Case Challenge:
Genetics
A 2-Month-Old Female Infant
with Failure to Thrive
Parth Patel, MD; Nikil Swamy, MD; Grigoriy Klimovich, MD; Matthew A. Marcus, MD;
and Robert C. Holleman, MD
A
2-month-old previously healthy
female infant born at full term
presented to the emergency
department with increasing difficulty
breathing for the past 4 days. On triage,
the patient did not have any significant
findings and was sent home on supportive measures. The next day, the patient
was taken to her primary care physician’s
office by her mother for increased difficulty in breathing, increasing fussiness,
decreased feeding, and an episode of nonbilious and nonbloody vomiting. During
that assessment, the pediatrician noted
poor weight gain in the interim since the
prior visit. In the office, the patient was
found to be normothermic, hypertensive,
tachypneic, tachycardic, hypoxic, and
profoundly anemic. The patient was subsequently admitted to the hospital.
Her respiratory status continued to
worsen, so she was transferred to the pediatric intensive care unit. The patient was
subsequently intubated and received supportive measures. There was no known
family history of pulmonary, cardiac,
renal, neurological, or gastrointestinal
problems. The patient lived at home with
her nonconsanguineous parents and they
denied any exposure to toxic chemicals,
pets, or smoke. The patient’s newborn
screenings were normal and immunizations were up to date. Physical exam findings of note were pallor, acute respiratory
distress as evidenced by a right preauricular pit, and sunken anterior fontanelle.
Parth Patel, MD, Nikil Swamy, MD, and
Images courtesy of Parth Patel, BS.
Grigoriy Klimovich, MD, are recent graduates
of the University of South Carolina School of
Medicine. Matthew A. Marcus, MD, is a Pediatric Radiologist, Pitts Radiology, Columbia,
SC. Robert C. Holleman, MD, is a Pediatric Nephrologist, Palmetto Health Richland, Columbia, SC.
Address correspondence to: Nikil Swamy,
MD, University of South Carolina School of
Medicine, Medical Education Campus, 6311
Garners Ferry Road, Columbia, SC 29209;
email: [email protected].
Disclosure: The authors have no relevant financial relationships to disclose.
doi: 10.3928/00904481-20130426-06
PEDIATRIC ANNALS 42:5 | MAY 2013
Figure 1. Sagittal ultrasound view of the patient’s left (a) and right (b) kidneys at day of life 100. The
white arrows in both figures are pointing to the hyperechoic regions of the kidneys, suggesting extensive calcification.
For diagnosis, see page 192
Editor’s note: Each month, this department features a discussion of an unusual diagnosis in genetics, radiology, or dermatology. A description and images are presented,
followed by the diagnosis and an explanation of how the diagnosis was determined. As
always, your comments are welcome via email at [email protected].
Healio.com/Pediatrics | 191
Case Challenge
Diagnosis:
Primary Hyperoxaluria
Causing Cortical
Nephrocalcinosis
The two main types of hyperoxaluria
are primary and secondary. The latter is
usually due to enteric causes. Primary
hyperoxaluria is a very rare autosomal
recessive disease affecting 1 to 2 people
per 1 million, and it may be associated
with severe renal disease early in life.1
In this case, genetic testing confirmed
the diagnosis of primary hyperoxaluria
type I, in which there is a deficiency of
the enzyme alanine-glyoxylate aminotransferase. This enzyme is normally
found in hepatic peroxisomes and is responsible for converting glyoxylate to
glycine. A lack of this enzyme results in
the accumulation of insoluble calcium
oxalate salts in various tissues, including the kidneys (nephrocalcinosis).
Thereafter, end-stage renal disease and
systemic oxalosis ensues.2
Nephrocalcinosis is defined as the deposition of calcium in the parenchyma of
the kidney in either a cortical or medullary distribution. Medullary nephrocalcinosis is much more common than cortical nephrocalcinosis; it usually develops
gradually and is an incidental finding on
radiographs. The differential diagnosis
for cortical nephrocalcinosis includes
acute cortical necrosis, chronic glomerulonephritis, hyperoxaluria, chronic transplant rejection, and Alport’s syndrome.3
Radiographic findings of cortical
nephrocalcinosis include peripheral band
of calcification, parallel tram-track line
calcification, or diffusely distributed
punctuate calcifications representing
calcified cortical glomeruli and tubules.
Sonographically, there is increased echogenicity present, which may produce
acoustic shadowing depending on the
amount of calcification. The degree and
rapidity of cortical nephrocalcinosis is
192 | Healio.com/Pediatrics
Figure 2. Sagittal ultrasound view of the patient’s left and right kidneys at day of life 125. The white
arrows in both figures are pointing to the hyperechoic regions of the kidneys, suggesting extensive
calcification. The calcification has progressed markedly from Figure 1.
Figure 3. Noncontrast computed tomography of the patient’s abdomen at day of life 110. Both renal
cortices (indicated by the white arrows) are hyperdense.
very evident in both Figure 1 (see page
191) and Figure 2. On computed tomography (CT), one will see punctate band
or tram-line calcification in the cortex.
CT is the most sensitive radiographic
modality for detecting nephrocalcinosis.4 In Figure 3, one can see that the
non-contrast CT image shows uniformly
hyperdense renal cortices. On magnetic
resonance imaging (MRI), calcifications
appear hypointense due to signal void-
ing in both T1- and T2-weighted scans.
Hence, minor calcifications are easily
missed on MRI.4,5
A definitive diagnosis of primary hyperoxaluria is made either from genetic
sequence blood testing or liver biopsy in
which enzymatic activity level is measured. The treatment for this condition
involves sequential liver and kidney
transplantation. Kidney transplantation
alone will not be adequate because the
PEDIATRIC ANNALS 42:5 | MAY 2013
Case Challenge
grafted kidney will still be subject to
oxalate deposition.6 Other treatment options include dialysis, decreasing dietary
oxalate consumption, increasing urine
output to minimize oxalate deposition
using thiazide diuretics due to its calcium retaining properties, and, in some
instances, pyridoxine supplementation
to promote normal conversion of glyoxylate to glycine.7
In this case, the patient presented
with profound renal failure and its inherent complications. Upon admission,
the patient was hyperkalemic, hypocalcemic, hyperphosphatemic, and had
pH and HCO3(-) levels of 6.9 and < 5
mEq/L, respectively. The patient’s blood
urea nitrogen and creatinine levels were
162 mg/dL and 13.4 mg/dL, respectively. Based on the method developed
by Schwartz and Work,8 the patient’s
calculated glomerular filtration rate was
1.75 mL/min/1.73 m2. Due to renal failure suggested by lab data and renal ultrasounds, she was placed on dialysis.
PEDIATRIC ANNALS 42:5 | MAY 2013
Thereafter, serum and urine oxalate level
measurements were made. These were
141.1 mcM and 80 mg/day, respectively.
These levels, along with other clinical
data, prompted us to test for primary
hyperoxaluria. This was performed by
DNA sequencing of blood samples. Ultimately, a diagnosis of primary hyperoxaluria type I was made.
CONCLUSION
The rapidity and degree of cortical
nephrocalcinosis prompted us to test
for primary hyperoxaluria. Upon admission, the patient was immediately
placed on dialysis and supportive measures. The patient will soon undergo
sequential liver and kidney transplantation. While awaiting transplantation, the
patient has been placed on an oxalaterestricted diet, thiazide diuretics, and
pyridoxine supplementation, in addition
to dialysis.
Always keep in mind that in an early
infant, rapidly progressing renal failure
with cortical nephrocalcinosis is most
likely a sign of primary hyperoxaluria.
REFERENCES
1. Hoppe B, Langman CB. A United States
survey on diagnosis, treatment, and outcome
of primary hyperoxaluria. Pediatr Nephrol.
2003;18(10):986-991.
2. Hoppe B, Beck BB, Milliner DS. The
primary
hyperoxalurias.
Kidney
Int.
2009;75(12):1264-1271.
3. Kim SH. Radiology Illustrated: Uroradiology, 2nd ed. New York, NY: Springer, 2012.
4. Schepens D, Verswijvel G, Kuypers D, Vanrenterghem Y. Images in nephrology. Renal cortical nephrocalcinosis. Nephrol Dial
Transplant. 2000;15(7):1080-1082.
5. Diallo O, Janssens F, Hall M, Avni EF. Type
1 primary hyperoxaluria in pediatric patients:
renal sonographic patterns. AJR Am J Roentgenol. 2004;183(6):1767-1770.
6. Coulter-Mackie MB, White CT, Hurley RM,
et al. Primary Hyperoxaluria Type I. Available
at: www.ncbi.nlm.nih.gov/books/NBK1283.
Accessed March 4, 2013.
7. Milliner D. Treatment of the primary hyperoxalurias: a new chapter. Kidney Int.
2006;70(70):1198-1200.
8. Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents.
J Am Soc Nephrol. 2009;4(11):1832–1843.
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