Case presentation Dr Waceke - PowerPoint Presentation

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Case presentation

Dr

Waceke

N

Kombe

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HISTORY

M.H.N

Age: 1 year 3 months

C/O Abdominal Distension for 1

week. No yellowness of eyes, not easily fatigued, passing urine normally.

No vomiting, No

diarrhoea

. Feeding has been good.

Seen at

another hospital,

Ultrasound done and reported to show enlarged liver and spleen.

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HISTORY

Mother reports that she lost a sibling at 23 months of age who started to have Abdominal Distension and was diagnosed to have

hepatosplenomegaly

. An autopsy was done but the results were inconclusive.

One surviving sibling, 2years 8 months, no known medical conditions.

This is the first admission. Born at term. BWT 3.0Kg.

c/s due to a previous scar. She

walks with support.

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EXAMINATION

O/E low set ears with flat nasal bridge. No simian crease

. Short stature.

Current weight

10kg

Length

75.5cm

, H/Cir

45cm

at 2 years.

Apex beat 5

th

ICS MCL .

Normal heart sounds.

Abdomen looked distended uniformly. No scars, no superficial veins. Bowel sounds normal.

Hepatosplenomegaly

noted.

Liver 6-8 cm below costal margin. Spleen 4cm below costal margin. Difficult to assess for ascites. Normal bowel sounds.

Kidneys not palpable.

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Growth chart

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INVESTIGATIONS

FBC

Hb

9.8, MCV 57.1, MCH 18.9, PLT 134, WBC 6.98 (

L 1.9

,

N 3.93

).

HIV-

NEGATIVE

HEB B s Ag , CMV

Ig

M- NEGATIVE

No evidence of Beta Thalassemia or

Hemoglobinopathy

LFT’S

GAMMA

GT 47 (N=22)

AST 80 (N=48)

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INVESTIGATIONS

FERRITIN

141 (N=67)

U/E/C NORMAL

THYROID MARKERS NORMAL

ALPHA FETO PROETIN NORMAL

URINE REDUCING SUBSTANCES- NEGATIVE

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Abdominal ultrasound

The liver is grossly enlarged having a span of 13.3cm X 8.4cm X9.4 cm. Normal

echotexture

, intrahepatic bile ducts not dilated. Gall bladder is normal, no gall stones.

Spleen is markedly enlarged measuring 10.8 x 12.5x 9.82 cm. It has a normal

echotexture

, no obvious portal

varices

.

Adrenal, kidney and pancreas are normal. No bowel lesion seen. There is no ascites.

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BONE MARROW ASPIRATE

Patchy infiltration by large cells with abundant wrinkled cytoplasm, some multinucleated. Features of a

lysosomal

storage disease.

LIVER BIOPSY

Reactive hepatocytes with sinusoidal expansion by enlarged

Kupfer

cells with abundant wrinkled paper cytoplasm. Features

favour

Gauchers

Disease.

 

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ENZYME ASSAYS.

Beta

Glucosidase

activity in serum: not detectable. Deficient activity of beta

glucosidase

noted in leucocytes.

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What could this be?

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GAUCHERS DISEASE

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Lysosomal lipid storage disease.

One of the most common lysosomal storage diseases.

Autosomal recessive.

Incidence of Type 1(99% of cases) among Ashkenazi Jews 1-1000 live births; 1:50,000 European Jewish population.

3 clinical subtypes:

Type 1 – adult,

nonneuronopathic

form

Type 2- infantile or acute

neuronopathic

form

Type 3- juvenile or

subacute

neuronopathic

form

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Gaucher

disease results from the deficient activity of Glucosylceramide

β

glucosidase.

This results in the accumulation of the substrate glucosylceramide.

Accumulation occurs in the

reticuloendothelial

system. The progressive deposition results in infiltration of the bone marrow, progressive hepatosplenomegaly, and skeletal complications.

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Pathophysiology of Gauchers

disease

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GENETICS

Deficiency encoded by a gene located on chromosome 1q21-q31.

Four mutations account for approximately 95% of mutant alleles among Ashkenazi Jews.

N370S

L444P

84insG

IVS2+2

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CLINICAL MANIFESTATIONS TYPE 1

Age of onset- variable. Early childhood to adolescent.

Easy bruising- thrombocytopenia; chronic fatigue-

anaemia

; hepatomegaly, splenomegaly and bone pain.

Pulmonary involvement

Growth retardation

Bone pain, pathologic fractures,

pseudosteomyelitis

, lytic lesions,

osteosclerosis

, bone crises with severe pain

Radiologic evidence of skeletal involvement- Erlenmeyer flask deformity of the distal femur

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Erlenmeyer flask deformity.

Modelling abnormality.

So named because of its similarity to the glass flask invented by a German scientist.

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TYPE 2

Rare form

Rapid neurodegenerative course with extensive visceral involvement and death within the first years of life.

Presents in infancy with increased tone, strabismus, hepatosplenomegaly

Failure to thrive and stridor

Psychomotor regression. Death typically occurs secondary to respiratory compromise

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TYPE 3

Presents with clinical manifestations that are intermediate to those seen in types 1 and 2, with presentation in childhood and death by age 10-15 years.

More common among the Swedish population

Neurologic involvement is present.

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INVESTIGATIONS

Bone marrow. Will reveal

Gaucher

cells.

Enzyme assays.

Glucocerebrosidase

activity in isolated leucocytes or cultured fibroblasts.

Gene mutation identification

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WHAT IS A GAUCHER CELL

The 

Gaucher

cell

 results from the accumulation of excessive

glucocerebroside

in 

cells

 of the

monocyte-macrophage

system. 

Pushes the nucleus to the periphery

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TREATMENT

Enzyme replacement therapy. Recombinant human

glucocerebrosidase

. 60IU/kg IV infusion every other week. Reverses most symptoms (

organomegaly

, hematologic indices, bone pain)

Velaglucerase

alfa

Taliglucerase

alfa

Enzyme replacement does not alter the neurologic progression of patients with

Gaucher

disease types 2 and 3.

Oral substrate reduction agents-

miglustat

Bone marrow transplantation. Curative but associated with significant morbidity.