Peds Flashcards
inborn errors metabolism
energy metabolism/catabolism-present acutely
intoxication - Sx free then present acutely - urea cycle
complex molecules/anabolism - not acute presentation
Galactosemia
-Galactose-1-P UDT deficiency MCC - classic galactosemia w/ intellectual disability
AR, GALT/GALK/GALE genes ; newborn screen,
-present at birth, vomiting, diarrhea, jaundice; cataracts b/c galactitol
Dx: reducing substances in urine
-Tx: no lactose (can’t break down), no galactose (no cataract, hepatomegaly but still CNS Sx)
PDH deficiency
PDH: oxidative decarboxylation: pyruvate to Co2 + acetyl CoA
-low lactate:pyruvate ratio, elevate lactate ad pyruvate; buildup alanine
-neonatal acidosis, lactic acidosis or present later
ataxia
-can trigger exacerbations by high card meal
-cytic lesions: white matter BG +/- corpus callosum
-MCC X-linked E1 (less common AR)
Tx: acetyl CoA, ketogenic diet, carnitine, coQ10, biotin, acetazolamide-ataxia
NF1
mild developmental delay
-renal A stenosis from renal A dysplasia-> HTN
-pheochromocytoma
-Moyamoya syndrome
-cerebral ansuerysms
-macrocephaly independent of hydrocephalus
-pathologic fracture, scoliosis, sphenoid wing dysplasia
autosomal dominant neurofibromin- chr 17
GLUT-1 deficiency
-low CSF glucose, normal serum glucose
-GLUT1 encoded by SLC2A1 de novo or AD
-epileptic encephalopathy if early, or episode invoultary movements/ataxia, paroxysmal exertional dyskinesias
-Tx: ketogenic diet
Phenylketonuria PKU
Phenylalanine hydroxylase deficiency (phenylalanine to tyrosine); -if tetrahydrobiopterin deficiency (cofactor of phenylalanine hydroxylase)
-accumulate phenylalanine —> metabolized phenylacetic acid causing musty odor
autosomal recessive
-normal at birth after feedingrise phenylalanine levels; early normal Neuro development
-no acute metabolic encephalopathy
-microcephaly, seizures, fair with blond hair/blue eyes - no tyrosine and no melanin pigment production
-avoid phenylalanine
-newborn screen: detects hyperphenylalanemia-high phenylalanine in blood
Dx: reduction phenylalanine in blood and urine after BH4 given
Tx: low protein, phenylalanine free diet
Maple syrup urine disease
autosomal recessive
-branched chain a-ketoacid dehydrogenase complex deficiency (leucine, isoleucine, valine)
-with feeding, present as neonate
Day 2-3 of life - progressive encephalopathy
opisthotonus arched back posture (like an arched tree)
Urine: maple syrup, esp during exacerbations
Tx: low protein diet
X linked disorders
All Oblivious Females Can Pass Her Boys X-Linked Disorders
All-Aicardi (dominant) + X-linked adrenoleukodystrophy
Oblivious-ornithine
transcarbamylase deficiency
Females-Fabry + Fragile X (trinucleotide repeat)
Can-CMT-demyelinating(CMt1 and Tx)
Pass -PDH deficiency (MCC)
Her-Hunter (Hurler AR)
Boys-BPAN-beta propeller protein associated neurodegernation (mostly female)
X-Linked-McLeod’s syndrome-XK disease+ Lesch-Nyhan
Disorders-muscular Dystrophy (Emery-Dreifuss-Emerin mutation, Becker, Duchenne)
Neurulation
Differentiation
Specification
- neuralation (3-6 wks) - Neural plate - ectoderm ->to neural tube via notorcord (mesoderm “make note”)
- Notochord - mesoderm becomes vertebral column
-induces neuralation neural plate - forms midline groove with fusion starting in center,->
by week 4: anterior neuropore then posterior closes
->3. neural tube formed-> differentiation
-ventral: notorcord signals via sonic hedge hog
-dorsal: lateral ectoderm signals - 5-6 wks - Specification: Neural tube->3 vesicle segmentation
-Prosencephalon = telencephalon (cerebral hemispheres) + diencephalon (hypothalamus, thalamus)
-Mesencephalon - midbrain
-Rhombencephalon - pons, medulla, cerebellum
-Specification problem - septa-optic dysplasia
Neural crest cells
PNS , autonomic ganglia+ cromaffin cells adrenal medulla + melanocytes
neural tube defects-anterior
NTD: risk: more common in females, retinoids, VPA, carbamazepine? , hx infant NTD
-supplement 0.4 mg folate
-Dx: prenatal US, alpha-FTP +Achesterase elevated (in serum+amniotic fluid); can get prenatal MRI; if positive screen for trisomy 13 and 18 (encephalocele)
-anencephaly (no cerebral hemispheres, cranial vault b/c no mesoderm diffferentiation), Anterior neuropore prob
-encephalocele (hernation neural tissue into midline skull-occipital (more severe, more common)>frontal; fluntuant mass, can still live but microcephaly) -anterior neuropore
-trisomy 13, 18
Holoprosencephaly:
-no prosencephalon to telencephaphon (cerebral hemispheres + BG+ olfactory) + diencephalon (thalamus+hypothalamus)
-no telencephalon to 2 cerebral hemispheres + BG
-alobar -most severe; vs semilobar vs arrhinecephaly
Holoprosencephaly
Trisomy 13, 18, Sonic HH, cholesterol synthesis (Smith Lemli Opitz-7 dehydrocholesterol reductase)
ALobar- cyclopia, endorine problems, hydrocephalus
semilobar -partial agenesis corpus callosum; splenium + genu preserved)
Arrhinecephaly - agenesis olfactory bulb + tract
-Kallmann’s X linked dominant - anosmia + hypogonadims
neural tube defects - posterior
-meningocele (only leptomeninges, CSF herniate) vs occipital encephalocele ; no neurological deficit vs myelomeningocele
Myelomeningocele - SC, nerve root, meninges protrude, Chiari II ; hydrocephalus, bowel/bladder dysfunction
-sacral agensis- absence sacrum, not sacral SC ; range clinical Sx
-GI, urogenital, SC prob
-maternal IDDM risk
-homeobox gene mutations, AD
Diastematomyelia - splitting SC into 2 by midline septum
-diplomyelia - duplication of SC - two central canals each with gray and white matter like a normal SC (vs diastematomyelia)
Posterior neuropore prob - spina bífida
-occult spinal dysraphism - tuft of hair + neuro dysfxn - tethered cord, epidermoid cysts
spinal bifida occulta - no neuro dysfxn
tuberous sclerosis complex
TSC1 mutation on chromosome 9 or TSC2 mutation on chromosome 16. Tumor suppressor genes. Autosomal dominant, variable expression.
HAMARTOMAS
-Hamartomas in CNS, retina, skin-mulberry lesion
-Angiofibromas ;
-Mitral regurgitation
-Ash-leaf spots +Shagreen patches
-cardiac Rhabdomyoma-can regress over time
(Tuberous sclerosis);
-autosomal dOminant;
-Mental retardation (intellectual disability);
-renal Angiomyolipoma
-Shagreen patches, subependymal giant cell astrocytomas and ungual fibromas.
lymphangiomyomatosis -pulmonary disease in females - dyspnea, hemoptosis, pneumothorax - Tx - tamoxifen-fatal yrs after under; Dx chest imaging
Fabry
only x-linked sphingolipidosis
alpha galactosidase defect
‘Fabry is a gal (galactosidase) who tries ceramics’
(build up of ceremide trihexaside)
Throwing pottery (hands+feet on pedal-small fiber neuropathy) + splatter (angiokeratomas trunk, LE) + round clay clogging arteries->strokes (dolioectatic) + cardiomyopathy + ESRD + cloudy corneals
-ESRD, birefringent lipid deposits, lamellar deposits
Tx: enzyme replacement
