Severe Hemolytic Anemia and Metabolic Acidosis at Birth with Glutathione Synthetase Deficiency and Progressive Neurological Symptoms on Follow-Up.

BACKGROUND Glutathione synthetase deficiency (GSD) is a rare autosomal recessive disorder caused by glutathione synthetase (GSS) gene variants that occur in 1 in 1 million individuals. The severe form of GSD is characterized by hemolytic anemia, metabolic acidosis with 5-oxoprolinuria, progressive neurological symptoms, and recurrent bacterial infections. This case report presents a male Japanese infant with severe hemolytic anemia and metabolic acidosis at birth caused by GSD, who developed progressive neurological symptoms on follow-up. CASE REPORT A Japanese male term infant developed severe hemolytic anemia and metabolic acidosis in the early neonatal period. We suspected GSD based on his symptoms and a high 5-oxoproline urine concentration. We began correcting his metabolic acidosis and administering vitamins C and E supplements. The patient required blood transfusion twice during the acute phase for hemolytic anemia. After age 1 month, he maintained good control of metabolic acidosis and hemolytic anemia. A definitive diagnosis of GSD was made based on high concentrations of 5-oxoproline in urine, low concentrations of glutathione and GSS activity in erythrocytes, and genetic testing. Several episodes of febrile convulsions were started at age 11 months, but none occurred after 2 years. At the last follow-up at age 25 months, metabolic acidosis and hemolytic anemia were well controlled, but he had mild neurodevelopmental delay. CONCLUSIONS This case report shows that GSD can present with severe hemolytic anemia and metabolic acidosis at birth, and manifest with subsequent neurological impairment despite early diagnosis and treatment. Therefore, a careful long-term follow-up that includes neurological evaluation is essential for patients with GSD.

Transcutaneous bilirubin measurement during phototherapy in term neonates.

BACKGROUND: We tested whether direct transcutaneous bilirubin (TcB) measurement from an area unexposed to phototherapy is reliable for estimation of total serum bilirubin (TSB) in neonates during phototherapy and whether it contributes to reduction in TSB blood sampling in phototherapy decision making. METHODS: This was a retrospective observational study of term neonates who received phototherapy in the mother's room. TSB and TcB from the neonate's sternum were measured before and during phototherapy and compared using linear regression analysis and Bland-Altman plot, respectively. Various cut-offs of TcB for estimating TSB during phototherapy at >72 h after birth were analyzed. RESULTS: There were moderate correlations between TSB and TcB before (r = 0.56) and during (r = 0.47) phototherapy in 125 neonates. The mean difference (TSB-TcB) before and during phototherapy was 1.2 ± 1.7 mg/dL and 1.0 ± 1.7 mg/dL, respectively. The 95% limits of agreement for the difference before and during phototherapy ranged from -2.1 to 4.5 and from -2.3 to 4.3 mg/dL, respectively. For TSB ≤18 mg/dL during phototherapy, a TcB cut-off of 14 mg/dL had a specificity of 1.0; with this method, 43% of the TSB measurements could have been avoided. CONCLUSIONS: Direct measurement of TcB during phototherapy using a bed-type device is a reliable method to estimate TSB in term neonates and would contribute to a reduction in blood sampling. It cannot, however, be used as a substitute for TSB measurement.

Screening for Hyperbilirubinemia in Japanese Very Low Birthweight Infants Using Transcutaneous Bilirubinometry.

OBJECTIVES: To assess the accuracy of transcutaneous bilirubin (TcB) measurements at 5 different body sites in Japanese very low birthweight (VLBW) infants and to determine a cut-off value of TcB to detect total serum/plasma bilirubin (TB) levels ≥10 mg/dL (171 µM). STUDY DESIGN: In a prospective multicenter study, 85 Japanese VLBW infants were enrolled from 5 neonatal intensive care units during the study period. A total of 383 blood samples from infants not receiving phototherapy or ≥24 hours postphototherapy were analyzed. TcB was measured at the forehead, sternum, upper back, lower abdomen, and waist within 1 hour of blood collection. Linear regression analysis and Bland-Altman plots were used to compare TcB values at each site with TB levels. The TcB cut-off value for detecting TB ≥10 mg/dL was determined by receiver operating characteristics curve analysis. RESULTS: TcB significantly correlated with TB, but the coefficient of determination varied among the sites (forehead: 0.5294, sternum: 0.6488, upper back: 0.6321, lower abdomen: 0.5430, waist: 0.7396). At a TcB value ≥8, the sensitivity was 100% at the sternum and upper back, 85% at the waist, 84% at the forehead, and 64% at the lower abdomen to detect TB ≥10 mg/dL. CONCLUSIONS: In Japanese VLBW infants, the accuracy of TcB measurements varies according to body site. TcB ≥8 on the sternum or upper back is more reliable than that on the forehead, lower abdomen, or waist to detect TB levels ≥10 mg/dL.

High-dose calcium reduces early-onset hyperkalemia in extremely preterm neonates.

BACKGROUND: Early-onset hyperkalemia often occurs in extremely preterm infants during a few days after birth. While there are several treatments for hyperkalemia, calcium infusion to reduce plasma potassium concentrations remains controversial. The purpose of this study is to investigate whether a high dosage of calcium reduces early-onset hyperkalemia. METHODS: Extremely low-birthweight neonates born at 22-25 weeks' gestation were enrolled. We analyzed data using multivariate regression analysis and performed a retrospective cohort study with patients divided into two groups according to the dosage of calcium in their initial infusion. RESULTS: A total of 103 patients were eligible. Early-onset hyperkalemia was observed in 27 patients. The dosage of calcium gluconate during 24 h after birth was the only independent factor affecting early-onset hyperkalemia. The maximum plasma potassium concentration during 72 h after birth was negatively correlated with the dosage of calcium. High-dose calcium reduced occurrences of hyperkalemia and hypoglycemia caused by insulin infusion given for treatment of hyperkalemia, without increasing the risk of any other complications. CONCLUSIONS: Infusion of calcium gluconate may reduce early-onset hyperkalemia in a dose-dependent manner.

The significance of measurement of serum unbound bilirubin concentrations in high-risk infants.

BACKGROUND: In the management of neonatal hyperbilirubinemia, total bilirubin (TB) concentration is not specific enough to predict the brain damage caused by bilirubin toxicity. Unbound bilirubin (UB) easily passes the blood-brain barrier and causes neurotoxicity. We aimed to evaluate whether serum UB concentration would be a useful predictor of bilirubin encephalopathy in high-risk infants. METHODS: We measured the serum TB and UB concentrations of 388 newborn infants treated with phototherapy or exchange transfusion for their hyperbilirubinemia at Takatsuki General Hospital between January 2002 and October 2003. Peak serum TB and UB levels and UB/TB ratios were studied on each birthweight group: below 1500 g (very low birthweight), 1500 g-2499 g (low birthweight), above 2500 g (normal birthweight); and several clinical factors influencing hyperbilirubinemia were also studied. RESULTS: Peak serum TB and UB levels increased with increasing birthweight, while UB/TB ratios decreased. The very low birthweight group showed higher UB levels and UB/TB ratios despite lower TB levels in intraventricular hemorrhage or severe infection compared to those in the others. The low birthweight and normal birthweight groups showed higher TB and UB levels in cases of hemolytic disease of the newborn compared to non-hemolytic disease of the newborn cases. Eight of 44 cases showed high UB levels accompanied by abnormal auditory brainstem responses, one of whom subsequently developed ataxic cerebral palsy with hearing loss, whereas the other seven showed transient abnormalities of auditory brainstem responses by the treatment of exchange transfusion or phototherapy. CONCLUSION: The UB measurement was considered to be significant for the assessment of the risk of bilirubin neurotoxicity and the appropriate intervention for hyperbilirubinemia in high-risk infants.