Clinical case - Lowe syndrome
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Transcript of Clinical case - Lowe syndrome
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Clinical Case Study
By:Dr. Tikal Kansara
R3 Medicine D Unit
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HISTORY OF CURRENT ILLNESS
• Fever for 3 days– High grade, with chills & rigors
• Vomiting for 3 days• Headache for 3 days– Severe, global, throbbing type
• Convulsions for 2 days– GTC type, total of 3 episodes
• Pain in left lower limb around hip for 2 days– After convulsions
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PAST HISTORY
• Dimness of vision since age of 4 years– Progressive, improved after bilateral cataract surgery at
the age of 6 years• Recurrent episodes of convulsions since the age of
10 years– 1 – 2 episodes in a few months
• Headache since the age of 10 years – Intermittent episodes, each lasting a few hours to a day
or two– Frequency once in 15 to 20 days
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• Generalized weakness & bodyache since the age of 10 years– Mild aches to begin with; progressed to an extent
that he was unable to cycle to school, so he left school
• Swelling on the outer side of right thigh 1 year ago– Painful, throbbing type– Relieved after Incision and Drainage– Left a 3 x 4 cm scar on right side of thigh
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INTRAUTERINE HISTORY– No maternal history of any major medical illness during pregnancy. ANC and
Inj. TT regularly takenBIRTH HISTORY
– SFD – FTND. On some oral syrups for the sameDEVELOPMENTAL HISTORY
– All developmental milestones are not available but he started walking at 15 – 16 months age
– He was always the shortest in height in his schoolIMMUNISATION HISTORY
– All immunizations were takenFAMILY HISTORY
– Patient has no siblings– Cousin (maternal) is short statured
TREATMENT HISTORY– Had cataract surgery done at age of 6 years– Patient did not seek any medical attention for his convulsions
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HISTORY CONCLUSIONSo, at the end of history of current illness, we have a 16 year old boy with acute onset of fever, vomiting, headache and convulsions with sequel of left lower limb pain; most likely we are dealing with a case of:• Acute Meningoencephalitis • Cerebral Malaria• Acute febrile illness reducing the seizure threshold
In a background of bilateral progressive cataracts, convulsions, generalised debilitating bodyache for nearly a quarter of decade, in a short stature child (s/o – failure to thrive) without auditory symptoms or symptoms of dyspnoea, squatting episodes or urinary disturbances (hematuria, polyuria, burning micturation); we are prompted to believe him as a part of syndrome, most likely being:• Hypoparathyroidism (eg. Familial, isolated)• Galactosemia (Classical)• Down Syndrome
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• Hairs – Normal• Facial Features – Symmetrical• Teeth and Palate – Normal• Extremities – Normal• Palms and Soles – Normal• Pallor present
GENERAL EXAMINATION
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MOTOR FUNCTIONS
• Nutrition:– Wasting present; but bilaterally symmetrical
• Tone:– Upper limb:
• Right: Reduced• Left: Reduced
– Lower limb:• Right: Reduced• Left: Not elicited
• Power– 4/5 in both upper limbs & right lower limb
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REFLEX RIGHT LEFT
Biceps Jerk - -
Triceps Jerk - -
Supinator Jerk - -
Knee Jerk - -
Ankle Jerk - -
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Ophthalmology Examiation
Pseudophakia with PCO (Posterior Capsular Opacity) present. Fundus not properly visualised.
Vision: FC 6 – 8 Feet on bedside. Further not possible
Stain: Negative
Tension:Right eye: 17.3 mmHg (Normal)Left Eye: 17.3 mmHg (Normal)
No abnormal eye movementsNormal ocular positionIntraocular pressure is normal
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HISTORY & PE CONCLUSIONSo, at the end of history & PE, we have a 16 year old boy with acute onset of fever, vomiting, headache and convulsions with sequel of left lower limb pain; with tachypnea, tachycardia without signs of meningeal irritation;
In a background of bilateral progressive cataracts, convulsions, generalised debilitating bodyache for nearly a quarter of decade, in a short stature child (s/o – failure to thrive) without auditory symptoms or symptoms of dyspnoea, squatting episodes or urinary disturbances (hematuria, polyuria, burning micturation); with wasting, generalised hypotonia & areflexia we are prompted to believe him as a part of syndrome, most likely being:
• Hypoparathyroidism (Familial, isolated)• Galactosemia (Classical)• Fanconi Syndrome
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INVESTIGATIONS
09 / 06 10 / 06 Normal ValuesHemoglobin 5.1 5.30 14 – 17 gm%Total WBC 7300 / cmm 5,800 / cmm 4000 – 11000 /cmmDifferentials 60 / 34 / 4 / 2 68 / 30 / 01 / 01Platelets 232000 Adequate 150000 – 45000 / cmmSmear Hypochromia + Mild Microcytic
Hypochromic RBCsFew Elliptocytes
Malarial Parasite Not detected Not detected
ESR 40
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09 / 06 10 / 06 Normal ValuesUrea 113 mg/dl 115 mg/dl 14 – 40 mg/dlCreatinine 12.6 mg/dl 14.16 mg/dl M: 0.7 – 1.4 mg/dlBilirubin (T) 0.6 mg/dl 0.1 – 0.2 mg/dlBilirubin (D) 0.2 mg/dl 0 – 0.4 mg/dlBilirubin (ID) 0.4 mg/dl 0.1 – 0.8 mg/dl
BIOCHEMICAL INVESTIGATION
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09 / 06 10 / 06 12 / 06 Normal ValuesS. Na 134 135 – 145 mEq/LS. K 3.2 2.7 3.5 – 5.5 mEq/LS. Calcium (T) 8.7 7.9 8.4 – 10.3 mg/dlS. Calcium (I) 0.9 1.1 – 1.35 mmol/LS. Phosphorus 5.5 2.6 – 4.5 mg/dlS. Magnesium 2.6 M: 1.8 – 2.6 mg/dlS. Chloride 114 98 – 107 mmol/L
SERUM ELECTROLYTES
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URINE REPORT (11 / 06 / 2016)
Color Yellow
Appearance Slightly turbid
Reaction (pH) 6.0
Specific Gravity 1.020
Chemical Examination
Urine Albumin Present (++)
Urine Sugar (Qualitative) Present (+)
Ketones Absent
Microscopic Examination
Pus cells / hpf 2 – 3 / hpf
RBC / hpf 2 – 5 / hpf
Epithelial cells / hpf Occassional / hpf
Casts / lpf Absent
Crystals Absent
Yeast / Fungus Absent
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Widal Test (08 / 06)
S. Typhi “O” 1 : 120
S. Typhi “H” 1 : 60
10 / 06 Normal Values
S. Protein 7.2 6.0 – 8.0 gm/dl
S. Albumin 3.4 3.2 – 5.0 gm/dl
S. Globulin 3.8
ECG Normal
RBS 122 mg / dL
TSH 0.62 (Normal Range: 0.27 – 4.20 µIU/ml)
Viral Markers
HIV Negative
HbsAg Negative
HCV Negative
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Liver:Size: NormalEchopattern: NormalNo dilated IHBR/Focal lesionPV at porta: Normal CBD: Normal
Pancreas: Size: Normal; Normal echopattern, no focal lesion
Spleen: Size 8.9 cm normal. Normal echopattern, no focal lesionRight Kidney:
Size 6.6 x 2.1 cmShows mild hydronephrosisNo e/o calculus noted
Left Kidney:Size: 5.4 x 2.2 cmNo e/o calculus/hydronephrosis noted
Bilateral kidneys appear small in size with loss of cortico-medullary differenciation
IMPRESSION:Changes of chronic renal parenchymal disease
ULTRASOUND ABDOMEN
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CEREBROSPINAL FLUID EXAMINATIONCEREBROSPINAL FLUID EXAMINATIONPhysical Examination
Amount 1 mlColour ColourlessAppearance Slightly turbidBlood Absent
Biochemical ExaminationProtein 120 mg/dlSugar 96 mg/dlADA level 0.39 U/L
Microscopic ExaminationTotal Count 70 cells/mlTotal RBCs Rare cells/mlDifferential 75 / 25
Microscopic ExaminationGram & Zn stain No organism detected
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MRI BRAIN – PLAIN + CONTRAST
• No significant diagnostic intracranial abnormality detected
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X-Rays• X-Ray PBH:– Reduced bone density
noted involving visualized bones with # neck left femur with upward displacement of shaft of left femur
– Bilateral hip joint space appears preserved
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• X-Ray B/L knee (AP & Lateral):– Reduced density of
visualized bones noted with dense sclerosis of the metaphysis of the bones (Tibia & Fibula)
– B/L knee joint space is preserved
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• CXR - PA
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13 / 06 14 / 06pH 7.30 7.15P CO2 20.6 mmHg 26.0 mmHgP O2 64 mmHg 52 mmHgOxygen Saturation 90.6 % 76.8 %cHCO3 9.9 mmol/L 8.6 mmol/L
ARTERIAL BLOOD GAS ANALYSIS
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Hospital Course
09 / 06 10 / 06 11 / 06 12 / 06 13 / 06 14 / 06 14 / 06
Creatinine 12.6 14.16 9.03 5.46 3.65 3.49 3.79
HD 1 HD 2 HD 3
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13 / 06 14 / 06
pH 7.30 7.15
P CO2 20.6 mmHg 26.0 mmHg
P O2 64 mmHg 52 mmHg
Oxygen Saturation 90.6 % 76.8 %
cHCO3 9.9 mmol/L 8.6 mmol/L
Underlying metabolic acidosis
Bicarbonate supplementation added to prescription
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Interpretation of Investigations
• Anion Gap = (Na + K) – (Cl + HCO3) = (134 + 3.2) – (114 + 9.9)
= 13.3 (Normal)• Hypokalemia
• Hyperchloremia• Metabolic acidosis worsened in spite of HCO3 supplementation
09 / 06 10 / 06 12 / 06 13 / 06 15 / 06S. K 3.2 2.7 3.4 3.3
13 / 06 14 / 06pH 7.30 7.15cHCO3 9.9 mmol/L 8.6 mmol/L
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• So, we have a hyperchoremic metabolic acidosis with hypokalemia, without evidence of renal stones (No symptoms & USG not s/o stones), which worsens in spite of bicarbonate supplementation
• These features are s/o Type II (Proximal) Renal Tubular Acidosis
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TYPE 1 DISTAL RTA TYPE 2 PROXIMAL RTA TYPE 4 RTA
DefectReduced H+ excretion in distal tubule
Impaired HCO3 reabsorption in proximal tubule
Impaired cation exchange in distal tubule
Hyperchloremic Normal anion gap metabolic acidosis
Yes Yes Yes
Minimum urine pH
> 5.5 (always) < 5.5 (ill – defined) < 5.5
Plasma HCO3 < 15 Usually >15 Usually > 15
Plasma K Low-normal Low-normal High (always)Renal Stones Almost always present No No
Causes
Hereditary - Band 3 mutation (association with sensorineural deafness)
Aquired – Autoimmune (eg Sjogren), cirrhosis, sickle cell anaemia, renal transplantation
Hereditary – Cystinosis, Wilson dz, galactosemia, fructose intolerance, etc
Aquired – Amyloidosis, Multiple Myeloma, Paroxysmal Nocturnal Hemoglobinuria, HAART
Disorders of renal interstitum and tubules with GFR > 20 mL/min
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• In addition to this, the patient has features of reduced bone mineral density on X-Rays (Osteomalacia >> Renal Osteodystrophy)– With pathological # following convulsions (a trivial
trauma)• Proteinuria• Glucosuria• Failure to thrive & anaemia
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• So, combining the two ,we have– Hyperchloremic– Metabolic acidosis– Hypokalemia– Radiological features of reduced bone density severe
enoughfor pathological # of long bone (left femur) (s/o long standing loss of calcium & phosphorus in urine)
– Proteinuria– Glucosuria– Failure to thrive
• These features comprise - Fanconi Syndrome
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Favours Fanconi Syndrome in our patient Against Fanconi Syndrome in our patient
Metabolic Acidosis <<None>>
Hypokalemia <<None>>
Hyperchloremia <<None>>
Proteinuria (Mild) as no edema in the patient during the last decade & normal serum albumin
<<None>>
Glucosuria <<None>>
Failure to thrive <<None>>
After advanced medicorenal disease sets in, amino acids may not be found in urine. But wasting was present, s/o reduced muscle mass
Did not perform urinary loss of amino acids
Already an advanced medicorenal disease with shrunken kidney has set in.Features on X-Ray & anthropometry are have features of chronically reduced phosphorus & calcium
Hyperphosphatemia
Did not demonstrate phosphaturia
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Fanconi Syndrome
• Inherited –– Cystinosis, Wilson disease, Lowe Syndrome,
Galactosemia, Glycogen storage disease, Hereditary Fructose Intolerance
• Aquired – – Outdated Tetracyclines, Tenofovir & didanosine,
Multiple Myeloma and monoclonal gammopathy
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Combining everything available !!!• Fanconi Syndrome• Bilateral cataracts (operated); with resurrgence of
posterior capsular opacity• Long history of convulsions (without any structural
lesions in brain) & hypotonia with areflexia on examination
Oculo Cerebro RenalSyndrome
LOWE SYNDROME
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Lowe Syndrome
• X-linked recessive syndrome• Incidence 1:200,000 to 1:500,000• Congenital cataracts, hypotonia and areflexia,
proximal tubular acidosis, aminoaciduria, phosphaturia and low molecular weight proteinuria with intellectual disability
• Diagnosed by inositol polyphosphate 5-phosphatase enzyme activity in cultured skin fibroblasts and by OCRL1 gene study
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