TY - JOUR
T1 - Clinical, biochemical and molecular diagnosis of a compound homozygote for the 254 bp deletion-8 bp insertion of the APRT gene suffering from severe renal failure.
AU - Di Pietro, Valentina
AU - Perruzza, Italia
AU - Amorini, Angela Maria
AU - Balducci, Alessandro
AU - Ceccarelli, Lia
AU - Lazzarino, Giuseppe
AU - Barsotti, Paola
AU - Giardina, Bruno
AU - Tavazzi, Barbara
PY - 2007
Y1 - 2007
N2 - Objective: To determine the type of mutation in a patient with clinical diagnosis of suspected APRT deficiency.
Design and methods: A 51-year-old male patient, with a clinical history of two prior episodes of renal colic with urinary stone excretion (reported
as uric acid stones in the first episode and as calcium oxalate stones in the second), was admitted to the hospital with severe non-oliguric renal
failure (1.06 mmol/L serum creatinine), severe hyponatremia (114 mmol/L Na+), metabolic acidosis (14 mmol/L HCO3
−) and uricemia in the normal
range. Abnormalities at renal scan and persistency of severe renal failure required to start haemodialysis. Results of renal biopsy prompted us to
undertake a biochemical and molecular biological evaluation of the patient for suspected adenine phosphoribosyltransferase (APRT) deficiency.
Results: HPLC analysis of serum and urine, for determining purine derivative profile, showed the pathological presence of adenine in both
biological fluids (3.57 μmol/L and 7.11 μmol/mmol creatinine in serum and urine, respectively; not detectable in both fluids in healthy controls).
APRT assay in a sample of patient hemolysate showed no detectable activity of the enzyme (25.56±9.55 U/L red blood cells in control healthy
subjects). Molecular biological analysis of the amplified APRT gene revealed that the patient harboured in exon 3 a homozygous 254 bp deletion–
8 bp insertion, previously described only once in a compound heterozygote. Analysis of the patient family showed that heterozygotes for this
APRT gene mutation, in spite of a 69% lower APRT enzymatic activity than that of healthy subjects, had no detectable adenine concentrations in
both serum and urine.
Conclusions: Results of the first patient harbouring the homozygous 254 bp deletion–8 bp insertion of the APRT gene strongly indicated that
definitive diagnosis of APRT deficiency (often under or misdiagnosed) would require a combined clinical, biochemical and molecular biological
evaluation.
AB - Objective: To determine the type of mutation in a patient with clinical diagnosis of suspected APRT deficiency.
Design and methods: A 51-year-old male patient, with a clinical history of two prior episodes of renal colic with urinary stone excretion (reported
as uric acid stones in the first episode and as calcium oxalate stones in the second), was admitted to the hospital with severe non-oliguric renal
failure (1.06 mmol/L serum creatinine), severe hyponatremia (114 mmol/L Na+), metabolic acidosis (14 mmol/L HCO3
−) and uricemia in the normal
range. Abnormalities at renal scan and persistency of severe renal failure required to start haemodialysis. Results of renal biopsy prompted us to
undertake a biochemical and molecular biological evaluation of the patient for suspected adenine phosphoribosyltransferase (APRT) deficiency.
Results: HPLC analysis of serum and urine, for determining purine derivative profile, showed the pathological presence of adenine in both
biological fluids (3.57 μmol/L and 7.11 μmol/mmol creatinine in serum and urine, respectively; not detectable in both fluids in healthy controls).
APRT assay in a sample of patient hemolysate showed no detectable activity of the enzyme (25.56±9.55 U/L red blood cells in control healthy
subjects). Molecular biological analysis of the amplified APRT gene revealed that the patient harboured in exon 3 a homozygous 254 bp deletion–
8 bp insertion, previously described only once in a compound heterozygote. Analysis of the patient family showed that heterozygotes for this
APRT gene mutation, in spite of a 69% lower APRT enzymatic activity than that of healthy subjects, had no detectable adenine concentrations in
both serum and urine.
Conclusions: Results of the first patient harbouring the homozygous 254 bp deletion–8 bp insertion of the APRT gene strongly indicated that
definitive diagnosis of APRT deficiency (often under or misdiagnosed) would require a combined clinical, biochemical and molecular biological
evaluation.
KW - APRT
KW - biochemical diagnosis
KW - clinical diagnosis
KW - molecular diagnosis
KW - APRT
KW - biochemical diagnosis
KW - clinical diagnosis
KW - molecular diagnosis
UR - http://hdl.handle.net/10807/28710
M3 - Article
SN - 0009-9120
SP - 73
EP - 80
JO - Clinical Biochemistry
JF - Clinical Biochemistry
ER -