studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1049A
1724
Zinc monotherapy for young pediatric patients with presymptomatic
Wilson disease: a two-center experience in
Japan
Keisuke Eda 1 , Itaru Iwama 2 , Takahito Takeuchi 1 , Yugo Takaki 1 ,
Tatsuki Mizuochi 1 ; 1 Pediatrics, Kurume University School of Medicine,
Kurume, Japan; 2 Pediatrics, Okinawa Chubu Hospital,
Uruma, Japan
Purpose: We previously reported that a reasonable goal in
treating young pediatric patients with Wilson disease (WD)
using zinc to be maintaining 24-hour urinary copper excretion
between 1 and 3 μg/kg/day for the first 1-2 years (Mizuochi,
et al. JPGN 2011;53:365). Here, we aimed at evaluating
long-term efficacy and safety of zinc monotherapy for
young pediatric patients with WD and establishing appropriate
benchmarks of maintenance therapy. Methods: We performed
a retro- and prospective study to examine 7 girls (median age
5 years, range 4-8) who satisfied diagnostic criteria for WD
and were treated solely with zinc acetate prior to symptom
onset at Kurume University Hospital and Okinawa Chubu Hospital
in Japan. No additional WD sequelas, such as jaundice,
hepatomegaly, or neurologic abnormalities were noted. We
monitored serum AST and ALT, nonceruloplasmin serum copper,
and 24-hour urinary copper for 2-7 years after initiation
of zinc monotherapy. Additional monitorings included white
blood cell count, hemoglobin, platelet count, serum total bilirubin,
albumin, iron, amylase, lipase, and prothrombin time, as
well as 24-hour urinary zinc excretion. We performed abdominal
ultrasonograpy and evaluated clinical WD manifestations,
drug compliance, and adverse effects of zinc. The prescribed
dosage of zinc acetate for patients ≤ 5 years 25 mg twice
daily; for those children 6 years or older, the dose was 25 mg
3 times daily. We increased the dosage of zinc if the patients
had AST/ALT > 50 U/L, and decreased it if they had adverse
effects of zinc such as iron-deficiency anemia or pancytopenia.
Results: At the time of diagnosis, AST/ALT and 24-hour urinary
copper were 207±182/292±211 U/L and 143±68 μg/day
(7.2±3.5 μg/kg/day), respectively. All patients continued to
take zinc without any evidence of zinc toxicity. None of our
7 patients became clinically symptomatic. AST/ALT sharply
decreased to 35±7/37±16 U/L at 1 year after treatment and
was mostly maintained less than 50U/L for the remainder of
the study (AST/ALT: 35±9/42±29 and 33±9/41±17 U/L at
2 and 6 years after treatment, respectively). Twenty four-hour
urinary copper decreased to 54±18 μg/day (2.3±0.6 μg/
kg/day) at 1 year after treatment and was mostly maintained
between 1 and 3 μg/kg/day for the remainder of the study
(1.7±0.7 and 1.9±0.9 μg/kg/day at 2 and 6 years after treatment,
respectively). Conclusions: Long-term zinc monotherapy
for young pediatric patients with presymptomatic WD proved
highly effective and safe. A reasonable goal in treating young
children with WD using zinc appears to be maintaining both
AST/ALT under 50 U/L and 24-hour urinary copper excretion
between 1 and 3 μg/kg/day.
Disclosures:
The following authors have nothing to disclose: Keisuke Eda, Itaru Iwama, Takahito
Takeuchi, Yugo Takaki, Tatsuki Mizuochi
1725
Congenital Lactic acidemia (CLA), Amino acidemia (AA),
Urea cycle defects (UCD) and Organic acidemia (OA)
presenting with hepatic dysfunction in sick infants and
children: Diagnosis, Management and Outcome in a
Pediatric hepatology unit at a specialized liver centre in
India.
Seema Alam, Vikrant Sood, Bikrant B. Lal, Dinesh Rawat; Pediatric
Hepatology, ILBS, New Delhi, India
CLA, AA, UCD, OA are a group of MLDs which present with life
threatening illness and various grades of hepatic dysfunction.
Early recognition and management is of utmost importance in
countries with limited Newborn Screening Programme. Here
we present diagnosis, management and outcome children with
various causes of CLA, UCD and OA following an algorithmic
approach (Fig 1). Lactate and pyruvate ratio cam differentiate
between various congenital lactic academia. There were 7
cases of CLA including 3 cases of Fructose 1, 6 biphosphatemia,
1 case of respiratory chain defect (RCD) and one case of
(PEPCK, phosphoeno pyruvate carboxykinase). The three cases
of Fructose 1, 6 biphosphatemia were managed with fructose
free diet and recovered completely. The infants with RCD (management
with Carnitine, Coenzyme Q10, Riboflavine and low
carbohydrate diet) and PEPCK (supportive management) died.
A newborn presenting as neonatal liver failure and HCC was
diagnosed to be Tyrosinemia type 1 and the parents refused
the option of liver transplant and medical management. A 3
years old girl with UCD (Partial Ornithine transcarbamyolase
deficiency) presented as acute liver failure and completely
recovered with ammonia scavengers and awaiting liver transplant.
Another UCD presented with hepatic dysfunction at 2
months of age and died of encephalopathy. The only newborn
with hepatic dysfunction and Propionic academia improved
from the metabolic acidosis and ketosis with appropriate diet
and was sent home with the option of liver transplant in the
plan. A detailed protocol and algorithmic approach can help
in early diagnosis and management of these rare liver diseases
which in turn improves their outcome.
Figure 1. Protocol based approach to life threatnimg illness with
hepatic dysfunction.
Disclosures:
The following authors have nothing to disclose: Seema Alam, Vikrant Sood,
Bikrant B. Lal, Dinesh Rawat