Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunologic and metabolic abnormalities were studied in a five year old boy with 0.07 per cent of normal erythrocyte purine nucleoside phosphorylase activity. The clinical course is characterized by severe autoimmune hemolytic anemia, a transient neurologic disorder with tremor and ataxia, and minor infectious illnesses. There is severe lymphopenia with decreased absolute numbers of T and B lymphocytes. Mitogen-stimulated blastogenesis is reduced, but response to allogeneic lymphocytes is normal. A monoclonal IgG protein is present. There is hypouricemia, elevated plasma inosine level, hypouricosuria and an increase in the urinary concentration of inosine and guanosine. The pattern of heterozygote distribution in the patient's family is compatible with an autosomal recessive trait in which heterozygotes are identifiable. In addition, the unusual laboratory and clinical manifestations of this patient illustrate the heterogeneity of the clinical syndrome associated with purine nucleoside phosphorylase deficiency.
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PMID:Cellular immune deficiency with autoimmune hemolytic anemia in purine nucleoside phosphorylase deficiency. 11 49

We have studied patients with various immunodeficiencies for the occurrence of blood lymphocytes bearing six different surface markers: the affinity to sheep erythrocytes (Es) to identify T cells, the presence of surface-bound immunoglobulins (sIg) to distinguish B cells, the affinity to mouse erythrocytes (Em) as a second B cell marker, and the receptors for the Fc part of IgM (IgM-FcR), the Fc part of IgG (IgG-FcR) and for complement (CR). IgG-FcR bearing lymphocytes were present in normal proportions and the same was found for CR-positive lymphocytes. None of the patients with congenital agammaglobulinaemia had sIg-bearing or Em-binding B lymphocytes. Four patients with ataxia teleangiectasia had low B cells and 3 out of 4 also had low proportions of IgM-FcR-bearing (T) cells. A child with partial DiGeorge syndrome did not have a grossly abnormal marker pattern although there appeared to be a shift in the T/B cell ratio in favour of the B cells. In a patient with selective cellular immunodeficiency associated with a purine nucleoside phosphorylase deficiency, who was followed during reconstitution therapy with plasma and red cells, a positive change in the marker pattern was seen. Similar observations were made in a child with combined immunodeficiency during treatment. The findings are being discussed in the light of the current knowledge of the functions and ontogeny of lymphocyte subsets.
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PMID:Lymphocyte subpopulations in patients with various immunodeficiencies. 696 17

Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency and by complex neurologic symptomatology including ataxia, developmental delay, and spasticity. Herein we report severe marrow dysplasia in a patient with PNP deficiency. Drug-related marrow dysfunction was unlikely, and marrow virological studies were negative. A preleukemic myelodysplastic syndrome was also unlikely due to normal marrow CD34+ cells, colony growth in clonogenic assay of marrow mononuclear cells, apoptosis rate, and Fas expression on marrow nucleated cells, as well as morphologic improvement of the marrow dysplasia after normal red blood cell transfusion. The patient's marrow stroma showed hypersensitivity to irradiation and undetectable PNP enzyme activity similar to peripheral lymphocytes. This is the first report of PNP deficiency associated with increased lymphocyte and marrow stromal sensitivity to irradiation. We conclude that marrows from patients with PNP deficiency might have hypersensitivity to irradiation and can develop dysplastic morphology, caused either directly or indirectly by the inherited enzymatic defect.
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PMID:Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow morphology. 1471 4

Purine nucleoside phosphorylase (PNP) is an enzyme active in the purine salvage pathway. PNP deficiency caused by autosomal recessive mutations in the PNP gene leads to severe combined immunodeficiency (SCID) and in two thirds of cases also to neurological effects such as developmental delay, ataxia, and motor impairment.PNP deficiency has a poor outcome, and the only curative treatment is allogenic hematopoietic stem cell transplantation (HSCT). We present the first Swedish patient with PNP deficiency with novel mutations in the PNP gene and the immunological results of the HSCT and evaluate the impact of HSCT on the neurological symptoms. The patient presented early in life with neurological symptoms and suffered later from repeated serious respiratory tract infections. Biochemical tests showed severe reduction in PNP activity (1% residual activity). Genetic testing revealed two new mutations in the PNP gene: c.729C>G (p.Asn243Lys) and c.746A>C (p.Tyr249Cys). HSCT was performed with an unrelated donor, resulting in prompt and sustained engraftment and complete donor chimerism. There was no further aggravation of the patient's neurological symptoms at 21 months post HSCT, and appropriate developmental milestones were achieved. HSCT is curative for the immunological defect caused by PNP deficiency, and our case strengthens earlier reports that HSCT is effective as a treatment even for neurological symptoms in PNP deficiency.
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PMID:Novel Genetic Mutations in the First Swedish Patient with Purine Nucleoside Phosphorylase Deficiency and Clinical Outcome After Hematopoietic Stem Cell Transplantation with HLA-Matched Unrelated Donor. 2596 30