Clinical case: 17-04-2012
Carlos Mejía Chew
MIR 2
34 Y/O MALE HIV+ PATIENT WITH HYPOPHOSPHATEMIA
AND GLUCOSURIA
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
Social history
• Difficulty concentrating and lack of attention since early childhood: Mild intellectual disability (1987)
• Single MSM
• Works as a hair dresser
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
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
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)
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.
Is there a tubular disorder?
Siegenthaler’s Differentila Diagnosis in Internal Medicine. From Symptom to Diagnosis . First English edition, 2007.
What test would you do?
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
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.
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.
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
TDF induced Fanconi
However…
• NO increase in Cr or decrease in CrCl
• NO aminoaciduria
Social history
• Difficulty concentrating and lack of attention since early childhood: Mild intellectual disability (1987)
• Single MSM
• Works as a hair dresser
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
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.
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.
Other tests
What test would confirm the diagnosis?
Diagnosis
1. TDF induced renal tubular dysfunction
2. Moderate form of PKU
3. Chronic HBV
How should this patient be managed?
1. PKU
2. TDF induced tubular dysfunction
1. PKU: A quick review
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.
Where’s the defect?
Blau N. Phenylketonuria and BH4 Deficiencies. First edition. UNI-MED Verlag, Bremen 2010.
Mode of inheritance
Blau N. Phenylketonuria and BH4 Deficiencies. First edition. UNI-MED Verlag, Bremen 2010.
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.
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.
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.
How should this patient be managed?
1. PKU
2. TDF induced tubular dysfunction
2. TDF induced tubular dysfunction
Would you change HAART? HIV/HBV+ patient
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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