Early effect of NTBC on renal tubular dysfunction in hereditary tyrosinemia type 1.

BACKGROUND: Hereditary tyrosinemia type 1 (HT1) is characterized by severe progressive liver disease and renal tubular dysfunction. NTBC therapy has revolutionized the management of HT1 but its effect on renal tubular function has so far been poorly investigated. The aim of this study was to describe the early effect of NTBC on renal tubular disease in patients with HT1. METHODS: Five HT1 patients (age between 5 and 53 months) with different types of presentation were evaluated before and during the first 2 weeks of therapy with NTBC in a retrospective case analysis for phosphate metabolism and renal tubular function. RESULTS: Before starting NTBC therapy, all children manifested signs of renal dysfunction which included hypophosphatemia, acidosis, reduced phosphate reabsorption, aminoaciduria, glycosuria (Fanconi syndrome), and variable degree of proteinuria. Some patients also presented increased urinary calcium/creatinine ratio and raised fractional excretion of sodium. Starting of NTBC therapy resulted in the rapid normalization of plasma phosphate within one week from its initiation in majority of patients and in all patients during the second week of therapy. TmP/GFR normalized in 48h, while the other markers of renal dysfunction showed an improving trend over 2 weeks. CONCLUSIONS: NTBC is an efficient treatment for renal tubular dysfunction in HT1, allowing the return to normal function within a few weeks. Its early effect on renal tubular cells appeared to be very rapid, particularly in normalizing plasma phosphate and TmP/GFR. In our series of patients, the TmP/GFR resulted as the most reliable index of tubular function.

MRI and 1H-MRS findings in early-onset cobalamin C/D defect.

OBJECT: Cobalamin C/D defect is an inborn error of cobalamin metabolism causing methylmalonic aciduria and homocystinuria. The early-onset form is characterized by severe neurological impairment. The aim of this study was to evaluate and monitor brain damage in early-onset cbl-C/D defect by conventional MRI and to assess the additional value of 1H-MRS. METHODS: We retrospectively examined serial MRI studies of 7 patients, performed on a 1.5 T system. Four patients had the first evaluation within the first 4 months of life and three later. The imaging protocol included spin-echo T1-weighted, T2-weighted, IR, and FLAIR. Five patients underwent 1H-MRS, using chemical shift imaging (CSI) in three patients and single voxel spectroscopy (SVS) in two. RESULTS: Three of the patients studied early showed tetraventricular hydrocephalus and diffuse swelling of supratentorial white matter with involvement of the "U" fibres. Two showed patchy cavitating lesions in the basal ganglia. White matter changes became evident at a later stage. In three cases 1H-MRS showed an abnormal peak of lactate in the basal ganglia or in the periventricular white matter. CONCLUSIONS: Our study shows severe heterogeneous brain MR abnormalities in cbl-C/D defect. We observed unusual basal ganglia lesions in 30 % of our cases and also found a high incidence of hydrocephalus and supratentorial white matter abnormalities.

Inborn errors of metabolism: an update on epidemiology and on neonatal-onset hyperammonemia.

Inborn errors of metabolism (IEM) are a highly heterogeneous group of genetic conditions and represent a relevant cause of morbidity and mortality in the pediatric population. IEM, which are individually rare but collectively numerous, are well-recognized entities of the generic class of "rare" diseases. Since the first descriptions by Garrod at the beginning of the 20th century, several hundred new disorders have been defined, as new biochemical and molecular diagnostic tools became available. The clinical pictures of single diseases are extremely diverse, ranging from acute life-threatening manifestations to chronic late-onset forms, with single or multiorgan involvement. Mental retardation and progressive neurological impairment often characterize the clinical course. One of the principles to prevent high morbidity and mortality rates is early recognition followed by prompt therapeutic intervention. Therefore, a small number of treatable IEM is subject to neonatal mass screening. More recently, an innovative technique, based on tandem mass spectrometry, has expanded the range of neonatal screening to several additional disorders. Owing to the extreme heterogeneity, as well as to the increasing number of new disorders, exhaustive and updated epidemiological data on the overall occurrence of IEM are lacking. A national retrospective study was conducted to define the epidemiological profile of IEM in Italy and to estimate the costs related to the disease burden. Other relevant issues of our investigations focused on creating protocols of treatment for neonatal IEM, and on the development of new methods for the biochemical diagnosis.

Successful pregnancy in a woman with mut- methylmalonic acidaemia.

We report on a favourable pregnancy in a woman affected by mut- methylmalonic acidaemia. Under vitamin B12 and carnitine therapy she remained symptom-free throughout pregnancy, labour, delivery and the postpartum period and gave birth to a term, healthy female newborn. At follow-up, the child shows normal somatic and neurocognitive development.