Sex: F
Vaccine: HIBV, MMR, PPV, TTOX, VARCEL
Symptoms: Blood immunoglobulin G normal, Blood immunoglobulin M decreased, Full blood count normal, Immunoglobulin therapy, Laboratory test normal
Clinical narrative: Recurrent Pneumonia; Therapeutic response decreased; This case was reported in a literature article and described the occurrence of pneumonia recurrent in a 4-year-old female patient who received Hib UNK (Hib vaccine) for prophylaxis.   Co-suspect products included VZV VACCINE (batch number UNK, expiry date unknown) for prophylaxis, TETANUS VACCINE (batch number UNK, expiry date unknown) for prophylaxis, MEASLES MUMPS RUBELLA (batch number UNK, expiry date unknown) for prophylaxis and PNEUMOCOCCAL VACCINE POLYSACCHARIDE 23 VALENT (PNEUMOVAX) (batch number UNK, expiry date unknown) for prophylaxis.   The patient's past medical history included sickness, pneumonia (3 episode), fever (104 F requiring emergency department treatment) and vsd (since birth). Concurrent medical conditions included optic atrophy (bilateral), common variable immunodeficiency, gene mutation (neuroblastoma amplified sequence), short stature, liver failure (Infantile Liver Failure Syndrome), neutrophil pelger-huet anomaly present, hypogammaglobulinemia, skeletal dysplasia and retinal dystrophy.   On an unknown date, the patient received Hib vaccine, VZV VACCINE, TETANUS VACCINE, MEASLES MUMPS RUBELLA and PNEUMOVAX. On an unknown date, unknown after receiving Hib vaccine, the patient experienced pneumonia recurrent (serious criteria GSK medically significant) and therapeutic response decreased. The patient was treated with immunoglobulin. On an unknown date, the outcome of the pneumonia recurrent and therapeutic response decreased were unknown.   It was unknown if the reporter considered the pneumonia recurrent and therapeutic response decreased to be related to Hib vaccine.  Additional details were provided as follows: This case was reported in a literature article and described the occurrence of recurrent pneumonia and decreased therapeutic response in a 4-year-old female patient, who was vaccinated unspecified Haemophilus influenzae type b (Hib), unspecified measles, mumps and rubella vaccine (MMR) unspecified varicella zoster vaccine (VZV) and pneumovax vaccines (manufacturer unknown) for prophylaxis.   The patient born at 33 weeks gestational age. The patient was always S61and sicker than her friends. Prior 8 months, the patient had 3 episodes of pneumonia with fever to 104 F requiring emergency department treatment. Two of these were associated with RSV and metapneumovirus, respectively. The patient had a small VSD noted since birth, and bilateral optic atrophy identified during routine ophthalmology follow-up for prematurity.  The patient had concurrent condition of common variable immunodeficiency (CVID). No information on patient's family history or concomitant were provided.  On unspecified date, the patient had received Haemophilus influenzae type b (Hib), measles, mumps and rubella vaccine (MMR) varicella zoster vaccine (VZV) and pneumovax vaccines (administration route, site and batch number were not reported). Age at vaccination was not reported, but it could be 4 year old or less than 4 year old at the time of vaccination.  On unspecified date, unknown period after vaccination, the patient's parents sought a second opinion where the patient had an laboratory evaluation and which confirmed low levels of IgG (326 mg/dL) IgA (7) and IgM (6), and poor antibody responses to tetanus, Hib, MMR and VZV antigens. The patient's response to Pneumovax was marginal (+12 of 23 serotypes tested) and transient (#2 of 23 after 4 months). CBC including smear and chemistry panel were normal. Results of routine lymphocyte subset analysis were normal except for relatively low NK cells. On examination, patient appeared well. The patient height and weight were at the 20th percentiles. There was no evidence of active infection, hepatosplenomegaly, lymphadenopathy or skin rash. Ig replacement was initiated and continues as weekly infusions of SCIG, maintaining IgG levels over 1000 mg/dL. At 4.5 years, the patient was hospitalized for pneumonia, and transiently elevated transaminases (AST 117 U/L, ALT 552) were noted for the first and only time. The patient has not exhibited these findings (such as: Exome sequencing revealed okay heterozygous, likely pathogenic, variants limited to the C-terminal domain of the NBAS gene. The product of this gene was a component of the syntaxin 18 complex that was implicated in Golgi to ER retrograde transport. Mutations in NBAS are associated with Infantile Liver Failure Syndrome 2 (ILFS2, OMIM#616483) and Short Stature, Optic Atrophy and Pelger Huet Anomaly in neutrophils (SOPH syndrome). Hyopgammaglobulinemia and low NK cell numbers have been reported in affected patients, and NBAS deficiency was listed in the IUIS 2017 PID Committee report. Clinical features reported in NBAS deficiency include familial consanguinity, fever-related recurrent liver crises, short stature (less than 3 perecnt), skeletal dysplasia, cervical instability (small C1-C2) and retinal dystrophy). Our patient's NBAS variants are being studied for functional validity. A skin biopsy was performed and fibroblasts cultured for analysis. In contrast to our patient, by using Exome sequencing  revealed that variants both in the C-terminal domain, most reported cases have at least 1 mutation affecting domains further toward the N-terminus in our patient. Patient's fibroblasts do not show a clear reduction in NBAS protein, and protein interaction partners were not diminished.  The outcome was not provided.  The author did not commented on the relationship between the events decreased therapeutic response and recurrent pneumonia and haemophilus influenzae type b (Hib).