Diagnosis and Management of children with Alstrom syndrome

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Diagnosis and Management of children with Alstrom
syndrome

• Timothy Barrett
• School of Clinical and Experimental Medicine
• College of Medicine and Dentistry
• University of Birmingham, UK
• t.g.barrett_at_bham.ac.uk
• March 2012

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Summary

• Case studies
• System assessments

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Child A White European family

• Healthy baby
• Photophobia, retinal dystrophy in infancy
• Obesity from infancy
• Deafness
• Struggled at school
• Diagnosed at 7 years
• Fatty Liver disease and glucose intolerance
• 13 years insulin resistant diabetes
• Heterozygous mutations in ALMS1

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Children B and C (S Asian, parents first cousins)

• Healthy babies, obese in infancy
• Diabetes at 6 months treated with tablets
• Rod-cone dystrophy but no photophobia
• Profound sensorineural deafness
• Seen in Alstrom clinic aged 8 and 10 years
• Not obese, not diabetic
• Sideroblastic anaemia in Sara aged 11 years
• Mutations in SLC19A2 gene (Rogers syndrome)

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Child D (South Asian, parents first cousins)

• Photophobia in first 3 months
• Cardiomyopathy
• Severe developmental delay with microcephaly
• Sensorineural deafness
• Slim, feeding difficulties
• Now aged 6 years, attends Alstrom clinic
• Homozygous ALMS1 mutation probable
  co-inheritance of microcephaly

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Child E (South Asian, parents first cousins)

• Obesity onset in infancy
• Retinal dystrophy in childhood, loss of night
  vision
• Mild learning difficulties
• Flat feet
• Extra digits removed at birth, when questioned
• Hyperechogenic kidneys on antenatal scan, now
  normal
• Homozygous mutation in BBS1

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Child F boy, white European parents

• Normal birth, failed hearing test sensorineural
  loss at high frequencies, now hearing aids
• BMI overweight but not obese
• No eye problems noted as a baby, no nystagmus
• Now aged 5 poor visual acuity, sunlight hurts
  eyes
• Mild learning difficulty
• Family history of diabetes on Mothers side
• On examination, possible dental enamel problem
• Initial Alstrom screen negative

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Who gets genetic testing?
DD Alstrom, Bardet Biedl, TRMA, Lowes, others
? Add photophobia
Consider co-inherited diseases
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Who gets genetic testing in childhood?
Infancy onset retinal dystrophy with photophobia
Infancy onset cardiomyopathy
Relative with Alstrom syndrome
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What needs to be offered at MDT annual clinics?
AS-UK
Ophthalmology
Endocrine
Cardiology
Counselling
Dietetics
CNS
Genetics
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Paediatric cardiology

• Annual ECG look for heart strain, abnormal
  rhythm
• Annual Echocardiogram wall movement
  abnormalities
• ? Blood test for brain natiuretic peptide
• ? Cardiac MRI
• Decision on whether/when to add in medicines

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Vision assessment

• Ophthalmology referral usually done locally. We
  will offer at BCH if local provision inadequate.
• Progressive loss of vision over childhood
• Potential for cataracts but significance?
• Low vision aids
• Early development of low vision skills
• Preparation for college for the blind
• Career counselling

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Dietetics

• Annual BMI, body composition by bioimpedance
• Completion of food diary
• Dietetic advice
• Healthy eating protein, carbohydrate, fat,
  vitamins and minerals to allow healthy growth
• Calorie intake to same age child of average
  weight
• Exercise advice
• Within limits of mobility, vision
• ? Does fat mass reduction help insulin resistance?

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Clinical psychology support

• Identifying emotional or behavioural issues
• Both child and parents
• Need for CAMHS referral?
• Need to liaise with SENCO at school?
• Follow-up local children ongoing care
• Follow-up other children Liaise with local
  clinical psychology services

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Physiotherapy

• Assessment of mobility, posture
• Teaching posture and exercises
• Mostly positional upper spine kyphosis,
  correctable with posture training
• Occasional kyphoscoliosis
• No clear enthesitis in children

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Hearing assessment

• Audiometry
• Classically high tone sensorineural deafness
• Progressive
• Hearing aids in school
• ? Repeated every 2 years
• Mostly done locally but we do offer at BCH if not
  done within last 2 years

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Diabetes mellitus

• Progression of insulin resistance to type 2
  diabetes
• Screen from puberty (10yrs) with HbA1c, fasting
  glucose.
• If abnormal, then home blood glucose monitoring.
• ? Should we do glucose tolerance tests?

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Endocrine/metabolic

• Puberty look for delayed puberty gt14yrs girls,
  gt16yrs boys
• Thyroid Baseline at diagnosis.
• Liver function annually
• Fasting lipids and cholesterol annually
• ? Should we screen for thyroid disease more
  frequently?

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Renal

• Annual renal function urea, creatinine
• Ambulatory blood pressure monitoring
• Early morning urine for albumin creatinine ratio
• If raised, then repeat x 2.
• ? Need to audit ambulatory blood pressure
  monitoring

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Bladder function

• History of bedwetting, accidents
• First optimize glucose control
• Exclude or treat infections, ? diabetes insipidus
• Urodynamic assessment
• Bladder volumes, detrusor muscle instability

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Other

• Respiratory?
• Dermatology
• ENT

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Thankyou!

• Lead paediatric service Timothy Barrett
• Clinic administrator Lesley Porter
• Paediatric cardiologist Ashish Chikermane
• Paediatric diabetes specialist nurse Kirsty
  Mobberley
• Paediatric Dietician Hazel Riggall
• Clinical Psychologist Jenny Allman
• Physiotherapy Liz Wright, Gemma Mears
• Genetics Denise Williams