A patient with recurrent and severe CNS infections

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A patient with recurrent and severe CNS infections

• Maurício Domingues Ferreira, PhD
• University of São Paulo. Faculty of Medicine -
  Laboratory of Medical Investigation in
  Dermatology and Immunodeficiency (LIM-56)

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A patient with recurrent and severe CNS infections

• A 31 years-old male patient, African-Caucasian
  ethnical origin, born to a non consanguineous
  family by natural delivery without
  intercurrences, breast fed for 6 months with
  normal neuropsychomotor and pondero-statural
  development.
• He did not have important health problems up to
  25 years old, when he lost 10 Kg in a few months
  and had 3 pneumonias.
• Some months later he had symptoms of progressive
  headache, vomiting, fever, seizures and decrease
  of the consciousness level.

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A patient with recurrent and severe CNS infections

• A lumbar puncture, a Cranial and Spinal cord
  CT/MR scan and peritoneal biopsy were performed,
  leading to the diagnosis of Neurotuberculosis in
  the spinal cord and the brain associated with
  peritoneal tuberculosis.
• As sequelae he acquired spastic paralysis and
  hydrocephalus with chronic intracranial
  hypertension.
• He was submitted twice to ventricular-peritoneal
  shunting and treated with pyrazinamide,
  isoniazid, and rifampin. Later on, Amitryptilin,
  phenytoin and phenobarbital were introduced and
  he takes these drugs up to nowadays.

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A patient with recurrent and severe CNS infections

• He presented three central nervous system
  infections more between 2001-2004
• Cerebral Mucormycosis diagnosed by stereotaxic
  biopsy (2001).
• Cerebral Toxoplasmosis diagnosed by CT/MR scan
  and cerebrospinal fluid analysis (2002).
• Cerebral Nocardiosis diagnosed by stereotaxic
  biopsy (2004).
• He got important sequelae dementia, paraparesis
  and neurogenic bladder.

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A patient with recurrent and severe CNS infections
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A patient with recurrent and severe CNS infections
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A patient with recurrent and severe CNS infections

• Complete blood count normal
• Glucose 85 mg/dl
• Anti-HIV 1/2 negative
• IgA 960mg/dL (NR69-382)
• IgG 146mg/dL (NR952-1538 mg/dL)
• IgM 249 mg/dL (NR 73-171mg/dL)
• Kappa 90 mg/dL (NR 138-375 mg/dL)
• Lambda 86mg/dL (NR93-242 mg/dL)
• Normal and stable number of lymphocytes and their
  subsets (CD3, CD4, CD8, CD19, CD3-CD56,
  CD3CD56, CD4/CD45RA, CD4/CD45RO).
• His lymphoproliferative response to mitogens
  (PHA, OKT3 and PWM), as well as to Candida,
  Tetanus Toxoid, PPD, Cytomegalovirus, Varicella,
  and Toxoplasma antigens were absolutely normal.

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A patient with recurrent and severe CNS infections

• C3 151mg/dL (NR 90-180 mg/dL)
• C4 33mg/dL (NR10-40 mg/dL)
• CH50 and APH50 normal.
• Toxoplasmosis IgG positive IgM negative
• Varicella IgG positive IgM negative
• Epstein Barr virus IgG positive IgM negative
• Cytomegalovirus IgG positive IgM negative
• Anti-HBc IgG positive IgM positive
• Anti-HBe negative
• AgHBs positive
• Anti-HBs negative
• Hepatitis C serology negative

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A patient with recurrent and severe CNS infections

• Neutrophil chemotaxis with patients serum
• Patient 55,25mm Control 102,35mm
• (Normal range 91,48 - 137,22mm)
• Dihydrorhodamine (DHR) stimulated by PMA 36,55
  control 90,8 (Normal range 90 100)
• Glucose-6-phosphate dehydrogenase (G6PD) 1,0
  IU/g Hb/min 37oC (Reference value 12,1/-2,09)

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A patient with recurrent and severe CNS infections

• There are few reports demonstrating that G6PD
  deficiency can lead to recurrent bacterial and
  fungal infections similar to chronic
  granulomatous disease due to a disruption of the
  production of reactive oxygen species (ROS) used
  to kill ingested pathogens.
• G6PD is the rate-limiting enzyme of the pentose
  phosphate pathway. It catalyzes the
  dehydrogenation of the hydroxyl group located on
  carbon 1 of glucose 6-phosphate, converting it
  into a keto group, and in the process, NADPH is
  generated. NADPH is the substrate of NADPH
  oxidase present in phagocytes, which produces
  superoxide to kill infectant microorganisms. The
  reaction summary is as follows
• Glucose 6-phosphate 2 NADP H2O ribose
  5-phosphate 2 NADPH 2 H CO2
• CGD is caused by a defect in phagocytic NADPH
  oxidase, which is responsible for producing O2-.
  This superoxide anion is then converted to
  relatively bactericidal reactive oxidants, such
  as hydroxyl radical (OH-), hydrogen peroxide
  (H2O2), peroxynitrite anion (ONOO-), and
  oxyhalides (HOX-, in which the X moiety is most
  commonly chlorine). The superoxide anion is
  generated by transferring electrons from the
  reduced NADPH to molecular O2 in response to
  physiologic stimuli, such as phagocytosis.

G6PD
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