HUNTER SYNDROME MUCOPOLYSACCHARIDOSIS TYPE

II

Authors: Meliţ Lorena Elena – MD, Pediatrics resident

Mărginean Maria, 3rd year of General Medicine

Scientific supervizor: Lecturer Dr. Duicu Carmen

Definition: Hunter syndrome, or mucopolysaccharidosis type II (MPZ II), is a lysosomal storage disease, caused by a deficient, or absent enzyme, iduronate-2-sulphatase. 

The syndrome has X-linked recessive inheritance.

The accumulated substrate in Hunter’s syndrome is heparan sulphate and dermatan sulphate.

EPIDEMIOLGY AND INCIDENCE

2,000 people afflicted with Hunter syndrome worldwide

500 of whom live in USA

incidence among males of approximately 1 in 130.000 male live births (study performed in United Kingdom)

8 cases in Romania (the present case= the 77thth)

SIGNS AND SYMPTOMS

first symptoms: abdominal hernias, ear infections, runny noses and colds

distinctive coarseness in the facial features: prominent forehead, a nose with a flattened bridge, enlarged tongue

thickening of the heart valves and walls, obstructive airway disease, large liver and spleen, joint stiffness, ivory-colored skin lesions

mental retardation

DIAGNOSIS

time of diagnosis: 2 to 4 years of ageclinical diagnosisadditional laboratory test: the idorunate-

2-sulfatase activity in serum, white blood cells, or fibroblast from skin biopsy

genetic test: mutation in the iduronate sulphatase gene

laboratory screening test: urine test for GAG (low sensibility)

TREATEMENT

palliative treatment: surgery, psychiatry, physiotherapy

bone marrow graft and hematopoietic stem cell transplantation - interventional risk, no influence on cognitive deterioration

Idursulfase (Elaprase) – enzyme replacement treatment (a purified form of the lysosomal enzyme iduronate-2-sulphatase)

experimental treatment: intrathecal injections of a more concentrated dose of Idursulfase

CASE REPORT

A 2.7 year-old boy admitted in 2012 in The Emergeny Clinical Hospital for Children-Cluj Napoca with the suspicion of a storage disorder

The first suspicion of a storage disorder was revealed around the age of 2-in Pediatric Clinic from Tg Mures based on clinical features!- the parents refused to believe it- they came back 8 months later when they were sent to Cluj Napoca for diagnosis confirmation

Past medical history: recurrent respiratory tract recurrent respiratory tract infectionsinfections and frequent ear infectionsfrequent ear infections.

CLINICAL EXAMINATION

high stature high stature (SDS+3,46)

moderately overweight (+25.97% on his height)

short neck

coarse facial features, prominent forehead, depressed nasal bridge

CLINICAL EXAMINATION

small stubby fingers with flexion of distal interphalangeal joints, joint stiffness

protruding abdomen with umbilical hernia

enlarged liver and spleen

mild mental retardation

PARACLINICAL TESTS

Cl. Mainz plasma iduronat sulphatase= 6, 7986 nM/ml/24h (NV = 300 – 800)

Cl. Rostock: plasma iduronat sulphatase = 1,3 µmol/l/h (NV ≥2 )

Gene IDS: intron 3 (c.419-2A>G)-hemizygote mutation fist and hand radiography: bone age adequate for 2 years

old, faced methaphises thoracal radiography: without pleuro-pulmonar modifications,

no radiological modifications in the heart, slimmer costal arcs at vertebrocostal joints

spinal column radiography: bent for superior angled lumbar kyphosis, lumbar paravertebral bodies with an anterior aspect of beak

radiography of the pelvis: ‘chalice’ shaped pelvis with iliac bones more developed than the ischiopubiens, horizontal cotiloid brow, deformed, bent for bilateral coxofemoral contortion, more obvious on the left. Bilateral coxa valga.

PARACLINICAL TESTS

forearm and hand radiography: forearm bones with shorter diaphysis without other modifications, metacarpal bones with angular diaphysis, distal phalanges in flexion. Bone age corresponding for 3 years old. Suggestive aspect for MPZ II.

echocardiography: Aortic Insufficiency-first degree. Mitral Insufficiency-first degree. Light ventricular hypertrophy.

abdominal ultrasound: Small enlargement of the liver and spleen.

eye bottom exam: contracted papilla with a small central excoriation in the right eye, normal vassal caliber, free macula, without reflex, thin retina with the visibility of the choroidian array.

oto-rhino-larynx exam: no pathological aspects

blood tests – biochemistry and hematology: normal values, less the immunogram: Ig A level= 0

DIAGNOSIS

Mucopolysaccharidosis type II

Moderate psychical retardation

Craniofacial dismorphism

Aortic insufficiency I degree

Mitral insufficiency I degree

Light ventricular hypertrophy

TREATMENT

Life dietary according to age

Substitutive enzyme treatment with Elaprase (iduronate-2-sulphatase) 0,5 mg/kg/dose/week, 1 PEV once a week

EVOLUTION and PROGNOSIS

Weekly treatment with Elaprase in the Pediatric Clinic of Tg. Mures Emergency County Hospital

Clinical examination every week – favorable evolution under substitutive enzyme treatment

Psychiatric evaluation: some small progresses were noticed, but generally his psychic status is stationary

Paraclinical tests – 26th of February

ALPH

227 U/L

Ca

2.16 mmol/L

Ir

14.36 µmol/L

AST

23.2 U/L

ALT

13.3 U/L

IGA-2

3 mg/dL

IGG-2

799 mg/dL

IGM-2

82 mg/dL

LDH

212 U/L

Mg

0.69 mmol/L

Urea

17.4 mg/dL

BIOCHEMISTRY

Erythrocytes sedimentation rate = 5 mm/h

WBC

6 590/µL

NEUT

2 670/µL

LYMP

3 190/µL

MONO

380/µL

EO

33O/µL

BASO

20/µL

HGB

11.7 g/dL

HCT

33.0 %

MCV

75.0 fL

MCH

26.6 pg

MCHC

35.5 g/dL

RDW-CV

13.0 %

RBC

4 4000*10³/µL

PLT

212*10³/µL

HEMATOLOGY

Paraclinical reevaluation

Abdominal ultrasound (23.04.2014): moderate enlargement of the liver and spleen. (Senior Lecturer Dr. Mărginean Oana)

Ecocardiography (30.04.2014): minor aortic insufficiency, minor mitral insufficiency. (Dr. Muntean Iolanda)

PROGNOSIS

Even though the evolution is stationary, the prognosis of this patient is not a good one because unfortunately, Hunter syndrome is a chronic disease without any curative treatment.

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