Dr Monica Thiyagarajan did her MS in Obstetrics and Gynaecology from JIPMER, Puducherry, MBBS from Government Dharmapuri Medical College, Tamil Nadu, and currently, pursuing her Mch in Gynaecological Oncology from Christian Medical College, Vellore.
Wilson’s disease (WD) is an autosomal recessive disorder due to the mutation in the ATP 7B gene. This gene is on chromosome 13 and codes for P-type ATPase which is responsible for transport of copper from intracellular chaperone proteins in hepatocytes into the secretory pathway. There is defective incorporation of copper into apo-ceruloplasmin for synthesis of functional ceruloplasmin as well as improper biliary excretion of copper, which leads to its accumulation in liver, brain and cornea [1]. The clinical presentation of WD varies widely. In an Indian cohort studied over three decades by Taly et al., 69.1% presented with neurological manifestations followed by hepatic, pre-symptomatic, hepato-neurological, psychiatric and Osseo-muscular in that order. Majority present between the age of 5 and 35 years [1]. The commonest association in women of reproductive age group is with infertility and recurrent abortions [2]. We present a case of a 30-year-old woman with rare presentation of neurological symptom in the postnatal period. The workup which led to the diagnosis of Wilson’s disease is detailed.
A 30-year-old woman, G3A2, was admitted at 39 weeks of gestation in active labor. She was booked at a private hospital outside and had an uncomplicated antenatal period. She delivered a live, male baby of 3.4 kg by outlet forceps. After 24 hours of delivery, fine tremors of both hands were noted during rest and exaggerated during posture. On general physical examination, the pulse rate was 86 beats per minute and blood pressure was 110/70 mm of Hg. There was no icterus or eye signs of hyperthyroidism. Abdominal examination revealed marked splenomegaly. Liver was not palpable. On examination for higher mental status, the patient was conscious, alert, oriented and no memory loss was noted. Cranial nerve examination was done, and all reflexes were found to be intact. On motor system examination, the patient had normal gait, power of 5/5 in all four limbs, normal muscle tone; fine tremors of both hands were noted during rest and exaggerated during posture, and there were no other abnormal movements such as chorea, athetosis, dystonia or dysarthria. Superficial, deep and cortical sensations were normal. Cerebellar function tests were normal. Parkinsonian features such as rigidity, bradykinesia, parkinsonian gait, postural instability and micrographia were absent.
Investigations
Her blood investigations showed normocytic normochromic anemia [Hb-9 g/dL] and thrombocytopenia [platelet count 45,000/μL]. Her thyroid function tests, liver function tests and renal function tests were within normal limits. Ultrasound abdomen showed altered echotexture of liver, suggestive of parenchymal liver disease, and splenomegaly with dilated portal and splenic veins (Fig. 1), suggestive of portal hypertension.
Diagnosis
Based on the symptoms, clinical examination, blood investigations and ultrasound findings, Wilson’s disease was suspected in our patient. A slit lamp examination was done which showed the presence of Kayser–Fleischer ring (Fig. 2) in both eyes. Biochemical tests revealed low serum ceruloplasmin [0.03 g/L], normal serum copper [95.40 μg/dL or 14.98 μmol/L] and normal 24-h urine copper [34.8 μg/24 h or 0.55 μmol/24 h]. Diagnosis of WD was confirmed as the patient presented with neurological symptom along with KF ring and low serum ceruloplasmin. Upper gastrointestinal (GI) endoscopy did not show any evidence of esophageal varices. MRI of brain showed mild atrophy of midbrain and pons.
Treatment
The patient was started on d-penicillamine tablet 500 mg twice daily. On follow-up, there was no worsening of tremors. Penicillamine can be given safely in lactating mothers as few studies suggest penicillamine was not detectable in breast milk but it reduced the copper and zinc secretion in breast milk, the effects of which are not known.
Wilson’s disease is an autosomal recessive disorder with a
similar prevalence worldwide of about 1 in 30,000 [1, 3].
There is no single diagnostic test for Wilson’s disease. A
scoring system for diagnosis based on clinical and laboratory
parameters was proposed at the eighth international conference
on Wilson’s disease, which might be of some help in
making a diagnosis [Table 1].Patients presenting with liver
disease with a decreased serum ceruloplasmin and detectable
Kayser–Fleischer rings have been generally regarded
as having classic WD.
Our patient had a score of 5 based on the scoring system
and was diagnosed to have Wilson’s disease. Liver biopsy
for liver copper measurement was not considered necessary
as she already was diagnosed based on the above parameters.
Mutation analysis by whole-gene sequencing is possible
and should be performed on individuals in whom the
diagnosis is difficult to establish by clinical and biochemical
testing, and for screening family members; but mutation
analysis could not be done for our patient or family members
as she was not affording for the investigation.
In women, WD is known to cause menstrual irregularities,
infertility and recurrent abortions due to deposition of
excess copper in the uterus [4]. Reports on pregnancies in
patients with prior diagnosis of WD suggest that, in treated women, pregnancy can have an uneventful course and a successful
outcome [4, 5], whereas in untreated patients, recurrent
abortions are common. Obstetric complications such as
preeclampsia and abruption have been reported in patients
with Wilson’s disease. The presence of portal hypertension
increases the risk of bleeding from esophageal varices,
which can occur in 50% of pregnant women with varices and
mortality rate in patients with esophageal bleed in 50% [5].
Although it is rare to have a successful outcome in pregnancies
with undiagnosed and untreated WD, there are two
case reports which have described WD detection in the
postpartum period with a successful outcome of pregnancy.
Aydagmus et al. reported a successful outcome in a pregnancy
terminated due to suspected hemolysis, elevated liver
enzymes and low platelet count (HELLP) syndrome due to
preeclampsia with elevated liver enzymes, thrombocytopenia
and hemolysis. These features could have been due to
WD per se and were interpreted as HELLP syndrome; she
was evaluated for WD when she had persistently elevated
liver enzymes, bilirubin, INR, with bleeding manifestations
[6]. Similarly, in another case report, two cases have been
described who presented as HELLP syndrome and had successful
pregnancy outcomes but on further workup diagnosed
as WD. Our patient who also had a successful pregnancy
outcome had manifested in the immediate postnatal
period with neurological symptoms and was diagnosed by
that which has not been reported yet. As there are over 500
mutations causing WD, variable penetrance of mutation is
evident by the decreased number of cases who present with
clinical manifestation [2].
It is possible that high estrogen of pregnancy may delay
the hepatic failure as suggested by Kasai and colleagues
through studies done on animal model and as was seen in the
case by Shimono et al. where a previously diagnosed case of
WD on d-penicillamine treatment for 12 years had discontinued
treatment during her antenatal period and had an uneventful
course, but she developed hemolytic crises during
the immediate postnatal period from which she recovered
with supportive treatment and restarting d-penicillamine
but ultimately succumbed to a second hemolytic crises and
fulminant liver failure on postnatal day 50.
It can be extrapolated that withdrawal of high estrogen
and progesterone after pregnancy in puerperium may precipitate
presentation of Wilson’s disease symptoms in undiagnosed
patients.
In women most of them present before pregnancy with
classical symptoms of WD or with infertility and recurrent
abortions, there are rare cases like ours which are diagnosed
postnatally after an uneventful pregnancy. In young women
presenting with new onset neurological symptom like tremors
associated with splenomegaly, the workup for diagnosing
Wilson’s disease should also form priority as the progress of disease and target organ affection can be controlled by
appropriate treatment.
Acknowledgement We would like to thank the institute for their
support.
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical Statement All procedures performed in studies involving
human participants were in accordance with the ethical standards of
the institutional ethics committee and with the 1964 Helsinki declaration
and its later amendments or comparable ethical standards.
Human and Animal Rights This article does not contain any studies
with animals performed by any of the authors.
Informed Consent Informed written consent has been obtained from
the patient for the publication of the case report and images.
