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\title{Young female pregnant mother initially treated as viral hepatitis
finally diagnosed and sucessfully treated as Wilson disease~}



\author[1]{Rajan  Bhandari}%
\author[1]{Paribesh Gyawali}%
\author[2]{Shambhu Khanal}%
\author[2]{Shivani Gupta}%
\affil[1]{Department of Internal Medicine, College of Medical Sciences-Teaching Hospital}%
\affil[2]{Department of Internal medicine , Institute of Medicine ,Kathmandu }%


\vspace{-1em}



  
  \date{April 22, 2026}


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Abstract

Successful pregnancy is a rare phenomenon in women with Wilson's disease
(WD).~ We report a case of a primigravid 19 -years old woman who
presented with hemolytic anemia and was later diagnosed with Wilson's
disease for the first time during pregnancy. With prompt treatment, she
delivered a healthy albeit pre-term child.

Keywords: Anemia, Hepatitis, Jaundice, Pregnancy, ~Wilsons disease

\par\null

Consent: ~Written informed consent was obtained from the patient to
publish this report in accordance with the journal's patient consent
policy.

\par\null

\subsubsection*{Introduction}

{\label{introduction}}

Wilson's disease, also known as hepatolenticular degeneration, is an
autosomal recessive disorder of defect in copper transport due to a
mutation in the adenosinetriphosphatase copper transporting beta (ATP7B)
gene. Impaired copper transport results in the accumulation of copper in
the liver, brain, and cornea, thereby causing symptoms. It presents as
liver disease, neurological, neuropsychiatric symptoms, and non-immune
hemolytic anemia~{[}1{]}. Kinnier Wilson first described the disease in
1912. It affects between 1 in 30000 individuals to 1 in 100,000
individuals~{[}1,2{]}. The mean age at diagnosis is 13.2 years~{[}3{]}.
The diagnosis may be overlooked owing to its numerous presentations of
non-specific symptoms of fever, fatigue, and change in behavior to
fulminant hepatic failure. Kayser-Fleischer ring~is found more commonly
with the neurological presentation, up to 95 \% of cases~{[}4{]}.
Hemolytic anemia, which may be seen as a distinctive clinical feature
with jaundice or acute liver failure in Wilson disease, is a rare
presentation in isolation~{[}5{]}. The diagnosis is often based on the
constellation of clinical findings, serum ceruloplasmin, urinary copper
excretion, Coombs negative hemolytic anemia, and liver biopsy~{[}5{]}.

We report a case of a 19 years old pregnant lady who presented for the
first time in her life with Coombs negative hemolytic anemia in the
third trimester of pregnancy.~Jaundice, as a presentation in pregnancy,
can be due to hemolysis with or without hepatitis secondary to Wilson's
disease.

\subsubsection*{Case Presentation}

{\label{case-presentation}}

A 19-year-old normotensive primigravida from a rural area presented to
our center in the third trimester at 30 weeks of gestation with a
history of fever, yellowish discoloration of eyes and urine, malaise,
generalized weakness, and fatigue for ten days. She also had moderate
pain in the upper abdomen, more localized on the right side, decreased
appetite, and a few vomiting episodes.~She received symptomatic care as
she was treated with the diagnosis of acute viral hepatitis in her local
hospital initially. However, she did not have clinical improvement. She
did not have a history of altered sensorium, itching, pale-colored
stools, or bluish patches on the body. She never had any similar illness
in the past. Movement disorders, behavioral and personality changes were
not noted in the past. She had uneventful home delivery and childhood.
She was good at her academic performance and there was no history of any
known liver or neurological disorders in ~family members.

On examination, she had pallor and icterus with no palpable lymph nodes.
She had a fever of the recorded temperature of 101 degree Fahrenheit
with a blood pressure of 100/60 mmHg on bilateral arms . A firm, tender
liver with regular margin and surface, with a distinct border, was
palpable 4 cm below the right subcostal margin. The fundal height of the
patient corresponded to 28 weeks of gestation. Fetal heart sound was
audible, and the rest of the systemic examinations had normal findings.

Her hemoglobin was 5 g/dl on the initial presentation at the district
hospital, where she was transfused 2 pints of fresh blood. Peripheral
blood smear showed a microcytic hypochromic picture with anisocytosis
and poikilocytosis. Liver function test (LFT) was abnormal with
unconjugated hyperbilirubinemia, transaminitis but a normal prothrombin
time and international normalized ratio (PT/INR), with the platelet
count always in the normal range. Her viral serology profile was send
and was found to be negative . She had a high lactate dehydrogenase
(LDH) value and a negative Direct-Coomb's test. Her lab reports are
mentioned in the table~1.

Table 1\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\textbf{Parameters} & \textbf{At the time of admission} & \textbf{At the
time of discharge} & \textbf{Normal reference used}\tabularnewline
\midrule
\endhead
Hemoglobin & 5.8 gm\% & 8.2 gm\% & 12.0-16.0 gm\%\tabularnewline
Total count & 11200/cubic mm & 10570/cubic mm & 4500-11,000/ cubic
mm\tabularnewline
Platelet count & 371000/cubic mm & 286000/cubic mm &
150,000-400,000/cubic mm\tabularnewline
Direct Coombs test & Negative & &\tabularnewline
PT/INR & 12sec/0.85 & 13 sec/1 & 11-15 sec\tabularnewline
Total bilirubin & 668 \selectlanguage{greek}µ\selectlanguage{english}Mol/L & 143 \selectlanguage{greek}µ\selectlanguage{english}Mol/L & 3-21 \selectlanguage{greek}µ\selectlanguage{english}Mol/L\tabularnewline
Direct bilirubin & 172 \selectlanguage{greek}µ\selectlanguage{english}Mol/L & 117 \selectlanguage{greek}µ\selectlanguage{english}Mol/L & 0-5 \selectlanguage{greek}µ\selectlanguage{english}Mol/L\tabularnewline
SGOT & 133 U/L & 203 U/L & 12-38 U/L\tabularnewline
ALP & 141 U/L & 80 U/L & 25-100 U/L\tabularnewline
SGPT & 55 U/L & 156 U/L & 10-40 U/L\tabularnewline
LDH & 2532 U/L & 230 U/L & 45-200 U/L\tabularnewline
Serum ceruloplasmin & 63 mg/dl & 76 mg/dl & 20-60 mg/dl\tabularnewline
24 hr urine copper & 298.8 mcg & ------ & \textless{}60
mcg\tabularnewline
USG abdomen and pelvis & Fetus of 28 weeks, cephalic EFW 1400 gm; AFI
5.3 cm Hepatomegaly; portal vein 9 mm & &\tabularnewline
Hepatitis A, B, C, ~and E IgM/IgG & Negative & &\tabularnewline
\bottomrule
\end{longtable}

The presence of Coomb's negative hemolytic anemia suggested a non-immune
etiology of hemolysis. Her glucose-6-phosphate dehydrogenase~(G6PD)
activity was normal. On suspicion of Wilson's Disease, we sent a 24-hour
urine collection for copper quantification, which came out to be 298
mcg/24 hr. However, her ceruloplasmin was 76 mg/dl (20-60 mg/dl). The
patient deferred the liver biopsy. The abdominal ultrasonography
revealed a fetus of 28 weeks gestation with normal heart rate and fetal
movements, hepatomegaly with perihepatic cuffing suggestive of acute
hepatitis. With strong suspicion of Wilson's disease, she was again sent
to a senior ophthalmologist for KF ring evaluation. She was then found
to have the KF ring on a slit-lamp examination.

Her treatment began with tab penicillamine 250 mg twice a day and tab
zinc 40 mg twice a day, where the gap of two hours between penicillamine
and zinc tablet administration was assured. She was also given a
pyridoxine tablet of 10 mg /day. She had gradual improvement in her
clinical symptoms of jaundice and anemia. Her hemoglobin level improved
to 8.2 g/dl, and her LFT and LDH were normalizing.~After two years of
follow-up, she does not have jaundice or anemia, and her lab parameters
are within the normal range with no hemolytic features. She is currently
under penicillamine 250 mg once a day and a copper restricted diet. She
had pre-term delivery of a 2.3 kg baby by cesarean section at 34 weeks
of gestation. Her baby weighs 12 kg at present. The 24-hour urine copper
analysis could not be sent because of financial reasons.~Neither the
genetic analysis could be done for the same reason.

\subsubsection*{Discussion}

{\label{discussion}}

Progressive hepatolenticular degeneration or Wilson's disease is a rare,
potentially treatable autosomal recessive disorder of the copper
transport caused by ATP7B gene mutation in the long arm of chromosome
13~{[}1{]}. WD's prevalence was thought to be 1 in 100,000 people.
However, with the advancement of studies, the estimated prevalence is
now considered 1 case per 30,000 live births~{[}1,2{]}. Although
virtually no data is available from Nepal but neighboring country India
sheds some light on WD . Taly et al. have presented a cohort study that
reported approximately 15-20 cases of WD are registered annually at one
of India's major neurological hospitals at NIMHAMS, Bangalore~{[}6{]}.

Defective ceruloplasmin synthesis, impaired copper excretion, and
accumulation of copper in the tissues, mostly in the liver and brain, as
a result of a mutation in the ATP7B gene, are the main hallmarks of this
disease that presents itself as a broad spectrum of clinical
manifestations.

Acute intravascular Coombs negative hemolytic anemia is a characteristic
feature of acute hepatic failure in WD. Oxidative injury, altered
erythrocyte metabolism, and severely compromised antioxidant status is
caused by the toxic effects of copper that is released from necrotic
hepatocytes, which in turn results in Wilsonian hemolysis~{[}7,8{]}. WD
has a myriad of clinical manifestations ranging from asymptomatic to
chronic liver diseases, neuropsychiatric diseases, acute liver failure,
hemolytic anemia, or combinations of these problems. It often poses as a
diagnostic challenge to the physicians. The finding of a KF rings is an
essential indicator of critical copper overload and is present in 95\%
of patients with neurological symptoms and 50-60\% of patients without
neurological symptoms of WD~{[}4{]}.

There is no single confirmatory test for WD; a score was developed at
the eighth International Conference of Wilson's Disease based on
clinical and laboratory abnormalities, which helps diagnose WD~{[}9{]}.

The presence of KF rings, low serum ceruloplasmin levels, and high urine
copper excretion is enough to make a diagnosis of Wilson's
Disease~{[}9{]}. WD is an easily overlooked rare clinical entity because
it resembles other common disorders like viral hepatitis. However, if
detected early, effective treatments are available to manage the disease
that may help prevent or reverse the many manifestations of Wilson's
disease.

The majority of patients with Wilson's disease are diagnosed between 5
and 35 years of age, the mean age being 13.2 years~{[}3{]}. Children are
more likely to present with hepatological symptoms considering the
neurological manifestations develop only after the slow accumulation of
copper in the brain~{[}10{]}. The mean age at presentation for patients
with neurologic symptoms ranges between 15-21 years. Our patient
presented with hepatological symptoms of jaundice and hepatomegaly,
mimicking viral hepatitis. No neurological symptoms were observed, but
the classical ophthalmic manifestation of WD: the KF ring was present at
the age of 19 during the third trimester of her pregnancy.

24-hour urine copper excretion \textgreater{}100 mcg holds an important
diagnostic aid and is also used for the therapeutic monitoring of
Wilson's disease. The patient had elevated 24-hour urine copper
excretion, which can be seen in various liver diseases, but it is most
often below 100 mcg/24 hrs~{[}11,12{]}.

A liver biopsy could not be done, which is essential for quantifying the
hepatic copper concentration. The common observation in the liver
function test of a Wilson disease patient, as seen in this case, is the
elevated serum aminotransferase, which is typically less than 2000 with
an AST/ALT ratio of \textgreater{}2, wherein this patient AST/ALT ratio
is \textgreater{} 2.2~{[}11{]}. The ALP level is usually normal or
subnormal with an ALP: total bilirubin ratio of \textless{}4 as seen in
this particular case~{[}13{]}.

Apart from the common liver diseases that present in pregnancy, such as
jaundice, hemolysis, elevated liver enzymes, and low platelets (HELLP)
syndrome, intrahepatic cholestasis, and viral hepatitis, Wilson's
disease is also a very real possibility that may present itself as
hemolytic anemia with normal platelet count in pregnancy, as seen in
this case.

WD and pregnancy have a complicated relationship; the outcome of
pregnancy with WD in the past has not been great. Untreated WD can lead
to significant morbidity and mortality. Excessive copper accumulation in
the liver and uterus leads to metabolic disturbance and recurrent
miscarriage.

The normal range of ceruloplasmin in pregnancy is 300~to 1200 mg/L,
while it is 250~to 600 mg/L in a non-pregnant adult~{[}14{]}. Despite
the less likelihood of KF rings in a hepatic presentation; the patient
was found to have them.

During pregnancy, ceruloplasmin levels are elevated. Because of the
fetus, the physiological copper demand is also increased. There might be
an improvement in the symptoms of WD, and patients may experience a
period of remission~{[}15{]}. However, in symptomatic and asymptomatic
patients alike, life-threatening complications such as preeclampsia,
placental abruption have been experienced during pregnancy regardless of
the medications~{[}16,17{]}. The exact mechanism is not known, but it is
believed that increased copper in the uterus prevents the successful
implantation of the fetus, similar to a copper-containing intrauterine
contraceptive device~{[}18{]}. The outcome of Wilson's disease in
pregnancy has improved in recent years with the therapeutic evolution
and better understanding of the disease in asymptomatic women~{[}18{]}.
Although a pre-term delivery, this case is one such example of a
successfully treated Wilson disease diagnosed during pregnancy.

Currently, the treatment of WD consists of lifetime therapy aimed at
primarily copper detoxification by the chelators and prevention of
copper accumulation in the body by zinc salts or chelators themselves.
The primarily used chelator is D-penicillamine, while Trientine is
considered to be the second-line agent. Research suggests that although
teratogenous in animals, D-penicillamine is safe in pregnancy, which is
given with zinc acetate/ zinc sulfate, pyridoxine, and a low copper diet
for the maintenance of pregnancy~{[}19,20{]}. We started the treatment
of the patient with D-penicillamine and zinc.~As shown in this case, the
correct diagnosis and appropriate management of WD can lead to a
favorable outcome even in pregnancy.

\subsubsection*{}

{\label{section}}

\subsubsection*{}

{\label{section-1}}

\subsubsection*{Conclusions}

{\label{conclusions}}

To sum up, WD is an inheritable metabolic liver disease associated with
the accumulation of copper in the human body.~Pregnancies in patients
with WD are considered high risk, not only because it poses an obvious
risk to the mother but also because the accumulating copper could affect
the unborn fetus. The proper treatment of the mother with Zinc and
Penicillamine is said to be relatively safer and has a lower risk of
congenital disability. We have tried to establish that successful
pregnancy while suffering from WD is possible through the data collected
from our case, although it does require continuous treatment and good
compliance.

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\par\null

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