Case report:
A previously healthy 13-year-old Japanese boy was admitted to our
hospital with a 1-month history of fatigue, poor complexion, and
purpura. He had no history of congenital anomalies, prior association
with hepatitis, radiation exposure, or ingestion of drugs that might be
associated with AA. At admission to our hospital, his vital signs were
normal, and there was no clinical evidence of hepatomegaly or
splenomegaly. Heart sounds and lungs were normal. Laboratory data on
admission were as follows: red blood cell count,
1.43×1012 /L; white blood cell count,
2.38×109 /L with 14% neutrophils, 80% lymphocytes,
2% monocytes, 4% eosinophils and no myeloblasts; hemoglobin level, 5.1
g/dL; platelet count, 0.9×109 /L; and reticulocyte
count, 25.7×109 /L. A bone marrow biopsy showed
markedly hypocellular bone marrow without apparent dysplasia or blasts,
the karyotype was 46,XY [20], and 1.0% of marrow cells had monosomy
7 as determined by 7q31 interphase fluorescence in situhybridization (FISH) analysis. We diagnosed idiopathic AA after
excluding congenital AA based on a normal chromosomal breakage test and
no shortening of the telomere length. IST was started with rabbit
anti-thymocyte globulin (2.5 mg/kg, 110 mg/day, days 1 to 5),
cyclosporine (CsA; 5 mg/kg, 220 mg/day), methylprednisolone (2 mg/kg, 88
mg/day, days 1 to 7), and prednisolone (45 mg/day, days 8 to 14; 30
mg/day, days 15 to 19; 20 mg/day, days 20 to 24; and 10 mg/day, days 25
to 29). Transfusions were given as needed for anemia and
thrombocytopenia during IST. Recovery of hematopoiesis was gradually
observed, and transfusions became unnecessary from 54 days after IST. A
bone marrow biopsy at 4 months after the start of IST showed
normocellular bone marrow without apparent dysplasia or blasts, but
14.0% of the marrow cells had monosomy 7 as determined by FISH
analysis. The proportion of cells with monosomy 7 fluctuated over the
course of regular bone marrow biopsies, but the dosage of CsA was
gradually decreased without any additional treatment, because no
dysplasia and blasts were seen. However, about 3 years after the
diagnosis of AA, the patient was readmitted to our hospital due to a
sudden weight gain of 10 kg and anasarca.
At the time of NS onset at readmission, a physical examination showed
the following: body height, 169 cm; body weight, 65.9 kg; body
temperature 36.4°C; respiratory rate, 12 breaths/min; blood pressure,
115/61 mmHg; and anasarca edema, including on the eyelids, face, and
pretibial regions. A blood test at the same time showed the following:
total protein, 4.2 g/dL; albumin, 2.1 g/dL; lactate dehydrogenase, 237
U/L; and total cholesterol, 361 mg/dL. Urinary examinations showed the
following: urinary protein, 4+; occult blood in urine, 3+; urine
density, 1.015; and urinary protein, 8.32g/day, and urinary
protein-to-creatinine ratio, 7.09 g/g creatinine, by 24-h urine
collection. Pathological examination of a renal biopsy sample revealed
minor glomerular abnormalities (WHO 1995) without mesangial cell
proliferation, segmental glomerulosclerosis, or crescentic formation.
Based on the above results, we diagnosed minimal change NS (Figure 1).
The patient was started on corticosteroid therapy with 60 mg/day of
prednisolone in addition to the previously administered CsA. At 17 days
after the start of treatment, he achieved a complete response with a
urinary protein level of 0.11g/day and urinary protein-to-creatinine
ratio of 0.1 g/g creatinine by 24-h urine collection, and a serum
albumin level of 2.5 mg/dL. He was tapered off prednisolone 1 week
later, and was discharged 21 days after the start of treatment. The
proportion of bone marrow cells with monosomy 7 by FISH analysis was the
highest at 81% after the onset of NS. Figure 2 shows the course of the
case from the onset of AA, including the proportions of cells with
monosomy 7. We performed genetic testing, because the combination of
both diseases is rare but this case did not have any mutations in
germline SAMD9/9L mutation (SAMD9/9Lmut )
or somatic GATA2 mutation (GATA2mut ). At
this time, the genetic factors that lead to the development of both
diseases remain unknown.