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@bham.ac.uk
March 2012
Summary
• Case studies
• System assessments
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
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)
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 coinheritance of microcephaly
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
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 Mother’s side
• On examination, possible dental enamel problem
• Initial Alstrom screen negative
Who gets genetic testing?
DD Alstrom,
Bardet Biedl,
TRMA,
Lowe’s,
others
Chilhood retinal
dystrophy
One of
Normal weight
Obesity Diabetes
Normal heart,lipids and
glucose tolerance
High blood lipids
Cardiomyopathy
Test for AS gene
Consider co-inherited
diseases
No test unless typical
features develop
? Add
photophobia
Sibling uncle, aunt or
cousin with Alstrőm
syndrome
Test for AS gene
Who gets genetic testing in childhood?
Infancy onset retinal
dystrophy with
photophobia
Infancy onset
cardiomyopathy
Relative with Alstrom
syndrome
What needs to be offered at MDT annual
clinics?
AS-UK
Ophthalmology
Endocrine
Cardiology
Dietetics
Counselling
CNS
Genetics
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
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
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?
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
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
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
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?
Endocrine/metabolic
• Puberty: look for delayed puberty: >14yrs girls,
>16yrs boys
• Thyroid: Baseline at diagnosis.
• Liver function: annually
• Fasting lipids and cholesterol: annually
• ? Should we screen for thyroid disease more
frequently?
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
Bladder function
• History of bedwetting, accidents
– First optimize glucose control
– Exclude or treat infections, ? diabetes insipidus
• Urodynamic assessment
– Bladder volumes, detrusor muscle instability
Other
• Respiratory?
• Dermatology
• ENT
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