A 9-week-old male (ex 34 weeks gestational age, corrected age 3 weeks) had been referred to our Emergency Department with suspected surgical abdomen. He presented a 3-day history of non-bilious, non-bloody vomiting and a 2-week-history of increasing abdominal distention and scrotal swelling. The patient was the second child of his parents who are from Kerala, India, and distantly related (3rd degree cousins). The couple's firstborn son is healthy.
Pregnancy was complicated by moderate oligohydramnios and decreased fetal movements which led to urgent C-section. Mother denied fever or rash during pregnancy, and her urinalysis was normal.
Birth weight was 1970 g (20th weight percentile). The weight of the placenta is not known. APGAR was 8 and 8 after 1 and 5 min, respectively. He received CPAP and then oxygen via nasal cannula for a total of 3 days. A post-natal brain ultrasound study was reportedly normal, TSH was 12 mU/L, and he was discharged home after 6 days. Immunizations were up-to-date, including PCV13.
At presentation, the infant was alert, irritable, pale and grunting. He was normocephalic without dysmorphic features. There was no rash, no jaundice, no petechiae or ecchymoses. He was tachycardic at 175 beats per minute and tachypneic. The remainder of the cardiovascular and pulmonary findings was unremarkable. The abdomen was distended, tense and shiny with large ascites and no palpably enlarged liver or spleen. Substantial scrotal edema was noted. Weight (with edema) was 3.5 kg (0.01%, z score -3.83), length 52.5 cm (0.00%, z score -4.31), and head circumference 35.5 cm (0.04%, z score -3.35).
At the time of admission, there was large proteinuria, hypoalbuminemia, and hypercholesterolemia, consistent with nephrotic syndrome. Nephrotic range proteinuria was defined as a spot urine protein-to-creatinine ratio of >0.23 g/mmol (corresponding to >2.0 g protein/g creatinine). For details and definitions, see Table 1). The hemoglobin (Hb) level dropped from 100 to 69 g/L over the first 10 days of admission, with inadequate reticulocyte response and normal serum ferritin and iron levels. Serum C3 and C4 concentrations, measured on day 11 of admission, were decreased. The concomitant direct agglutination (Coombs) test was negative. Secondary findings were hypogammaglobulinemia, hypothyroidism with elevated TSH and low free T4 levels, hypovitaminosis D, low-normal serum ionized calcium (1.17 mmol/L) and moderately elevated intact PTH. ALT and AST were normal. GGT and bilirubin concentrations peaked during the first few days after admission (see Table 1).
The ultrasound (US) scan showed enlarged kindeys with mildly increased cortical echogenicity. Liver and spleen were of normal size and echotexture. The brain US study was normal, except the presence of thalamostriate mineralizing vasculopathy.
Cardiac echography demonstrated a small perimembranous ventricular septal defect of 2-3 mm with left-to-right shunt and patent foramen ovale, none requiring specific interventions.
Infectious disease workup revealed anti-CMV IgM antibodies and CMV DNA (by PCR) in blood and urine. Maternal screening during pregnancy for toxoplasma (IgG and IgM), rubella (IgM), HIV 1 & 2 antibodies/P24 antigen, hepatitis B (HBsAg) and hepatitis C (antibodies), and syphilis was negative. Subsequent CMV testing showed high maternal serum concentrations of CMV IgG, but no anti-CMV IgM.
Treatment consisted of frequent albumin infusions, diuretics and ACE inhibition, with improvement of ascites and peripheral edema. He also received L-thyroxin, vitamin D and oral penicillin prophylaxis, low-dose acetyl salicylic acid, iron, and indomethacin. In addition, he was vaccinated against Streptococcus pneumoniae (PCV13, twice) and hepatitis B.
Valganciclovir treatment was initiated 9 days after presentation at a dose of 22 mg/kg/day. CMV DNA became undetectable in plasma and urine after 1 month of antiviral therapy, however proteinuria failed to improve (Table 1) strengthening the presumptive clinical diagnosis of a genetic form of congenital nephrotic syndrome.