Tyrosinemia type I (hepatorenal tyrosinemia, HT-1) is an autosomal recessive condition resulting in hepatic failure with comorbidities involving the renal and neurologic systems and long term risks ...for hepatocellular carcinoma. An effective medical treatment with 2-2-nitro-4-trifluoromethylbenzoyl-1,3-cyclohexanedione (NTBC) exists but requires early identification of affected children for optimal long-term results. Newborn screening (NBS) utilizing blood succinylacetone as the NBS marker is superior to observing tyrosine levels as a way of identifying neonates with HT-1. If identified early and treated appropriately, the majority of affected infants can remain asymptomatic. A clinical management scheme is needed for infants with HT-1 identified by NBS or clinical symptoms. To this end, a group of 11 clinical practitioners, including eight biochemical genetics physicians, two metabolic dietitian nutritionists, and a clinical psychologist, from the United States and Canada, with experience in providing care for patients with HT-1, initiated an evidence- and consensus-based process to establish uniform recommendations for identification and treatment of HT-1. Recommendations were developed from a literature review, practitioner management survey, and nominal group process involving two face-to-face meetings. There was strong consensus in favor of NBS for HT-1, using blood succinylacetone as a marker, followed by diagnostic confirmation and early treatment with NTBC and diet. Consensus recommendations for both immediate and long-term clinical follow-up of positive diagnoses via both newborn screening and clinical symptomatic presentation are provided.
Metabolic strokes are a notable feature associated with acute catabolic crises in patients with propionic acidemia. Despite their importance, these events are not well characterized. Here, we present ...the clinical history of a patient with propionic acidemia who developed 5 episodes of acute hemiparesis between 3 and 11 years of age. The clinical finding of hemiparesis associated with 4 of these 5 events were shorted lived (2-5 days). Neuroimaging showed signal changes in the basal ganglia manifesting many years following the initial episode. Two of the episodes were accompanied by definite seizures. Based on these factors, the hemiparetic events were most consistent with metabolic strokes, though what is distinctive is that most of the events occurred without evidence of metabolic decompensation; brain magnetic resonance imaging findings were not suggestive in the acute setting. We present a framework for evaluating suspected metabolic stroke in propionic acidemia, in light of the sometimes perplexing clinical heterogeneity underlining these events.
The rat hepatoma cell line H4IIEC3 has demonstrated a response to both insulin and glucocorticoids in its accumulation of BCKAD subunit RNAs. It is amenable to BCKAD promoter minigene transfection ...analyses, demonstrating positive (glucocorticoids) and negative (insulin) regulatory effects. These cells can therefore be used as a model to identify cis-acting sites responsible for regulation of BCKAD subunit promoter activity.
The presence of a spreading petechial rash in an acutely ill child with fever raises concern for sepsis, especially for meningococcemia. Two cases of febrile petechial rash pattern are discussed.
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