Beckwith-Wiedmann
-Strong positive associations noted between ART and BW
-hypoglycemia, abdominal wall defects, hemihyperplasia, macroglossia, and visceromegaly
-Chromosome 11
-caused by loss of methylation of IC2 on maternal chromosome, paternal uniparental disomy, gain of methylation of maternal chromosome at IC1, and 11p15 paternal duplications.
Acetyl coenzyme A
Mitochondrial oxidative phophorylation is a highly efficient pathway for energy production in living organisms. The first step consists of the oxidation of glucose, amino acids and fatty acids into acetyl coenzyme A. Acetyl co A subsequently enters the Krebs cycle
Dysostosis
Skeletal development is a highly organized process that begins with patterning of the somites and limbs during the third through sixth weeks of gestation. Dysostosis is caused by disruptions of these early patterning processes.
Urea Cycle defect
Encephalopathy with hyperammonemia. The absence of metabolic acidosis at blood gas testing eliminates organic acidemias, pyruvate metabolism defects, and mitochondrial energy defects. A plasma amino acids profile is then necessary to distinguish between urea cycle defects and transient hyperammonemia of the newborn. Transient hyperammonemia is characterized by early (within the first 24 hours after birth) hyperamonemia and a normal plasma amino acid profile, whereas urea cycle defects are characterized by a highly abnormal plasma amino acid profile
Transient neonatal diabetes mellitus
manifest within the first month after birth. Neonates with TNDM classically present with intrauterine growth restriction, failure to thrive, hyperglycemia, and dehydration at age 4 to 6 weeks. TNDM is now recognized as a disorder of genetic imprinting involving chromosome 6
Fragile X
X-linked dominant (FMR1). FMRP production is regulated by CGG trinucleotide repeats in the FMR1 gene, as well as methylation of the gene. CGG expansion leads to decrease dexpression and in the full form (>200 repeats), silencing fo the FMR1 gene. In teh premutaiton state (55-200) will develop the typical clinical picture of fragile X syndrome
-long fascies, strabismus, joint hyperflexibilty, flat feet, macro-orchidism
Trisomy 18
Growth deficiency, microcephaly, short sternum, campodactly, nail hypoplasia, distinctive clenched hand posture, congenital heart defect, renal and genital anomalies
-second most common trisomy after t21
Silver-Russell
IUGR, BW less than 3 SDs below mean, postnatal growth retardation, fifth-finger clinodactyly, triangular face, micrognathia, leg or arm length asymmetry, hypogenitalism, cryptochidism, hypotonia
-Imprinting disorder
Meckel-Gruber
lethal autosomal recessive disorder casued by mutations in genes encoding for protein involved in the structure or function of the primary cilium. Affected patients present with large polycystic kidneys and subsequent pulmonary hypoplasia, postaxial polydactyly, and occipital encephalocele. Developmental hepatic abnormalities have also been described
MPSS - massively parallel shotgun sequencing
allows the sequencing of the whole genome of both the pregnant woman and fetus in a single test. All DNA sequences are then mapped to a reference genome for analysis
-high sensitivities for the detection of fetal aneuploides: 21,18,13, turners
Phenylketonuria
First disorder included in NBS
cffDNA
result of placental cell apoptosis and is found in the maternal circulation of pregnant women. Good for:
-Detection of specific genetic sequences
-Quantitative assessments of cffdna for risk assessment of preeclampsia and aneuploidy
-Analysis of allele ratio for detction of aneuploidy
Lactate
Lactate elevation during NEC is secondary to both tissue necrosis and production of L-lactate, as well as D-lactate production. D-lactate is a lactate isomer produced by enteric bacteria, most labs can’t distinguish them
Next-generation sequencing
The DNA template is broken into millions of fragments that are then ligated to short nucleotide adapters. These adapters include bar codes for easy identification, as well as primers to allow capture of specific gene regions. Once captured, the DNA fragments are amplified, sequened using labeled nucleotides, and compared with a reference sequence.
-Sanger relies on hybridization of the region by using primers
Fatty acid oxidation defect
suspect in infants with abnormally low ketones in the presence of hypoglycemia. Also present with encephalopahty, mild metabolic acidosis with increased lactate level, hepatocellular dysfunction and elevated ammonia levels. Confirmed with acylcarnitine profile abnormailities
Ornithine transcarbamylase
X-linnked. Failure to convert ornithine to citrulline in the urea cycle, leading to hyperammonemia. Affected boys typically present at age 2 to 3 days with hyperammonemia, ecephalopathy, and respiratory alkalosis. girls have variable clinical picture than boys because of random X inactivation
elevated lactate
- Artifactual elevation
2.hypoxia - Inborn error of metabolism.
– organic acidopathy and long-chain fatty acid defects (5 -10).
—Organic acidopathy, such as methylmalonic acidemia, should be suspected when acidosis is out of proportion to lacticemia. Ketoacidosis, hyperammonemia and hypoglycemia. Urine organic acid quant
—Long-chain fatty acid oxidation - high lactate, hypoglycemia, elevated CK, dilated cardiomyopathy and cardiac arrhythmia. An acylcarnitine profile needed - Primary lactic acidosis - pyruvate metabolism and electron transport chain defects (10 - 20)
Cleidocranial dysplasia
large fontanelle and wide sutures. rare autosomal dominant disorder. The presence of clavicle hypoplasia with drooping shoulders, large fontanelle and wide sutures, and midface hypoplasia should raise suspicion in the neonatal period
Glutaric acidemia type 1
autosomal recessive disorder caused by glutaryl-coenzyme A dehydrogenase deficiency. Most patients present in infancy with acute encephalopathy, typically triggered by an ifnection. The resultant striatal injury leads to abnormal posturing, including severe dystonia, opisthotonos, and athetosis. Marocephaly is common in glutaric acidemia type 1 and may be present at birth
Myotonic dystrophy 1
Autosomal dominant disorder that can manifest in teh newborn period with hypotonia, respiratory distress, poor feeding, talipes quinovarus, and eyelid ptosis. It is caused by expansion of trinucleotide CTG repeats in the noncoding region fo the myotonic dystrophy protein kinase gene on chromsome 19. Diagnosis with >50 repeats
Cri du chat
deletion of part of the short arm of chromosome 5. In most cases (85%), the deletion is de novo. In the remaining 15% of cases, a balanced translocation is identified in a parent. Characterized by the following: SGA, microcephaly, round face, hypertelorism, downward slanting palpebral fissures, single palmar crease, characteristic catlike cry secondary to hypotonia and laryngeal abnormalities
Williams syndrome
chromosome 7. deletion of elastin (ELN). - growth restriction, broad forehead, periorbital fullness, long philtrum, wide mouth, supravalvular aortic stenosis, hyperclacemia
Triploidy
69 chromosomes: XXX, XXY, XYY. Triploidy is associated with IUGR, hypotonia, hydrops, and poly or oligo-hydramnios. Single sex chromosome aneuploidies (47 XXX, 47 XXY, 47 XYY) typically assoicated with mild phenotype
Campomelic dysplasia
haploinsufficiency of SOX9.
-short, bowed limbs
-hypoplasia of the scapula and pelvis
-rib and vertebral abnormalities
-craniofacial abnormalities, including Pierre Robin sequence with clef palate
-Disorder of sex development
