1. 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

2. Summary Case studies System assessments

3. 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

4. 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)

5. 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

6. 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

7. 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

8. Who gets genetic testing? Chilhood retinal dystrophy One of Obesity Diabetes High blood lipids Cardiomyopathy Test for AS gene Normal weight Normal heart,lipids and glucose tolerance No test unless typical features develop Sibling uncle, aunt or cousin with Alstrőm syndrome Test for AS gene DD Alstrom, Bardet Biedl, TRMA, Lowe’s, others ? Add photophobia Consider co-inherited diseases

9. Who gets genetic testing in childhood? Infancy onset retinal dystrophy with photophobia Infancy onset cardiomyopathy Relative with Alstrom syndrome

10. What needs to be offered at MDT annual clinics? Endocrine Ophthalmology CounsellingDietetics Genetics AS-UK CNS Cardiology

11. 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

12. 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

13. 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?

14. 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

15. 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

16. 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

17. 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?

18. 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?

19. 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

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

21. Other Respiratory? Dermatology ENT

22. 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