Case Studies
Autosomal Recessive DOPA-responsive Dystonia
The diagnosis of sepiapterin reductase deficiency in a patient at the age of 14 years was delayed by an earlier diagnosis of an initially unclassified form of methylmalonic aciduria at the age of 2. At that time the hypotonia and delayed development were not considered to be suggestive of a neurotransmitter defect. The clinically relevant diagnosis was only made following the onset of dystonia with diurnal variation, when the patient was a teenager. Variability in occurrence and severity of other symptoms of the condition, such as hypotonia, ataxia, tremors, spasticity, bulbar involvement, oculogyric crises, and cognitive impairment, is comparable with autosomal dominant GTPCH and tyrosine hydroxylase deficiency, which are both classified as forms of DOPA-responsive dystonia. Homozygous Mutation causing Parkinsonism
Hypotonia and Parkinsonism were present in two Turkish siblings, brother and sister. By using exome sequencing, which sequences a selective coding region of the genome, researchers have found a homozygous five-nucleotide deletion in the SPR gene which confirmed both siblings were homozygous. It is predicted that this mutation leads to premature translational termination. Translation is the biological process through which proteins are manufactured. The homozygous mutation of the SPR gene in these two siblings exhibiting early-onset Parkinsonism showcases that SPR gene mutations can vary in combinations of clinical symptoms and movement. These differences result in a wider spectrum for the disease phenotype and increases the genetic heterogeneity causing difficulties in diagnosing the disease.
The U.S. government (department of Health and Human Services) gave BioCryst Pharmaceuticals more than $77 million to finish the Phase III clinical development of peramivir. In 2009 the department of Health and Human Services had already given about $180 million to the program. Biocryst also donated 1200 courses of treatment to the US department of Health and Human Services. The Emergency Use Authorization expired on June 23, 2010. In 2011 a phase III trial found the median durations of influenza symptoms were the same with 1 intravenous injection of peramivir against 5 days of oral oseltamivir for people with seasonal influenza virus infection.In 2012 BioCryst reported that it should halt enrollment on its study for intravenous peramivir in potentially life-threatened people after an interim analysis led trial monitors to conclude that it would be futile to continue and the trial should be terminated. The difference between peramivir and control group (oral oseltamivir) for the primary endpoint, clinical or virologic, was small. In 2013 the Biomedical Advanced Research and Development Authority (BARDA/HHS) released new funding under the current $234.8 million contract to enable completion of a New Drug Application filing for intravenous (IV) peramivir.According to a research report published in June 2011, a new variant of swine flu had emerged in Asia with a genetic adaptation (a S247N neuraminidase mutation) giving some resistance to oseltamivir and zanamivir, but no significant reduction in sensitivity to peramivir. But a H274Y virus mutation showed resistance to oseltamivir and peramivir, but not to zanamivir, and only in N1 neuraminidases.