Prepared by Porf. Dr. Hosny Salama Unit

Presented by Dr. Shereen Abdelaleem.

Click here to download a power point presentation for the case.

Click here to download a power point presentation for the postgraduate presentation about Alagille Syndrome by Dr. Wael Fathy.

Staff of the Unit:

Prof. Dr. Hosny Salama

Prof. Dr. Eman Medhat

Assisst Prof. Hanan Abd El Heleem

Dr. Rasha Ahmed

Dr. Wael Fathy

Dr. Zeniab Zakaria

Dr. Mohamed Orfi

Dr. Mohamed Ebeid

Resident Aisha El Sharkawy

Resident Shereen Abd El Alim

Resident Tahany Hussien

Alagille Syndrome

Personal history

Male Patient , 22 years old , Single , Born and still Living in Shoubra , He is a worker in a factory . Smokes 3 Cigarettes per day for 7 years .

There is no History of drug or alcohol intake .

There is no History of contact with Canal Water or antischistosomal Treatment .

Complaint

Yellowish discolouration of eyes.

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Present history

• The Condition started 3 days after birth by jaundice as noticed by his mother for which she saught medical advice in hospital & she was told that it was neonatal jaundice & it would subside but it did not subside .

• It was associated with intermittent attacks of dark colored urine , normal colored stool .

• The condition remained stationary all through with persistent jaundice & no other complains

• 4 Years ago He started to develop attacks of Pruritus affecting Extremities day and night with remission &exacerbation , associated with deepening of jaundice .

• 3 Years ago He was admitted to Arab contractors hospital and Liver Biopsy was done and showed chronic hepatitis to which the patient received symptomatic ttt with no improvement .

• The Condition was not associated with Right hypochondrial pain , Abdominal distension , L.L Oedema , Bleeding Tendency , Haematemsis , Melena , or DCL .

• No symptoms suggestive of other systems affection.

Past history

• Pre-natal: no drug intake , no fever.

• Natal: normal vaginal delivery with no complications .

• Post-natal:

  • Delayed milestone

  • Diminution of hearing due to CSOM

  • No convulsion

  • No blood transfusion

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Family history

• -ve Consanguinity

• No similar condition in the family .

General examination

The patient is conscious , lies comfortably in bed & with average intelligence

Complexion: broad forehead , flattened nose , pointed chin ( Triangular face ) , his father has the same facies.

Pulse: 88\min – regular.

Blood pressure: fluctuate from 120/80 – 140/90.

Temp.: 36 c ( afebrile during hospital stay )

Head and Neck:

tinge of jaundice

no cyanosis

no pallor

no xanthomas

no parotid gland enlargement

no thyroid gland enlargement

Lymph Node:

no lymph node enlargement

Limbs:

scratch marks in upper limbs and lower limbs

roughness & hypopigmentation

no clubbing , no spider naevi , no flapping tremors ,no palmar erythema

no lower limbs oedema

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Abdominal examination

Shape: normal shape and contour .

Subcostal angle: wide

Recti: Divarication of recti

Umbilicus: shifted downwards , normal shape , no impluse on cough .

No visible or dilated Abdominal wall veins . No scars , pigmentation , or hernias .

Liver :

Upper border is detected in 5th space MCL

RT. Lobe is 4 cm from costal margin in MCL

LT .Lobe 8 cm from xiphisternum in mid line

Surface: Smooth

Consistency: Firm

Edge: Sharp

Tenderness: Not Tender

Spleen :

It is felt 16 cm from costal margin

Surface: Smooth

Consistency: Firm

Tenderness: Not Tender

No ascites detected clinically

Cardio –Vascular System

Inspection: Free

Palpation: Free

Percussion: Free

Auscultation: Muffled Second Sound P. Early Systolic Murmur P

Chest and Neurological Examination

FREE  

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E.S.R

•  First hour: 80 mm/h

•  Second hour: 110 mm/h

{N. Male : 3 –5 mm/hour}

C.B.C

WBC : 3.4 L 10^3 /Ul .

ST. : 4 % .

SEG. : 49 % .

BASO. : 1 % .

ESINO. : 14 % .

LYMPHO. : 20 % .

MONO. : 12 % .

HGB : 12.2 g/dl .

MCV : 92.9 fl .

MCH : 31.0 pg .

PLT : 110 L 10^3/ul .

• Mild normocytic normochromic anemia

• Mild leukopenia

• Mild monocytosis

• Moderate eosinophilia

• Mild thrombocytopenia

Picture of Pancytopenia

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Liver biochemical profile

Prothrombin Time and Conc.

Prothrombin Time = 14.5 sec

Control = 13.0 sec

Concentration = 85 % . {N. 75 – 120%}

INR = 1.15

Urine analysis , Urea , Creatinine Serum Sodium , Serum potassium Fasting Glucose , 2h.pp. Sugar Within Normal Range .

Abdominal ultra-sound

•  Liver : Enlarged in size with coarse texture, finely irregular surface and mildly attenuated hepatic veins , no focal lesions or IHBR dilatation , P.V is not dilated .

•  Gall bladder : Average size and wall thickness no stones or mud inside . CBD is not dilated.

•  Spleen : Enlarged (Longest axis is >20 cm ) homogenous echopattern.

•  Kidneys : Right Kidney measures 9 x 3.5 cm. Cortical thickness is 1 cm . - Left Kidney measures 7.3 x 2.4 cm . Cortical thickness is 7 mm . Both are of normal parenchymal echogenicity no typical calculi , cyst or back pressure changes.

•  Pancreas: free.

•  No ascites.

•  Conclusion :

• Diffuse hepatic parenchymal pathology with early cirrhotic changes.

• Splenomegaly.

• Small sized Left Kidney.

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Doppler study on renal arteries

•The Lt. Kidney showed : PSV = 28 cm /sec . MDV = 12 cm /sec.

•Resistive index = 57 %

•PSV of aorta = 41 cm /sec .

•RA ratio = 0.7

•Similar finding are found in the Rt. Kidney .

•These findings are against diagnosis of renal artery stenosis .

For more confirmation isotopic scanning is recommended .

Differential Diagnosis

• Viral hepatitis

• Autoimmune hepatitis

• Gilbert`s syndrome

• Rotor`s syndrome

• Dubin –Johnson syndrome

• Haemolytic jaundice

• Wilson`s disease

• Cystic fibrosis

• Haemochromatosis

HEPATITIS MARKERS

• Hbs Ag = Negative

• Hbs Ab = Negative

• HB Core Total = Negative

• HCV Ab = Negative

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AUTOIMMUNE PROFILE

- ANA = Negative .

- ASMA = Negative .

- AMA = Negative .

- APA = Negative .

- Anti.L.K.M Antibodies = Negative .

- Serum Iron = 147 ug /dl { 59 – 158 }

- TIBC = 384 ug / dl {274 – 385 }

- Ferritin = 304 ng /ml { 28 – 397 }

- Ceruloplasmin = 0.35 g /l { 0.2 – 0.6 }

- Serum CU &Urinary CU ( not available )

- Alpha 1 Antitrypsin = 125 { 90 – 200 }

Ophthalmological Examination ( Slit Lamp Examination )

No Kayser - Fleischer ring

Hemolytic Profile

- Reticulocytes : 0.3 % .

- LDH = 527 u /l { 240 – 480 }

- Haptoglobin = 119 mg /dl {30 –200 }

- Hb Electropheresis = Normal .

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What are the possibilites ???

The most 2 common causes are:

• Alagille Syndrome

• PFIC

Lipid Profile

Cholesterol = 131 mg /dl {50 – 200 }

Triglycerides = 97 mg /dl { 0 - 149 }

HDL = 42 mg /dl { 40 –75 }

LDL –C = 70 mg /dl {100 –130 }

CHO /HDL = 3.1 % { 3.5 –5.5 }

Ophthalmological Examination

Anterior segment examination revealed bilateral Temporal persistent posterior embryotoxon . ( Slit Lamp Examination )

Fundus examination revealed bilateral Tigroid Fundus and optic nerve head drusen .

Ophthalmological U/S

B.A scan of both eyes shows :

• Axial length +22.0mm with normal ocular contour

• Normal ocular scan

• ONH drusen is positive in the right eye II

X-ray Lumbodorsal Spine

Plain X –ray of Lumbar Spine revealed :

• Good alignment of the Lumbar spine with preserved Lordosis

• Normal architecture of the vertebral bodies and their appendages

• Disc spaces are preserved

• Straightened Lumbar Lordosis

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Echocardiology Report

Normal Left Ventricular internal dimensions with normal overall systolic &diastolic functions

No obvious regional wall motion abnormalities could be detected at rest study

No masses could be seen inside the left ventricular cavity

Normal mitral valve thickness , structure & excursion. No stenosis or regurge

Normal left atrial dimensions with no masses seen inside its cavity by TTE

Normal pliadle trileaflet aortic valve with no regurge No stenosis

Normal right sided chambers dimensions with normal RV systolic function

Normal pericardial thickness . No effusion

There is possible osteal mild degree of stenosis is seen affecting the left main pulmonary artery branch Peak systolic gradient across the LPA is 30 mmHg.

Liver Biopsy

Gross : Two cores of needle biopsy specimen 1.5 cm length ,totally submitted .

Micro : Microscopic examination of the specimen revealed liver tissue with preserved lobular architecture . Three portal areas were only detected in the specimen , two of them were apparently hypoplastic &devoid of bile ductal structures ; they mildly infiltrated by minimal number of mononuclear inflammatory cells &fibrosis was absent . The hepatocytes were arranged in regular thin plates within the lobules , they showed minimal focal intracellar cholestasis mostly in periportal areas , minimal foci of pericellular inflammatory cellular aggregation , minimal number of apoptotic (acidophilic) bodies ;and their cytoplasm was free of P.A.S +ve diastase resistant globules .Canalicular and ductal cholestasis was absent. Centrilobular sinusoidal dilatation was also seen .

DIAGNOSIS:

THE FINDINGS ARE SUGGESTIVE OF PAUCITY OF THE INTERLOBULAR BILE DUCTS

THANK YOU

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