Developmental Disabilities Following a Diagnosis of a Metabolic Disorder in Children Aged 310 Years

1
Developmental Disabilities Following a Diagnosis
of a Metabolic Disorder in Children Aged 3-10
Years

• Kim Van Naarden Braun, Marshalyn Yeargin-Allsopp,
  
• Diana Schendel, Paul Fernhoff
• National Center on Birth Defects and
  Developmental Disabilities
• Centers for Disease Control and Prevention (CDC)
• Atlanta, Georgia

2
Introduction

• Newborn blood-spot screening is one of the
  largest population-based prevention programs in
  the US.
• Goal prevention of serious medical conditions
  and developmental consequences, e.g. mental
  retardation.
• No mechanism in the US for systematic
  surveillance of developmental status of children
  who screen positive for a metabolic disorder.

3
Methods

• This study utilized 3 data sources in Georgia
• Metropolitan Atlanta Developmental Disabilities
  Surveillance Program (MADDSP)
• Special Education Database of Metropolitan
  Atlanta
• State of Georgia Newborn Blood-Spot Screening
  Program (NBSP)

4
Methods
Metropolitan Atlanta Developmental Disabilities
Surveillance Program, MADDSP

• Established in 1991, an ongoing system, for
  monitoring the prevalence of selected
  developmental disabilities
• Multiple source record review
• MADDSP surveillance definition for MR IQ of ? 70
• Prevalence rate of MR in MADDSP, 1991 8.7/1,000

5
Methods
Special Education Database of Metropolitan
Atlanta

• Data are collected on all children who attend
  special education classes at any point during
  their schooling.
• IEP exceptionality categories such as
• significant developmental delay, learning
  disability, speech impairment, speech language
  impairment, and autism.

6
Methods
State of Georgia Newborn Blood-Spot Screening
Program, NBSP Division of Medical Genetics,
Department of Pediatrics, Emory University School
of Medicine and Georgia Department of Human
Resources Laboratory

• Identifies all newborns who screen positive for
  one of 7 metabolic and endocrine disorders
  screened for in Georgia.
• Reports annual and cumulative incidence rates for
  each of the metabolic/endocrine newborn screening
  tests
• 1) PKU, 5) Congenital Hypothyroidism,
• 2) Galactosemia, 6) Maple Syrup Urine Disease
  (MSUD),
• 3) Tyrosinemia, 7) Homocystinuria
• 4) Congenital Adrenal Hyperplasia

7
Methods

• Linkage of
• MADDSP and Special Education Database with
  NBSP
• Algorithms using child identifiers (e.g. first
  last name, date of birth) were used to identify
  children in both the NBSP and MADDSP or the
  Special education data.
• Criteria
• Analysis 1
• NBSP MADDSP born between 1981-1991 whose
  mother was a resident of the 5 county- metro
  Atlanta area at the time of the childs birth.
• Analysis 2
• NBSP Special Education data born between
  1981-1996 whose mother was a resident of the
  5-county metro Atlanta area at the time of the
  childs birth.

8
Methods

• Analyses 1 2
• Matches were independently reviewed by a
  pediatric geneticist and a developmental
  pediatrician.
• This process excluded any children for whom their
  developmental disability may be attributable to
  an etiology other than the metabolic disorder.

9
Results

• Analysis 1 Children with mental retardation
• Fourteen children in MADDSP with a positive
  screening test result
• 9 with congenital hypothyroidism,
• 3 with classic galactosemia,
• 1 with MSUD,
• 1 with tyrosinemia.
• 3 of the 14 children, 2 with classic galactosemia
  and 1 with MSUD, had MR that was attributed to a
  metabolic disorder.

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Results Analysis 1
Observed and expected number of children with
mental retardation (MR) following a positive
result on a screening test for selected metabolic
disorders- metropolitan Atlanta, Georgia, birth
years 1981-1991.

• Observed no. Expected no.
• Metabolic Disorder Rate1 children with
  MR2 children with MR3
• Phenylketonuria 6.2 0 23
• Homocystinuria 0.3 0 1
• Maple syrup urine disease 0.8 1 3
• Tyrosinemia (familial) ---4 0 0
• Hypothyroidism
• (primary congenital) 20.3 0 74
• Galactosemia 12.8 2 47
• 1Average annual birth prevalence rate in Georgia,
  1981-1991 per 100,000 children
• 2Based on MADDSP (MRmental retardation, IQ lt70)
• 3Based on the birth prevalence in GA and the
  number of live-born infants of residents of
  metropolitan Atlanta, 1981-1991.
• 4Number of cases familial tyrosinemia during
  1981-1991

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Results

• Analysis 2 Children with developmental delays
• Twenty-two children in special education with a
  positive screening test result
• 11 with congenital hypothyroidism
• 8 with variant galactosemia (DG)
• 2 with classic galactosemia (GG)
• 1 with MSUD
• 20 of the children had a developmental delay,
  requiring special education services,
  attributable to a metabolic disorder

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Results Analysis 2

• Observed and expected number of children with
  developmental delays following a positive result
  on a screening test for selected metabolic
  disorders- metropolitan Atlanta, Georgia, birth
  years 1981-1996.
• Observed no.2 Expected no.4
• Metabolic Disorder Rate1 SDD LD
  S /or L B Autism 3
• Hypothyroidism 23.0 1 1 5
  0 2 129
• (primary congenital)
• Galactosemia
• Classic (GG) 2.6 1 1
  0 0 0
  15
• Variant (DG) 11.0 0 1
  6 1 0 62
• Maple syrup urine disease 0.8 1
  0 0 0
  0 5
• 1Average annual birth prevalence rate in Georgia,
  1981-1996 per 100,000 children
• 2Based on special education data that did not
  meet MADDSP case definitions
• 3 Primary exceptionality SDD significant
  developmental delay, LD learning delay, S /or
  L speech and/or language,
• B behavorial disorder.
• 4 Based on the birth prevalence in GA and the
  number of live-born infants of residents of
  metropolitan Atlanta, 1981-1996.

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Summary

• Efficacy of newborn screening program.
• Underscores the importance of early
  identification and treatment of children with
  metabolic disorders to prevent or lessen the
  severity of serious neurodevelopmental sequelae.
• Need to conduct surveillance of developmental
  status of children who screen positive for a
  metabolic disorder to evaluate screening program.
  

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Summary

• Surveillance would facilitate efforts to
  determine the effectiveness of treatment and
  metabolic control.
• Population-based evidence of
• Speech and language delays in children with DG
  galactosemia
• Significant developmental delays, speech and/or
  language delays and autism in children with
  congenital hypothyroidism.

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Strengths

• Only ongoing surveillance of developmental
  disabilities for children diagnosed with a
  metabolic disorder in the US.
• High level of case ascertainment.
• Limitations
• Must have survived to age 3 years and must have
  lived in the 5 county area at that age or later.
• Clinical data on children with less severe
  developmental disabilities were limited.

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Future Activities

• Ongoing surveillance with linked systems
• Further investigation into metabolic control and
  course of treatment in children who were
  identified with developmental delays.