Case Report

Prenatal Sonographic Findings in a

Case of Wolman’s Disease

Matthew J. Blitz, MD, MBA ,1 Burton Rochelson, MD,1 Monica Sood, MD,2
Martin G. Bialer, MD,3 Nidhi Vohra, MD1

1
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology,
Hofstra Northwell School of Medicine, North Shore University Hospital, Manhasset, NY
2
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology,
Kaiser Permanente, Walnut Creek Medical Center, Walnut, CA
3
Division of Medical Genetics, Department of Pediatrics, Hofstra Northwell School of Medicine,
Cohen Children’s Medical Center of New York, New Hyde Park, NY

Received 14 December 2016; accepted 4 March 2017

ABSTRACT: No published case of Wolman’s disease
has described the prenatal sonographic findings. We
present a case in which a third-trimester sonographic
examination demonstrated fetal hepatomegaly and
bilateral adrenal echogenicity suggestive of diffuse cal-
cification. Wolman’s disease, also known as lysosomal
acid lipase (LIPA) deficiency, is a rare autosomal-
recessive disorder characterized by complete absence
of the LIPA enzyme. The diagnosis of Wolman’s dis-
ease was made postnatally by biochemical testing,
which indicated absence of LIPA enzyme activity and
gene sequencing, which confirmed homozygosity for
the G66V mutation within the LIPA gene. V C 2017 Wiley
Periodicals, Inc. J Clin Ultrasound 46:66–68, 2018; Pub-
lished online in Wiley Online Library (wileyonlineli-
brary.com). DOI: 10.1002/jcu.22481
Keywords: Wolman’s disease; lysosomal acid lipase
deficiency; adrenal glands; ultrasound; obstetrics
INTRODUCTION
W olman’s disease (WD), also known as lyso-
somal acid lipase (LIPA) deficiency, is a
rare disorder characterized by complete absence
of the LIPA enzyme.1 It is thought to occur in
approximately 1 in 350,000 newborns worldwide
and has an autosomal-recessive inheritance pat-
tern. In the Iranian-Jewish population, as many
as 1 in 4,200 newborns may be affected.2 The
Correspondence to. M. J. Blitz
C 2017 Wiley Periodicals, Inc.
V fluid volume was normal, and there were no
66
inability to catalyze the hydrolysis of cholesterol
esters and triglycerides results in massive accu-
mulation of lysosomal esterified lipids through-
out the body, including the liver, spleen, bone
marrow, and gut.3 Until recently, there was no
treatment for WD. Clinical management was
largely supportive and survival beyond 1 year
of age was rare. A literature search revealed no
published cases describing the prenatal sono-
graphic (US) findings of this condition. We pre-
sent a case in which a fetus was found to have
hepatomegaly and bilateral echogenic adrenal
glands suggestive of diffuse calcification on a
third-trimester US examination.
CASE REPORT
A healthy, multiparous woman of Iranian-
Jewish ancestry was found to have a female
fetus with bilateral echogenic adrenal glands
(Figure 1) and hepatomegaly (Figure 2) on US
examination at 34 weeks. Sonography was per-
formed using a Voluson 730 system (GE Health-
care, Milwaukee, WI) with a 3.5-MHz convex-
array transducer. The fetal biometry was con-
cordant with gestational age. Pyelectasis was
noted with the right renal pelvis measuring
approximately 8 mm. The sizes of both kidneys
and of the echogenic adrenal glands were with-
in normal limits. The enlarged liver had a maxi-
mum length of 6.8 cm, which is greater than the
95th percentile for the gestational age. Amniotic
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 PRENATAL US FINDINGS IN WOLMAN’S DISEASE
FIGURE 1. Prenatal sonographic examination at 34 weeks of gestational age. Sagittal sonograms of the fetal abdomen show the right (A) and left
(B) echogenic adrenal glands with posterior acoustic shadowing.
FIGURE 2. Sagittal sonogram of the fetal abdomen shows hepato-
megaly. Maximum liver length measures 6.8 cm, which is greater
than the 95th percentile for the gestational age.
signs of hydrops. Doppler findings of the middle
cerebral artery were normal, and there was no
suggestion of fetal anemia. The comprehensive
US examination performed at 19 weeks had
demonstrated normal fetal anatomy, and the
prenatal course was otherwise uncomplicated.
Neither the patient nor her husband reported
any family history of birth defects, genetic syn-
dromes, mental retardation, recurrent miscar-
riages, or stillbirth. The differential diagnosis
was discussed with the patient and her hus-
band, including the possibility of adrenal hem-
orrhage and neuroblastoma. WD was thought
unlikely due to the rarity of the condition and
the absence of family history. Fetal MRI found
no evidence of adrenal mass or hemorrhage.
Workup for cytomegalovirus and parvovirus
B19 was suggestive of past exposure, and not
indicative of a current or recent infection with
either virus.
VOL. 46, NO. 1, JANUARY 2018
Delivery of the female newborn was by elec-
tive cesarean section at term. Apgar scores
were 9 and 9 at 1 and 5 minutes, respectively.
Renal US on day 2 of life revealed enlarged
adrenal glands bilaterally with diffuse calcifica-
tion of both adrenal cortices. The diagnosis of
WD was made postnatally by biochemical test-
ing, which indicated absence of LIPA enzyme
activity and gene sequencing, which confirmed
homozygosity for the G66V mutation within the
LIPA gene on the long arm of chromosome 10.
The neonate died at 6 months of age secondary
to complications of a bone marrow transplant.
DISCUSSION
Signs and symptoms of WD are usually evident
shortly after birth and consist of abdominal dis-
tention, hepatosplenomegaly, vomiting, diarrhea,
malabsorption, and poor weight gain.4 Additional
findings may include hepatic fibrosis, ascites,
and calcification of the adrenal glands, resulting
in primary adrenal insufficiency. A milder pheno-
type of LIPA deficiency is known as cholesteryl
ester storage disease.5,6 In cholesteryl ester stor-
age disease, there is some residual LIPA enzyme
activity and symptoms may not be apparent
until later in childhood or even adulthood.7
Prenatal diagnosis of WD is possible by chorionic
villus sampling or amniocentesis.8 Both methods
can be used to identify a deficiency in acid esterase
activity in cultured cells or to detect known muta-
tions in the LIPA gene. These invasive procedures
are only performed in pregnancies known to be at
risk for the condition. Similarly, preimplantation
genetic diagnosis can be offered to patients at risk
who undergo in vitro fertilization. In the case pre-
sented here, neither the patient nor her husband
was known to be a carrier for the disease.
67
 BLITZ ET AL
Investigational therapies have included liver
transplantation and hematopoietic stem cell
transplantation, which have prolonged survival
in some cases.9 Sebelipase alfa, a recombinant
form of LIPA, is now offered as enzyme replace-
ment therapy.10 Although this is associated
with a significant prolongation of survival, as
well as a reduction in symptoms and improve-
ments in laboratory parameters, it is not consid-
ered curative.11
US findings in infants diagnosed with WD
have been well described, consisting of hepato-
megaly, splenomegaly, and enlarged, calcified
adrenal glands.12–15 However, based on our
review of the literature, there are no reported
cases of WD in which prenatal US features con-
sistent with the disease are described. The dif-
ferential diagnosis of fetal hepatomegaly and
hepatosplenomegaly is broad and includes
severe isoimmunization, infections, congestive
heart failure, metabolic disorders, neoplasms,
fetal anemia, and Down syndrome. The pres-
ence of bilateral echogenic adrenal glands in a
fetus is very uncommon. Bilateral neuroblasto-
ma and adrenal hemorrhage have been
reported. Intra-adrenal hemorrhage is anechoic
initially and then becomes increasingly echo-
genic over time. Gradually, blood and necrotic
adrenal tissue may be resorbed. Therefore, seri-
al US evaluation may be helpful.
In the absence of an obvious etiology, WD
should be kept in the differential diagnosis of
fetal hepatomegaly and bilateral echogenic
adrenal glands on prenatal US examination.
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