clinical case: 17-04-2012...may 17, 2013 · clinical case: 17-04-2012 carlos mejía chew mir 2 ....
TRANSCRIPT
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Clinical case: 17-04-2012
Carlos Mejía Chew
MIR 2
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34 Y/O MALE HIV+ PATIENT WITH HYPOPHOSPHATEMIA
AND GLUCOSURIA
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Past medical history • Multiple episodes of gonococci urethritis
• Acuminated condylomas 2003
• Atopic dermatitis
• Sept 2005: HIV (Stage A2: VL 10,000 and CD4+ 390)
• April 2006:
• HAART (VL 8,000 and CD4+ 199) with TDF+FTC+LPV/r • Chronic HBV (VL out of range; AST 50, ALT 82)
• Oct 2006
– HIV: VL <50 and CD4+ 527 – HBV: VL undetectable and normal liver enzymes
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Social history
• Difficulty concentrating and lack of attention since early childhood: Mild intellectual disability (1987)
• Single MSM
• Works as a hair dresser
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Current History
• During follow-up, in a routine analysis the patient presented hypophosphatemia and glucosuria
• Patient was asymptomatic
• No clinical, immunologic or viral failure was documented
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Lab results
Blood chemistry
• Glucose 88 mg/dl
• Na+ 141 mEq/L
• K+ 3,8 mEq/L
• Ca2+ 9,4 mg/dl
• P- 2,24 mg/dl
• Urea 15 mg/dl
• Creatinine 1,02 mg/dl
• CrCl 103 ml/min/1.73m2
Urine
• Glucose 100 mg/dL
• Protein (-)
• WBC < 5
• RBC (-)
• No casts
CBC: within normal range
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Clinical Problem
34 y/o male co-infected (HIV-HBV) patient with renal glucosuria and hypophosphatemia, 6 months after initiation of HAART (TDF+FTC+LPV/r)
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What test would you do?
Renal glucosuria
“Renal glucosuria can be caused primarily either by mutations in the Na+-glucose transporter in the proximal tubulus or by tubular damage”
Siegenthaler’s Differentila Diagnosis in Internal Medicine. From Symptom to Diagnosis . First English edition, 2007.
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Is there a tubular disorder?
Siegenthaler’s Differentila Diagnosis in Internal Medicine. From Symptom to Diagnosis . First English edition, 2007.
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What test would you do?
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Urinary electrolytes, proteins and amino acids
• Alpha-1-microglobulin: 34mg/24hr
• Beta-2-microglobulin: 3mg/24hr
• Phosphate: 951 mg/24h
• Fraction of phosphate excretion: 32,56%
• Glucosuria
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Causes of tubular dysfunction
Inhereted
• Cystinosis
• Wilson disease
• Hereditary tyrosinemia
• Lowe syndrome (oculocerebrorenal osteodystrophy)
Acquired
• Pyelonephritis
• Fanconi-de Toni-Debre syndrome
• Multiple Myeloma
Siegenthaler’s Differentila Diagnosis in Internal Medicine. From Symptom to Diagnosis . First English edition, 2007.
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Causes of tubular dysfunction
Inhereted
• Cystinosis
• Wilson disease
• Hereditary tyrosinemia
• Lowe syndrome (oculocerebrorenal osteodystrophy)
Acquired
• Pyelonephritis
• Fanconi-de Toni-Debre syndrome
• Multiple Myeloma
Siegenthaler’s Differentila Diagnosis in Internal Medicine. From Symptom to Diagnosis . First English edition, 2007.
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Fanconi syndrome…HIV+ on HAART
• Dysproteinemias (MM, Amyloidosis)
• Heavy metals (cadmium, lead, mercury, platinum, and uranium)
• Pharmacologic: TDF, ADV, valproic acid, aminoglycosides, tetracycline
American Journal of Kidney Diseases, 2011-05-01
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TDF induced Fanconi
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However…
• NO increase in Cr or decrease in CrCl
• NO aminoaciduria
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Social history
• Difficulty concentrating and lack of attention since early childhood: Mild intellectual disability (1987)
• Single MSM
• Works as a hair dresser
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Clinical Problem
34 y/o male with mild cognitive impairment, co-infected (HIV-HBV) patient on HAART (TDF+FTC+LPV/r) with renal tubular dysfunction and hyperphenylalanuria
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Hyperphenylalanuria? Serum Phe Hyperphenylalanemia
• Phenylketonuria (PKU)
• Tetrahydrobiopterin (BH4) deficiency
• Tyrosinemia
Zelikovic I. Aminoaciduria and glycosuria. In: Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology. 4th ed. Lippincott Williams & Wilkins; 1999:507-27.
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Hyperphenylalanuria? Serum Phe Hyperphenylalanemia
• Phenylketonuria (PKU)
• Tetrahydrobiopterin (BH4) deficiency
• Tyrosinemia
Zelikovic I. Aminoaciduria and glycosuria. In: Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology. 4th ed. Lippincott Williams & Wilkins; 1999:507-27.
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Other tests
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What test would confirm the diagnosis?
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Diagnosis
1. TDF induced renal tubular dysfunction
2. Moderate form of PKU
3. Chronic HBV
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How should this patient be managed?
1. PKU
2. TDF induced tubular dysfunction
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1. PKU: A quick review
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Overview
• Most common inborn error of amino acid metabolism
• Autosomal recessive
• Mutations in the PAH gene 12q24.1 (98%)
• > 500 different mutations have been identified
Blau N. Phenylketonuria and BH4 Deficiencies. First edition. UNI-MED Verlag, Bremen 2010.
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Where’s the defect?
Blau N. Phenylketonuria and BH4 Deficiencies. First edition. UNI-MED Verlag, Bremen 2010.
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Mode of inheritance
Blau N. Phenylketonuria and BH4 Deficiencies. First edition. UNI-MED Verlag, Bremen 2010.
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Clinical manifestations • Musty odor
• Intellectual disability (most common)
• Fair skin and hair
• Eczema
• Sclerodermalike plaques
• Epilepsy (50%) and extrapyramidal manifestations
Sanjurjo P, Baldellou A. Diagnóstico y tratamiento de las enfermedades metabólicas hereditarias. T Tercera edición. Editorial Ergon, Madrid 2010.
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Diagnosis and Classification
• Screening (TMS / Guthrie test)
• Serum phenylalanine (Phe) > 240 µmol/L
– Mild 240-600 µmol/L
– Moderate 600-1,200 µmol/L
– Classic PKU > 1,200 µmol/L
Sanjurjo P, Baldellou A. Diagnóstico y tratamiento de las enfermedades metabólicas hereditarias. T Tercera edición. Editorial Ergon, Madrid 2010.
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Treatment • Muldisciplinary approach
• Low Phe diet
• Dietary supplements (LNAA, Folinic acid)
• Tetrahydrobiopterin (SAPROPTERIN)
– BH4-responsive PKU > 4 y/o
– All patients with BH4 deficiency
1) Blau N. Phenylketonuria and BH4 Deficiencies. First edition. UNI-MED Verlag, Bremen 2010. 2) Sanjurjo P, Baldellou A. Diagnóstico y tratamiento de las enfermedades metabólicas hereditarias. T
Tercera edición. Editorial Ergon, Madrid 2010.
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How should this patient be managed?
1. PKU
2. TDF induced tubular dysfunction
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2. TDF induced tubular dysfunction
Would you change HAART? HIV/HBV+ patient
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Our management
• TDF was stopped
– Tubular dysfunction subsided
• 3TC was initiated and LPV/r maintained
• HBV: VL remains undetectable
– LFT in normal range
– Fibroscan: Kpa 5,4 (F0-F1)
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