TYROSINEMIA

BRIEF DESCRIPTION
Tyrosinemia type I

• deficiency of Fumarylacetoacetatehydrolase
PATIENT HISTORY
Parent’s/Relative Background
• Patient has first degree consanguineous parents.
• Paternal uncle died at the age of 8 months with no known cause.

Medical History
• Upper Respiratory Tract Infection – 1 week before admission
PHYSICAL EXAMINATION
• sick, pale, jaundiced and drowsy
• weight and length were 7.5kgm and 69cm comparative with 10th and
25th percentile of his age respectively
• wide anterior fontanel (3x4cm)
• broadening of the wrists
• mild lower limb edema
• fine crackles were audible bilaterally on the chest
• abdomen was distended with everted umbilicus
• liver was palpable 5cm below right costal margin and 7cm span, with
irregular firm surface and it was not tender
• spleen was just palpable below left costal margin
SIGNS AND SYMPTOMS
• daily attacks of neurological crises in bouts of irritability
• crying with increased tone
• markedly increased tone in lower limbs
• deep tendon reflexes in the lower limbs
• drowsy with poor vision
• positive shifting dullness test for ascites, with scrotal edema and
normal male genitalia
REASON FOR COMING IN THE ER
The complaints of the patient which led to admission were:
• Abdominal Distension
• Fever
• Jaundice
• Melena
• Disturbed Level of Consciousness for 3 days
GENETIC ASSESSMENT
Tyrosinemia Type I

• autosomal recessive metabolic disorder

• gene is mapped on long arm of chromosome 15
LABORATORY DIAGNOSIS

CBC showed that the Hb. level was 8gm/dl, platelets count was
28.000/cmm, RBC: 3.3x106 /cmm, WBC: 4.8x103 /cmm (N.: 43%, L: 55,
M: 2%). ESR was 12mm and CRP was positive (>0.8ug/dl). Urine
examination showed aminoaciduria , albuminuria & RBCs
LABORATORY DIAGNOSIS

Blood phenylalanine, tyrosine and methionine levels were 269mol/L

(N.: 37-129), 897mol/L (N.: 32-275) and 897mol/L (N.: 32-275)
respectively. Urine examination for organic acids, showed increased
levels of succinylacetone, P-hydroxyphenylacetate, P-
hydroxyphenylpyruvate levels.
LABORATORY DIAGNOSIS
The left wrist graphy showed evidence of rickets. Abdomen
ultrasonography revealed hepatosplenomegaly with moderate ascites.
Liver examination showed multiple hyperechoic masses. Abdominal CT
showed hepatomegaly with multiple rounded hyperdense masses of
varying size, splenomegaly and ascites (Figs. 5 & 6). CT brain showed
marked bifrontoparietal cerebral atrophy.
JUSTIFY THE DIAGNOSIS
• The increased levels of serum tyrosine and methionine and urine succinyl
acetone provided the key for diagnosis.
• Our patient whose complaints started at eight months of age was reported to
have no complaints previously. He presented with bleeding, hepatomegaly,
neurological crises and clinical, laboratory and radiological evidence of rickets.
Laboratory studies revealed prolonged PT, PTT, low level of fibrinogen and
high FDP level.
• The infant was diagnosed as tyrosinemia type I and was prescribed a
phenylalanine and tyrosine restricted diet (special formula milk). Then he was
also enrolled in 2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione
(NTBC) treatment program with calcitriol and phosphorus solution for Vit.
JUSTIFY THE DIAGNOSIS
• The increased levels of serum tyrosine and methionine and urine
succinyl acetone provided the key for diagnosis.
• Our patient whose complaints started at eight months of age was
reported to have no complaints previously. He presented with
bleeding, hepatomegaly, neurological crises and clinical, laboratory
and radiological evidence of rickets.
• Edema
• Ascites