This clinical case study describes a 16-year-old boy presenting with fever, vomiting, headache, and convulsions. His past medical history is significant for bilateral cataracts, recurrent convulsions since age 10, headaches, weakness, and reduced growth. Physical exam reveals wasting, hypotonia, areflexia, and pseudophakia. Investigations show features of Fanconi syndrome including metabolic acidosis, hypokalemia, hyperchloremia, proteinuria, and glucosuria. Radiographs show reduced bone density. The constellation of findings are consistent with Lowe syndrome, a rare X-linked condition causing Fanconi syndrome, cataracts, and neurological impairment.

1. Clinical Case Study
By:
Dr. Tikal Kansara
R3 Medicine D Unit

2. 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

3. 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

4. • 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

5. INTRAUTERINE HISTORY
– No maternal history of any major medical illness during pregnancy.
ANC and Inj. TT regularly taken
BIRTH HISTORY
– SFD – FTND. On some oral syrups for the same
DEVELOPMENTAL 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 school
IMMUNISATION HISTORY
– All immunizations were taken
FAMILY 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

6. HISTORY CONCLUSION
So, 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

7. • Hairs – Normal
• Facial Features – Symmetrical
• Teeth and Palate – Normal
• Extremities – Normal
• Palms and Soles – Normal
• Pallor present
GENERAL EXAMINATION

8. 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

9. REFLEX RIGHT LEFT
Biceps Jerk - -
Triceps Jerk - -
Supinator Jerk - -
Knee Jerk - -
Ankle Jerk - -

10. 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 movements
Normal ocular position
Intraocular pressure is normal

11. HISTORY & PE CONCLUSION
So, 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

12. INVESTIGATIONS
09 / 06 10 / 06 Normal Values
Hemoglobin 5.1 5.30 14 – 17 gm%
Total WBC 7300 / cmm 5,800 / cmm 4000 – 11000 /cmm
Differentials 60 / 34 / 4 / 2 68 / 30 / 01 / 01
Platelets 232000 Adequate 150000 – 45000 / cmm
Smear Hypochromia + Mild Microcytic
Hypochromic RBCs
Few Elliptocytes
Malarial Parasite Not detected Not detected
ESR 40

13. 09 / 06 10 / 06 Normal Values
Urea 113 mg/dl 115 mg/dl 14 – 40 mg/dl
Creatinine 12.6 mg/dl 14.16 mg/dl M: 0.7 – 1.4 mg/dl
Bilirubin (T) 0.6 mg/dl 0.1 – 0.2 mg/dl
Bilirubin (D) 0.2 mg/dl 0 – 0.4 mg/dl
Bilirubin (ID) 0.4 mg/dl 0.1 – 0.8 mg/dl
BIOCHEMICAL INVESTIGATION

14. 09 / 06 10 / 06 12 / 06 Normal Values
S. Na 134 135 – 145 mEq/L
S. K 3.2 2.7 3.5 – 5.5 mEq/L
S. Calcium (T) 8.7 7.9 8.4 – 10.3 mg/dl
S. Calcium (I) 0.9 1.1 – 1.35 mmol/L
S. Phosphorus 5.5 2.6 – 4.5 mg/dl
S. Magnesium 2.6 M: 1.8 – 2.6 mg/dl
S. Chloride 114 98 – 107 mmol/L
SERUM ELECTROLYTES

15. 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

16. 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

17. Liver:
Size: Normal
Echopattern: Normal
No dilated IHBR/Focal lesion
PV at porta: Normal CBD: Normal
Pancreas:
Size: Normal; Normal echopattern, no focal lesion
Spleen: Size 8.9 cm normal. Normal echopattern, no focal lesion
Right Kidney:
Size 6.6 x 2.1 cm
Shows mild hydronephrosis
No e/o calculus noted
Left Kidney:
Size: 5.4 x 2.2 cm
No 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

18. CEREBROSPINAL FLUID EXAMINATIONCEREBROSPINAL FLUID EXAMINATION
Physical Examination
Amount 1 ml
Colour Colourless
Appearance Slightly turbid
Blood Absent
Biochemical Examination
Protein 120 mg/dl
Sugar 96 mg/dl
ADA level 0.39 U/L
Microscopic Examination
Total Count 70 cells/ml
Total RBCs Rare cells/ml
Differential 75 / 25
Microscopic Examination
Gram & Zn stain No organism detected

19. MRI BRAIN – PLAIN + CONTRAST
• No significant diagnostic intracranial
abnormality detected

20. 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

21. • 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

22. • CXR - PA

23. 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
ARTERIAL BLOOD GAS ANALYSIS

24. 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

25. 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

26. 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 / 06
S. K 3.2 2.7 3.4 3.3
13 / 06 14 / 06
pH 7.30 7.15
cHCO3 9.9 mmol/L 8.6 mmol/L

27. • 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

28. TYPE 1 DISTAL RTA TYPE 2 PROXIMAL RTA TYPE 4 RTA
Defect
Reduced 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

29. • 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

30. • 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

31. 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

32. 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

33. 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

34. 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