Diffusion Tensor Imaging of Microstructural Changes in the Gray and White Matter in Patients With Crigler-Najjar Syndrome Type I.

PURPOSE: This study aimed to evaluate the role of diffusion tensor imaging of microstructural changes in gray and white matter in Crigler-Najjar syndrome type I. PATIENT AND METHODS: A prospective study was conducted on 10 patients with Crigler-Najjar syndrome type I and 10 age- and sex-matched children who underwent diffusion tensor imaging of the brain. Mean diffusivity (MD) and fractional anisotropy (FA) of gray and white matter were measured. RESULTS: There was a significantly higher MD of the gray matter regions including the globus pallidus, thalamus, caudate head, substantia nigra, and dentate nucleus in patients versus controls (P = 0.007, 0.001, 0.014, 0.003, and 0.002), respectively. The areas under the curve (AUC) of MD of the globus pallidus and thalamus used to differentiate patients from controls were 0.93 and 0.925, respectively. There was a significant difference in MD of the frontal white matter and posterior limb of the internal capsule in patients versus controls (P = 0.001 and 0.02), respectively. The AUCs of MD of these regions used to differentiate patients from controls were 0.82 and 0.8. There was a significant difference in FA of the frontal white matter and posterior limb of the internal capsule in patients versus controls (P = 0.006 and 0.006), respectively. The AUCs of FA of these regions were 0.83 and 0.85, respectively. The MD of the globus pallidus correlated with serum bilirubin (r = 0.87 and P = 0.001). CONCLUSION: Diffusion tensor imaging can detect microstructural changes of deep gray matter and some regions of white matter in Crigler-Najjar syndrome type I.

Ultrasound-guided in Utero Transplantation of Placental Stem Cells into the Liver of Crigler-Najjar Syndrome Model Rat.

BACKGROUND: Advances in prenatal screening and early diagnosis of genetic disease will potentially allow for preemptive treatment of anticipated postnatal disease by in utero cell transplantation (IUCT). This strategy carries potential benefits over postnatal treatment, which might allow for improved engraftment and function of the transplanted cells. Congenital metabolic disorders may be an ideal target for this type of therapy, as in most cases, they require replacement of a single deficient hepatic enzyme, and multiple small-animal models exist for preclinical testing. METHODS: The Gunn rat, a Crigler-Najjar syndrome model animal lacking UDP-glucuronosyltransferase (UGT1A1), was used as recipient. Human amniotic epithelial cells (hAECs), which possess hepatic differentiation potential, were transplanted into the midgestation fetal Gunn rat liver via ultrasound-guided IUCT. The impact of IUCT on live birth and postnatal survival was evaluated. Human cell engraftment was immunohistochemically analyzed on postnatal day 21. RESULTS: Ultrasound-guided IUCT was conducted in rat fetuses on embryonic day 16. Following IUCT, the antihuman mitochondria-positive cells were detected in the liver of recipient rats at postnatal day 21. CONCLUSIONS: Here, we have introduced ultrasound-guided IUCT of hAEC using a small-animal model of a congenital metabolic disorder without immunosuppression. The immunological advantage of IUCT was demonstrated with xenogeneic IUCT. This procedure is suitable to conduct preclinical studies for exploring the feasibility and efficacy of ultrasound-guided transuterine cell injection using rodent disease models.

Hepatic uptake of technetium-99m diisopropyl iminodiacetic acid (DISIDA) is not impaired by very high serum bilirubin levels.

The hepatic clearance of Tc-99m labeled iminodiacetic acid (IDA) compounds is believed to be impaired in patients with severe hyperbilirubinemia. Competitive inhibition of hepatocyte uptake of IDA by bilirubin has been demonstrated in vitro, but not by clinical scintigraphy. We present a patient with Crigler-Najjar syndrome without evidence of hepatobiliary damage, who demonstrated normal uptake and excretion of Tc-99m DISIDA despite a serum indirect bilirubin level in excess of 30 mg/dl. It is therefore suggested that a markedly elevated serum bilirubin level per se does not inhibit hepatic uptake of Tc-IDA and does not preclude clinically useful scintigraphic examination.