Transcript CASE PRESENTATION

CASE PRESENTATION
By: Patricia Baile
September 16, 2009
Patient is a NB baby boy with weak cry
Birth History
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Patient born PT at 34 weeks
NSVD
Birth Weight: 2050g
APGAR 7,8
Maternal History
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28 year old G1P0
Regular PNCU
Negative serologic studies
No known medical condition
No HTN, no DM
Denies smoking, alcohol, drug use
No medication use
Family History
• No known medical condition
Pertinent PE Findings
• GS: hypertonic and irritable, with weak cry
• HEENT: +hypertelorism, jaw held tightly
closed even during crying, no cleft lip or palate
• C/L: SCE, no retraction, CTA
• CV: RRR, + gr 3/6 holosystolic murmur, LPSB
4th ICS, full and equal pulses on all extremities,
good perfusion
Pertinent PE Findings
• Abdomen: benign
• Extremities: hypertonic extremities
Labs
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CBC: WNL
CMP: WNL except Ca
Ca: 6.0 mg/dL
P: 9.2 mg/dL (4.5-9.0)
Mg: 1.5 mEq/L (1.3-2.0)
PTH: 44 pg/mL (N 40-100)
Ancillary Tests
• 2D Echo reveals a small VSD
• Hypoplastic thymus
• FISH study for deletions on chromosme
22q11.2 was negative
Problem List
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Hypocalcemia
Hypoparathyroidism
VSD
Hypoplastic thymus
Clinical Course
• Patient stayed in NICU for 5 weeks because of
difficulty feeding and persistent hypocalcemia
• Currently receiving supplementary Ca and
Vitamin D
HYPOCALCEMIA
Definition of Hypocalcemia
• Total serum Ca less than:
– 7.0 mg/dL in Preterm infants
– 8.0 mg/dL in Term newborns
– 8.8 mg/dL in children
Pathogenesis
• Ca is the most abundant mineral in the body
– 99% in bone, 1% in ECF
– 50% of serum Ca is ionized and considered active
– 40% bound to protein (albumin)
– 10% in chelated form
Hormonal Regulation
Clinical Manifestations
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Neuromuscular excitability
Tetany
Seizures
Stridor or cyanosis from laryngospasm
Hypotension
Impaired cardiac contractility
Work up
• PTH
• Vitamin D metabolites
(calcidiol and calcitriol)
• Total Ca
• Ionized Ca
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Phosphorus
Liver function
Renal function
Magnesium
Hypocalcemia in Neonatal Period
• Early Onset: refers to the first few days after
birth
– Usually seen in preterm babies, neonates stressed
from asphyxia or sepsis, or by being infants of a
diabetic mother
• Late onset: occurs after the fifth postnatal day
– Often related to immaturity of parathyroid glands,
dietary phosphate loading, or hypomagnesemia
Childhood Hypocalcemia
• Vitamin D-related
– Vitamin D-deficient rickets
– Vitamin D-dependent rickets type 1 and type II
• PTH-related
– Hypoparathyroidism
– pseudohypoparathyroidism
Childhood Hypocalcemia
• Calcium/Phosphorus-related
– Malabsorption
– Hyperphosphatemia
• Organ-related
– Hepatic rickets
– Acute pancreatitis
– Renal osteodystrophy
Chronic causes of Hypocalcemia
• Disorders involving PTH
– Hypoparathyroidism
– Pseudohypoparathyroidism
• Disorders related to vitamin D
– Lack of exposure ot UVB radiation
– Inadequate intake
– Fat malabsorption
– Lack of liver activity to promote 25-hydroxylation
– Genetic deficiency of renal 1-alpha-hydroxylase
Management
• IV bolus infusion of 20mg/kg elemental Ca
over 10-20 mins with careful cardiac
monitoring
• Continuous infusion
– Neonates: 500mg/kg 10% Ca gluconate over 24h
– Children: 200mg/kg/24h
DI GEORGE SYNDROME
DiGeorge Syndrome
• Congenital immunodeficiency characterized by
abnormal facies; congenital heart defects;
hypoparathyroidism with hypocalcemia;
cognitive, behavioral, and psychiatric problems;
and increased susceptibility to infections
• Pathological hallmarks include conotruncal
abnormalities and absence or hypoplasia of
thymus and parathyroid glands
• Constellation of defects is not a syndrome
resulting from a single cause, but rather the
failure of an embryological field to develop
normally  DiGeorge Anomaly
Pathophysiology
• Characterized by malformations attributed to
abnormal development of pharyngeal arches
and pouches
• Common thread among organs involved in
DiGeorge anomaly is that their development
depends on migration of neural crest cells to
the region of pharyngeal pouches
22q11.2 deletion
• Mechanism of deletion has been linked to low
copy number repeats (LCRs)
• An aberrant unequal, interchromosomal
meiotic exchange is the dominant mechanism
22q11.2 deletion
• 30-50 genes present within the commonly
deleted region of chromosome 22q11.2
• TBX1 is the gene mainly responsible for the
phenotypic features
– Important in cardiac development
– Expressed in pharyngeal mesenchyme and
endodermal pouch
– Also expressed in the region that gives rise to the
mesenchyme of the brain
History
• Genetic
– Reported to be inherited in AD, AR and X-linked
fashions
– Approx 17% of patients with phenotypic features
of DiGeorge anomaly have no detectable genomic
deletion
History / Manifestations
• Exposure history to alcohol and other toxins
like isotretinoin
• Endocrine
– Hypoparathyroidism leading to hypocalcemia
(observed in 60% of patients)
History / Manifestations
• Cardiac
– TOF: 17%
– VSD: 14%
– Interrupted aortic arch: 14%
– Pulmonary atresia: 10%
– Truncus arteriosus: 9%
History / Manifestations
• Immunologic
– Thymic hypoplasia or aplasia leading to defective Tcell function
– Partial DiGeorge: below-normal proliferative
response to mitogens
– Complete DiGeorge: no T-cell response to
mitogens
History / Manifestations
• Other Manifestations
– Growth retardation
– Behavioral and psychiatric problems
– Neurologic abnormalities
– GU malformation
– Eczema
History / Manifestations
• Infectious
– Increased susceptibility to infections caused by
organisms typically associated with T-cell
dysfunction
– Systemic fungal infections
– Pneumocystis jiroveci
– Disseminated viral infections
Physical Manifestations
• Facies:
– Hypertelorism
– Micrognathia
– Short philtrum with fish-mouth appearance
– Telecanthus with short palpebral fissures
Physical Manifestations
• Otolaryngic
– Low-set ears, often with defective pinna
– Cleft palate
– Submucous cleft
– Velopharyngeal insufficiency
Differential Diagnoses
• Include all 22q11 deletion syndromes and
exposure to teratogens during pregnancy
Differential Diagnoses
• Velocardiofacial syndromes (VCFS or
Shprintzen syndrome)
• Conotruncal anomaly face syndrome
• Cayler syndrome
• Opitz-GBBB syndrome
• CHARGE syndrome
Laboratory Studies
• Fluorescent in situ hybridization (FISH) to
detect deletion of chromosome 22q11.2
• PCR
• Who to screen:
– Neonatal hypocalcemia
– Interrupted aortic arch
– Velopharyngeal insufficiency
– Pulmonary atresia
Laboratory Studies
• Assessment of Immune System
– In vitro studies of T cell function
– Flow cytometry to estimate number of T cells in
peripheral blood and the proliferative responses
to mitogens and antigens
– Lymphocyte phenotyping and stimulation tests
• Assessment of parathyroid function
Imaging Studies
• Lateral-view CXR
• MRI
• 2D Echocardiography
Treatment
• Endocrine
– Hypoparathyroidism and hypocalcemia are
managed with Ca supplements and vitamin D
administration
• Cardiac
– Surgical intervention as necessary
Treatment
• Immunodeficiency
– Prophylactic regimens for T and B cell deficiency
– Transplantation of HLA-identical bone marrow
– Thymus transplantation
Questions???
Thank you 