother brings in her 13 year old son at his request due to his concerns about breast tissue. He has noticed he has a small amount of breast tissue and wants to know if it can be removed. He is otherwise developing appropriately and does well in school. On exam, he is SMR3 for genital growth and pubic hair. You also notice a small amount of breast tissue bilaterally under his nipples. What is the most appropriate course of action?Refer the patient to a plastic surgeonRefer the patient to an endocrinologist for hormone therapyOrder a brain MRI to rule out malignancyReassure the patient that this is a normal part of puberty and follow up in 6 monthsOrder FSH and LH levels

Normal variations in pubertal developmentAsymmetric breast or testicular developmentCan see up to 1 stage advance of unilateral development at onset of pubertyGynecomastia50% of boys will have some degree of breast tissue during pubertyTypically during pubic hair stage 3 or 4Gynecomastia without onset of puberty is concerningLasts less than 1 yearCan just be observed for resolutionLinear growthPeak height velocity in girls occurs earlier chronologically and in pubertal staging than in boysBoys growth spurt is typically 2 years after girlsPeak height velocity is more closely correlated with SMR than chronologic age

Linear GrowthAverage prepubertal height velocity 5-6cm/yrAverage pubertal height velocity:Boys = 9-10cm/yrGirls = 8-9cm/yrCompletion of this growth spurt takes 2-4 yearsLonger period of prepubertal growth and greater pubertal height velocity account for the typical height discrepancy between males and femalesLongitudinal growth chart is much more useful in determining abnormality of growth versus a single point in time

Question #3A boy comes in with his parents for his 12 year old well-child check and wants to know how tall he is going to be. His mother reports that he has been growing but that he is shorter than most of his peers. His mother is 160 cm (63 in) tall and his father is 172 cm (68 in) tall. With the exception of his relative short stature, his medical history is unremarkable. You advise him that the best way to estimate his potential for growth is to calculate his midparental target height and compare it to his current height and his skeletal maturity. Of the following, what is the BEST estimate of his midparental target height?160 cm (63in)165.5cm (65in)172.5cm (68in)177.5cm (70in)182.5cm (72in)Predicting heightHeight is largely determined geneticallyTarget height can be crudely estimated:Average of parents heights in cm+6.5cm for boys-6.5cm for girlsBone age can also be used predict heightBest performed by an endocrinologistKeep in mind a bone age can be off from chronologic age by as much as 2 years and still be normal (ie constitutional growth delay)Timing of puberty: effect on heightThere is a genetic influence on the timing of puberty?autosomal dominantEarlier puberty: will have tall stature during puberty compared to peersWill complete their growth prematurely and have a lower peak adult height than expected Rapid fusion of their growth plates Later puberty: short stature in youth but an adult height that is slightly above expectations Slow but constant prepubertal growth of long bones without rapid maturation of the growth plateTiming of puberty affects both linear growth rate and skeletal maturity

Question #4A mother brings in her 9 year old daughter because she saw some blood in her underwear and is concerned that her daughter has started her period. Menarche for mom was achieved at age 11. On exam, the girl is well appearing with no dysmorphic features or rash. She has SMR stage 1 breast development and no pubic hair development. Of the following, which is MOST likely going to elicit a cause for her vaginal bleeding?Obtaining a bone age radiographPlotting the childs height and weight on a growth chartObtaining serum LH and FSH levelsObtaining a serum estradiol concentrationExamination of the genetalia for a foreign bodyMenarcheGenetic influence on age of menarcheTypically occurs at SMR 4 breast developmentVaginal bleeding at SMR 1-2 is not likely to represent menarche or be hormonally mediatedAverage age of menarche: 12.6 yrsRange: 11-14 yrsAverage time of menarche after thelarche: 2 yrsRange 0.5 5 yrsNo menarche by age 16 warrants investigation

MenarchePhysiologic leukorrhea precedes menses by 3-6 monthsImmature hypothalamic-pituitary-gonadal axis at the beginning of menstruation50% of menstrual cycles are anovulatory in first 2 years after menarcheCan cause menstrual irregularity that is normalQuestion #5 A 15 yo boy comes to the ER because of crampy abdominal pain, diarrhea, and body aches. His siblings also have diarrhea. Exam reveals no icterus or organomegaly, although he has increased bowel sounds and mild diffuse abdominal tenderness. His genetalia are at SMR4. Amount the results of his lab tests are the following: Total bilirubin: 0.6mg/dL ALT: 18U/L Alkaline phosphatase: 460IU/L AST: 22U/LOf the following, what is the MOST likely explanation for these lab results?Physiologic growth spurtBone malignancyInfectious hepatitisInflammatory bowel diseaseViral gastroenteritisEffects of puberty on other body systemsHematocrit increases in males when the growth spurt beingsAfter puberty, males normal Hgb = 14-18g/dLFemales remain lower: 12-15g/dLAlkaline phosphatase can increased during a growth spurtResult of rapid bone growth (high osteoblastic activity)Can be up to 500IU/LCholesterol concentrations peak in early pubertyBlood pressure gradually increasesBased on height, sex, age