Refractory rickets due to Fanconi's Syndrome secondary to Wilson's disease
A 13-year-old girl, first-born of a nonconsanguineous marriage, with normal perinatal history and developmental milestones, presented with complaints of an insidious onset of progressive weakness involving both lower limbs, in the form of a difficulty in getting up from a squatting position since six years. She also noticed pain in her hips and lower limbs with a gradual development of knock-knees over the same period of time. She had pain and discomfort in her elbow and knees joints. Her dietary intake included about 450 mL of milk per day. Sun exposure was adequate. She had received multiple cycles of vitamin D sachets over the six-year period with minimal improvement. There was no history of tingling around the mouth or the fingertips and no history of polyuria, swelling of lower limbs, jaundice, persistent diarrhea, or intake of drugs. There was also no history of similar complaints among the family members.\nExamination revealed an oriented, alert, poorly built, poorly nourished child (weight: 18.6 kg, <3rd percentile) with a severely short stature [height: 120 cm <3rd percentile, standard deviation score (SDS): -5.43, target height: 146 cm, SDS: -2.48], mildly pale, nonicteric, and stable vitals. Examination of musculoskeletal system revealed widening and tenderness of wrists with valgus deformity at knees []. Examination of the central nervous system revealed normal mental functions, cranial nerve, and sensory system. Examination of the motor system showed normal tone and a power of 4/5 in the muscle groups in all the limbs with normal reflexes. The patient also had a palpable liver with a span of 11 cm, and no nodularity or tenderness. No palpable spleen or shifting dullness was noted.\nBiochemical evaluation revealed mild microcytic hypochromic anemia, normal renal functions, normal transaminases, low albumin, hypokalemia, elevated bone-specific alkaline phosphatase, normal corrected calcium, hypophospatemia, and adequate levels of 25-hydroxyvitamin D []. Twenty-four-hour urine levels of phosphate and creatinine were 0.29 g and 277 mg, respectively. Tubular maximum reabsorption of phosphate per unit of glomerular filtrate (TmP/GFR) was low at 1.4 mg/dL, indicating a renal loss of phosphate. Arterial blood gas analysis revealed normal anion gap metabolic acidosis with a urine pH of 7. Skeletal radiography revealed epiphyseal dysgenesis with a loss of horizontal trabeculations at both femoral necks, pseudofractures around the knees, and widening of epiphysis of both knees and wrists []. Ammonium chloride challenge test done to check the ability to acidify urine was positive, suggesting proximal tubular dysfunction []. On further testing, she was found to have glucosuria in the presence of normal blood sugars and also aminoaciduria, thus suggesting a diagnosis of Fanconi's syndrome. To screen for causes of Fanconi's syndrome, a slit-lamp examination was done and it revealed the presence of Kayser-Fleischer rings which prompted an evaluation for Wilson's disease []. Serum ceruloplasmin levels were low and 24-hour urine copper levels were high []. A detailed examination of the central nervous system revealed spastic dysarthria. Ultrasonography of the abdomen showed a normal-sized liver with coarse architecture; portal vein, spleen, and kidneys were normal. Prothrombin time and upper gastrointestinal endoscopy were normal. Magnetic resonance (MR) imaging of the brain showed bilateral symmetrical hyperintensities in T2-weighted images in the basal ganglia, midbrain, periaqueductal areas, cerebellum, and the frontal lobes consistent with Wilson's disease. Thus a diagnosis of short stature and refractory rickets due to Fanconi's syndrome secondary to Wilson's disease was made. She was started on a replacement of potassium and alkali in the form of potassium Shohl's solution 20 mL thrice a day (t.i.d) and replacement of phosphate with Joule's solution along with a replacement of calcium and vitamin D. Wilson's disease was treated with zinc acetate tablets 50 mg three times a day.