A CASE OF STORAGE DISORDERA CASE OF STORAGE DISORDER

DR.K.INDU PRIYADIRECTOR’S UNIT

INSTITUTE OF SOCIAL PAEDIATRICSSTANLEY MEDICAL COLLEGE

CASE REPORT

4 ½ yrs male C/o cough , cold – 1 wk fever - 3 days Frequent URI since 1 ½ yrsH/o abd. Distension since 1 ½ yrs - insidious in onset - progressed to present sizeH/o swelling in the Rt groin- 2 ½ yrs - Cough impulse + - reduces on lying down

Perinatal period - uneventful.Development – speech delay, < 10 words - bowel control + - bladder control - - motor milestones N

4 1/26 1/2

31 28

3rd degree consanguinity

PEDIGREE CHART

ExaminationCoarse facies - coarse hair - frontal bossing - thick eyebrows - broad nose - thick upper lipsMild pectus

excavatumNo pallor

Vital signs – NAnthropometry Expected Wt. 16 kg 17 kg Ht. 95cms 102cms HC 52cms 50cms MAC 13cms

Systemic examination

CVS - normalRS - NVBS Bil. creps Bil. WheezeAbd. - distended Liver 9cms RCM - firm, span 15cms Spleen 2cms LCM,

firm Genitalia - Rt indirect inguinal hernia

CNS – Speech retarded -limited meaningful

words Turns to sound Motor system N Waddling gait +Spine - NEyes – Cornea clear - Slit lamp exam. N - Fundus N

Differential Diagnosis Hunter syndrome Sanfilippo syndrome Multiple sulfatase deficiency I cell disease

Investigations

CBC, RFT & LFT - NMantoux : –vePeripheral smear – NUrine analysis – NUSG Abd. – hepatospleenomegaly - echotexture N

X ray chest - thick oar shaped ribs - clavicles short & thick medially

( at 2 yrs )Thick cortexBullet shaped

phalangesMetacarpals –

pinched & pointed proximally

Medial facing radius & ulna forming V

Carpal bones – 2- Delayed bone age

X ray forearm & wrist ( 4 ½ yrs )

carpal bones – only 2

Thyroid profile - N

X ray skull - thick calvarium

-Oval shaped vertebral bodies-Inferior beaking of lower thoracic vertebra

Hypoplastic acetabulam

Urinary screening for GAG

CTAB test for Heparan SO4 - +ve CPC test for Heparan SO4 - +ve Acid alb. test for Dermatan SO4 - +ve Toluidine test for Chondroitin SO4 - +ve

Urinary GAG conc. By DMB test - elevated GAG : creatinine ratio

Urine for metabolic screening Tyrosinuria

Homogenstic acid Cystinuria Negative

PKU MSUD Galactosemia

Enzyme assay in plasma and leukocytes

- N acetyl glucosaminidase def.

SANFILIPPO SYNDROME

TYPE B

ECG , Echo – normal

CT Brain - normal

Treatment Given1.Respiratory inf. –symptomatic Rx

2.Herniotomy for inguinal hernia

3. No definitive Rx - supportive care

Discussion

MPS - lysosomal storage disorder. Group of 7 – I ,II,III,IV,VI,VII,IXDef. in enzymes needed to break down

GAG (GAG in extra-cellular matrix & cell surface)

All are AR except Hunter which is XLR

SANFILIPPO SYNDROME

Named after Sylvester Sanfilippo – 1963Hunter & Hurler – HS & DS +veSanfilippo - only HS +ve - Min. facial &

radiological features

INCIDENCESanfilippo

typeIncidence

A 1 in 1,00,000

B 1 in 2,00,000

C 1 in 15,00,000

D 1 in 10,00,000

GENETICS – AR inheritanceMPS III ENZYME GENE

locus

A Heparan S sulfamidase 17q25.3

B N Acetyl alpha glucosaminidase

17q21

C Acetyl Co A glucosaminide N acetyl transferase

8p11-q13

D N acetyl glucosaminine 6 sulfate sulfatase

12q14

Pathophysiology

Clinical features - progressive lysosomal accumulation of GAG - heparan sulfate

No racial or sex predeliction

HISTORYDevelopment in 1st 2 yrs - NCNS disease predominatesLess skeletal & somatic involvementMPS III – 4 types clinically indistinguishable - III A - most severe, early onset & rapid progression - III B - wider clinical heterogenecity - III C & D – intermediate forms

Onset b/w 2 to 6 yrsDevelopmental delay in infancy in someGrowth slows at 3 yrsBehavioural changes hyperactivity aggressive & destructive behaviourSleep disturbancesSpeech delayGait disturbances

MPS III contd.

Seizures may occur – controlled with medicationDecreased mental & physical abilities prevent

them from progressing in academics 10 yrs - limited activityChronic or recurrent diarrhea – accumulation of

GAG in neurons of myenteric plexusAirway obstruction – d/t anatomical changes thick secretions neurological impairmentRespiratory inf. & sinopulmonary disease

Physical findingsHead and face Coarse facies – coarse hair frontal bossing thick eyebrows broad nose thick lips Eyes – clear cornea

GI– hepatosplenomegaly Genitourinary inguinal hernia umblical hernia

Skeletal Mild dysostosis multiplex – constellation of

characteristic skeletal

changes in MPS Joint stiffnessNeurological Severe progressive deterioration Hearing loss Speech delay

InvestigationsDefinitive diagnosis Enzyme assay in cultured skin fibroblast peripheral blood leukocyteUrinary screening for GAG – HSPrenatal diagnosis Measuring specific enzyme activity in cultured amniocytes or chorionic villi

cells

Imaging

Skeletal survey to diagnose dysostosis multiplex

Echo – septal hypertrophy valvular disease

CT brain – hydrocephalus Changes in brain structureEEG – to detect seizure activityPolysomnography – obstructive sleep

apnea

TreatmentBMT not beneficialEnzyme replacement not successful - doesn’t cross BBBResearch on the way Supportive careParental education

MortalityDeath by 20 yrs airwary obstruction pulmonary infection

Support groups

Children Living with Inherited Metabolic Diseases (CLIMB )

National Organisation for Rare Diseases( NORD )

Alliance SanfilippoNational MPS Society

Rx FOR OTHER MPSAldurazyme for HurlerElaprase for HunterNaglazyme for Maroteaux Lamy

Mucopolysaccharidoses

Glycogen storage disorder

MPS kids lose a little more of their life each day.

Eventually they will lose their ability to walk, hear, see and even swollow their food.

After many medical problems, pains and suffering, supportive paediatric care is the only solace.

THANK YOU