Metabolic Disorders and SIDS

1
Metabolic Disorders and SIDS

• Dr Michael Cassidy
• Portiuncula Hospital
• Ballinasloe

2
Illustrative Case History

• 6 day old female, 1st child, FTND
• Uneventful pregnancy no medications, no
  infections, no alcohol/cigarettes
• No family history
• Home day 3
• Bottle fed/feeding well
• Day 6 appeared to fall asleep in car 10mins from
  home
• Could not be aroused on arrival

3
Autopsy Findings Gross

• Externally normal no dysmorphic features
• Normal external measurements
• Frothy fluid at nostrils
• Internal organs anatomically normal, incl.
  weights
• Lungs slightly congested
• Scanty epicardial visceral pleural petechiae
  --- no thymic petechiae

4
Autopsy Findings Microscopic

• Mild focal fatty change in liver
• Nil else
• Time of death 6.12 pm
• Autopsy 9.30 am

5
Postmortem Investigations

• Skeletal survey negative
• Viral screen negative
• Cell cultures for viruses (lung,myocardium)
  negative
• Cultures (CSF,blood,bronchi,lungs) negative
• Faecal culture examination for
  cryptosporidium,adenovirus,rotavirus negative
• Meningococcal DNA PCR screen negative
• No urine in bladder
• Chromosomes 46XX normal female

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Metabolic Causes of SIDS

• Main Groups
• Defects of fatty acid oxidation (FAO)
  ketogenesis
• Urea cycle disorders
• Organic acidurias
• Respiratory chain disorders/Congenital lactic
  acidosis
• Carbohydrate disorders

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FAOs most likely to present as SIDS (3-6)

• Medium chain acyl-CoA dehydrogenase (MCAD) 50
• Primarily a hepatic FAO
• 1/8000 NW Europeans
• 1st crisis fatal in up to 25
• Screening programmes US,Australia Europe
• 15 other FAOs 50
• Most are detectable by acylcarnitine profiling
• Subsequent fibroblast culture may be required

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Checklista. blood

• Guthrie card/ filter paper (neonate card)
• Electrospray ionisation tandem mass
  spectrophotometry
• Lithium Heparin 10 mls plasma -20C, cells 4C (
  acylcarnitine profiles, aminoacid profiles)
• EDTA 5 mls -20C DNA analysis
• Fluoride Oxalate 5 mls -20C intermediary
  metabolites (glucose, NEFA)

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Checklistb. Urine

• Plain tube -20C
• Organic acidurias

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Checklistc. Vitreous

• Fluoride Oxalate 5 mls -20C
• Organic acidurias / glucose

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Checklistd. Bile

• Guthrie Card/Filter Paper
• Plain tube -20C
• Acylcarnitine profiles

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Tissue for Biochemical Analysis

• Liver/myocardium/skeletal muscle/kidney
• Ideally within 4 hours
• Wrap in foil. Snap freeze. Store -80C

13
Tissue for Fibroblast Culture

• Culture medium, eg Hams
• Saline
• Small samples
• 2-3 days
• Pericardium/fascia/cartilage
• Store overnight 4C

14
Sources

• Ann Clin Biochem 2004 41 282-293
• Essentials of Autopsy Practice Recent Advances,
  London Springer-Verlag 2004 17-44
• Simon Olpin Dept. Clinical Chemistry, Sheffield
  Childrens Hospital, Sheffield, S10 2TH

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Biochemical Analysis

• Blood aminoacid profile Generalised
  aminoacidaemia, ? Significance, ? PM effect
• Guthrie card for acylcarnitine profile Temple St
  Hospital Gt Ormond St
• Raised propionyl carnitine butyryl carnitine
• Profile suggestive of disturbance in carnitine
  transporter activity

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Genetics

• Parents referred to clinical geneticist
• Counselled re recurrence risk ( ¼ )
• Request received for any frozen tissue samples or
  residual blood/plasma