A Study of Vitamin B12 Status in Children With Infantile Tremor Syndrome and Pre Infantile Tremor Syndrome
Condition: Infant Nutrition Disorder
MeSH terms: Tremor; Nutrition Disorders; Infant Nutrition Disorders
Study type: Observational

Summary: 
      PRIMARY OBJECTIVES

      • To describe the vitamin B12 status in children with infantile tremor syndrome(ITS) and Pre
      ITS

      SECONDARY OBJECTIVES

        -  To study the vitamin B12 status in mothers of children with infantile tremor syndrome
           (ITS) and Pre ITS

        -  To study the blood levels of folate in children with infantile tremor syndrome (includes
           Pre ITS) and their mothers.
    

Detailed description: 
      Materials and methods

      STUDY SETTING: Hospital based study (Advanced Pediatrics Centre, PGIMER) STUDY PERIOD: July
      2015 to December 2016 STUDY DESIGN: Cross sectional, Observational Enrolment criteria
      Inclusion criteria (cases)

        1. Either sex, age less than 3 years

        2. Clinical diagnosis of Infantile Tremor Syndrome as evidenced by the following features:

      [Developmental delay or regression WITH history of exclusive or predominant breast feeding
      WITH two or more of the following; skin pigmentation, hair depigmentation, tremors] ITS:1 and
      2 plus tremors PreITS:1 and 2 without tremors Exclusion criteria (cases)

        1. Parents refusing consent

        2. Later confirmation of an alternative diagnosis

        3. Patient has received oral or injectable Vitamin B12 in the past 6 months Controls (C)-
           Normally developing children

             -  Inclusion criteria Developmentally normal child not suffering from any acute or
                chronic neurological illness

             -  Exclusion criteria

      1.Parent/individual refusing consent 2.Patient has received oral or injectable Vitamin B12 in
      the past 6 months

      PLAN OF THE STUDY All consecutive patients who present in Pediatric Emergency and OPD in
      Advanced pediatric Centre with suspected Infantile tremor syndrome will be screened for
      inclusion in the study. Those found eligible would be included after an informed consent.
      Baseline clinical and demographic profile will be recorded on a proforma..The study aims at
      assessment of vitamin B12 status in children with ITS. The various manifestations of the
      syndrome, the presentations, the clinical picture, the development profile, various
      haematological and biochemical markers would be studied in a detailed manner and recorded on
      a proforma (annexure).

      The first section of the proforma is targeted at the clinical picture of the disease. The
      presenting features will be recorded. The presenting complaints which can be anything ranging
      from an episode of upper respiratory tract infection to an apparently healthy child
      presenting with delayed milestones. A brief history of the development milestones achieved
      under gross motor, fine motor, language and social milestones is important and form a basis
      for screening the developmentally delayed children .A feeding history will be taken and is
      important as this disease is more frequently seen in children who are
      exclusively/predominantly breastfed. A detailed examination of the child would be done and
      the findings recorded. Skin and hair changes are very classical of this disease and hence
      will be to be studied and recorded in detail. A neurological examination will be done to
      study the neurological status of the children and presence of any extrapyramidal symptoms.
      Hematological indices will be recorded. Plasma Vitamin B 12, folate, homocysteine levels will
      be studied.Urine methylmalonic acid along with TMS/GCMS will also be done as a part of this
      project. Other investigations will be done as per case profile. Any other investigation if
      done for the case as a part of the treatment or diagnostic evaluation like liver function
      tests, renal function tests , EEG, CT, MRI will also be recorded.

      The second section of the proforma consists of assessment of health and nutritional status of
      the mother. It aims at establishing any direct relation between the maternal health and
      development of ITS like picture in their children. Mother's dietary history will be taken to
      find out whether the maternal diet is lacking in Vitamin B12 and folate. A targeted
      neurological examination will be done to look for neurological manifestations of vitamin B12
      deficiency in form of posterior column tract sensation and presence of peripheral neuropathy.
      A lab estimation of maternal Vitamin B12,folate and homocysteine levels will also be done and
      recorded.

      Blood samples: Sampling would be done along with routine sampling as far as possible to avoid
      additional pricks to the child. Plasma would be immediately separated and stored and tested
      for Vitamin B12 ,homocysteine, methylmalonic acid and folate levels. This blood would be
      taken from sample already taken for other tests to be done in the child. Confidentiality of
      records would be maintained. The study is purely observational and will not influence the
      management of the child. Though as a standard policy all children with ITS would receive
      Vitamin B12, folate and other supplements and diet counseling will be done.

      Blood TMS-acylcarnitine and propionylcarnitine along with evaluation of urine methyl malonic
      acid as a part of GCMS will also be studied in cases and controls.

      Mother's blood samples will also be taken after explaining to them the entire aims and
      objectives of the study and taking full free voluntary informed consent from them. This would
      also benefit the mothers in a way because those identified with a deficiency will be given
      supplements to overcome the deficiency.

      Control samples will be taken from children of the same age group admitted for some other
      ailment. A 2 ml sample will be taken from sample already drawn for other tests to be done in
      the child. The controls also stand to be benefitted because all children found deficient will
      be advised Vitamin B12 and folate supplementation immediately.

      Vitamin B12 and folate levels will also be studied in the mothers of the 50 controls. All
      mothers found deficient will be advised Vitamin B12 and folate.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Hospital based study (Advanced Pediatrics Centre, PGIMER) all cases of infantile tremor
        syndrome (ITS) and pre ITS presenting to APC during the study period
      
Biospecimen description: 
      serum samples