A 20-year-old female, born out of a non-consanguinous marriage, with no significant family history, presented with complaints of 3-year long progressive low back pain, bilateral hip and shoulder pain, that gradually worsened, resulting in difficulty in walking and performing activities of daily living. This was not associated with proximal muscle weakness, early morning stiffness, or increased urinary frequency. There was no history of trauma, long-term drug use like steroids or antiepileptics, or chronic systemic illness. On examination, she was conscious and oriented, with preserved higher mental functions. Neurological examination revealed proximal muscle weakness (power 3/5 in lower limbs) with intact reflexes and sensation. Diffuse bony tenderness was noted, particularly over the pelvic girdle and lumbar spine. Antalgic gait was noted. Radiological Imaging done by CT Hip showed diffuse osteoporotic changes in the Dorso-lumbar vertebrae, pelvic bones, and femur (Figure 2). Pathological Undisplaced fracture noted in Right Ala of Sacrum (Figure 1) Figure 1 – Arrow mark depicting Right Sacral Ala Fracture Line Figure 2 – Diffuse Osteoporotic Changes across Dorsolumbar Vertebra and Pelvic bones Dual-energy X-ray absorptiometry (DXA) demonstrated Severe osteoporosis with markedly reduced bone mineral density. Ultrasound of the abdomen showed normal-sized kidneys with normal echoes. Table 1: Depicts the Blood investigations done through the course of her hospital stay Parameter Result Units Reference Range Interpretation Serum Biochemistry Calcium 8.7–10.3 mg/dL 8.6–10.4 Normal Phosphorus 0.8–1.5 mg/dL 2.5–4.5 Low Sodium 137 mEq/L 136–146 Normal Potassium 3.5 mEq/L 3.5–5.0 Low-normal Chloride 109 mEq/L 98–110 Normal Creatinine 0.8 mg/dL 0.5-1.3 mg/dL Normal eGFR 108 mL/min/1.73m2 Normal Albumin 4.3–4.8 g/dL 3.5–5.0 Normal Total Protein 6.6 g/dL 6.5–8.0 Normal ALP 201–213 IU/L 35–130 Mildly elevated AST 20 IU/L 12–38 Normal ALT 13 IU/L 7–41 Normal Acid–Base Status Arterial pH 7.28 – 7.35–7.45 Low HCO₃⁻ 20.2 mmol/L 22–26 Low Anion Gap Normal – 8–12 Normal Urine pH 6.0–6.5 – 5.5–7.0 Inappropriately high Urine Findings Glucose 2+ – Negative Renal glucosuria Protein 2+ – Negative Tubular proteinuria Leukocytes - – Negative – Blood 1+ – Negative – Specific Gravity 1.020 – 1.015–1.025 Normal Microprotein 183 mg/dL – Elevated UPCR 3.38 – <0.20 Elevated Urine Sodium 124 mEq/L – – Urine Potassium 23.9 mEq/L – – Urine Creatinine 54.1 mg/dL - Elevated Phosphate Handling Urine Phosphate 13.7 – – Renal phosphate wasting Tubular Reabsorption of Phosphate 0.584 – >0.85 Reduced Ca/Cr Ratio 0.5 – <0.2 Elevated Endocrine Evaluation PTH 23 pg/mL 16–65 Normal Vitamin D (25-OH) 5.48 ng/mL 30–80 Severely low TSH 1.86 µIU/mL 0.3–4.2 Normal Free T4 1.16 ng/dL 0.93–1.7 Normal Free T3 5.6 pmol/L 3.1–6.8 Normal Intact FGF23 8.55 pg/mL 23–95 Low Given her young age and progressive musculoskeletal symptoms, secondary causes of osteoporosis were evaluated. MRI Lumbar Spine showed no evidence of compressive or intrinsic cord pathology. Hematological parameters, renal function, calcium levels, and imaging findings were not suggestive of plasma cell dyscrasia. Inflammatory markers were normal, and there were no clinical features of rheumatologic disease. There was no history of drug exposure or toxin intake. Although vitamin D deficiency was present, the associated hypophosphatemia, metabolic acidosis, normoglycemic glycosuria, proteinuria, and aminoaciduria suggested a proximal tubular defect, a Fanconi – like syndrome rather than isolated nutritional deficiency. Genetic analysis was done, which confirmed the presence of a mutation in the SLC34A1 gene locus on Chromosome 5q. This confirmed our diagnosis of Fanconi Renotubular Syndrome 2. Her parents and her sister subsequently tested negative for Fanconi’s syndrome with a urinary amino acid screen. The patient was managed with oral sodium bicarbonate and oral potassium citrate. Vitamin D and oral Phosphorus supplementation was given. Her stress fracture was managed conservatively, and the patient was followed up at regular intervals. After 3 months and 6 months of follow-up, her pain has significantly subsided, and she has resumed her regular daily activities with ease. Serum Calcium, Phosphorus, and Bicarbonate were maintained within normal limits.

Fanconi Renotubular Syndrome 2 is a rare inherited proximal tubular disorder characterized by impaired reabsorption of phosphate and other solutes in the proximal tubule, leading to phosphaturia, glycosuria with normoglycemia, aminoaciduria, and varying degrees of metabolic acidosis. Mutations in the SLC34A1 gene, located on chromosome 5q, encode the sodium–phosphate cotransporter (NaPi-IIa), a key transporter responsible for renal phosphate reabsorption.[2] Dysfunction of this transporter results in chronic phosphate wasting, defective bone mineralization, and subsequent osteomalacia or severe osteoporosis, particularly in young individuals.[3] Our patient presented with progressive musculoskeletal pain, pathological sacral fracture, and severe osteoporosis at the age of 20 years, an age at which primary osteoporosis is uncommon. The chronicity of symptoms, absence of trauma, and lack of systemic inflammatory features prompted consideration of a broad differential diagnosis. Neurological causes such as compressive myelopathy were ruled out by a normal MRI spine. Plasma cell dyscrasia was unlikely given normal hemogram, renal function, calcium levels, and absence of lytic lesions. Inflammatory myopathy and rheumatological disorders were excluded based on clinical and laboratory parameters. Although vitamin D deficiency was present, it could not account for the constellation of severe hypophosphatemia, euglycemic glycosuria, aminoaciduria, proteinuria, and metabolic acidosis. The presence of these findings with preserved renal function strongly suggested a generalized proximal tubular defect, consistent with a Fanconi-like syndrome.[4] Unlike acquired forms of Fanconi syndrome—which are commonly secondary to drugs (e.g., tenofovir, ifosfamide), heavy metal toxicity, or systemic diseases—our patient had no relevant exposure history, making an inherited etiology more likely. Genetic confirmation of an SLC34A1 mutation established the diagnosis of Fanconi Renotubular Syndrome 2. This condition may demonstrate variable phenotypic expression, ranging from nephrolithiasis and hypercalciuria to hypophosphatemic rickets or osteomalacia.[5] Interestingly, despite being born to a non-consanguineous marriage and having no significant family history, the patient manifested clinically significant disease in early adulthood. Negative screening of her parents and sibling suggests either a de novo mutation or a recessive inheritance with carrier status not detected on urinary screening alone.[6] The pathophysiology of skeletal involvement in this disorder is primarily driven by chronic phosphate depletion. Phosphate is essential for hydroxyapatite formation and bone mineralization; persistent losses result in defective mineralization, bone pain, fractures, and proximal muscle weakness[7]. The pathological sacral fracture observed in our patient likely represents an insufficiency fracture secondary to prolonged osteomalacia. Management of proximal tubular disorders is largely supportive and aimed at correcting metabolic derangements. Alkali therapy with sodium bicarbonate and potassium citrate corrects metabolic acidosis, thereby improving bone buffering and reducing further mineral loss. Phosphate supplementation and vitamin D replacement address hypophosphatemia and improve mineralization.[8][9] Our patient demonstrated significant symptomatic improvement within six months of therapy, along with normalization of serum calcium, phosphate, and bicarbonate levels, underscoring the importance of early recognition and targeted metabolic correction.

This case highlights several important clinical lessons. First, severe osteoporosis or pathological fractures in young adults should prompt evaluation for secondary causes, particularly renal tubular disorders. Second, the presence of hypophosphatemia with euglycemic glycosuria and normal renal function is a key diagnostic clue toward proximal tubular dysfunction. Finally, genetic confirmation not only establishes the diagnosis but also aids in counseling and prognostication.[10] In conclusion, this case emphasizes the need for high clinical suspicion for inherited proximal tubular disorders in young patients presenting with unexplained osteoporosis and fractures. Early diagnosis and metabolic correction can significantly improve functional outcomes and prevent long-term skeletal morbidity.

1. Foreman JW. Fanconi Syndrome. Pediatr Clin North Am. 2019 Feb;66(1):159-167. doi: 10.1016/j.pcl.2018.09.002. PMID: 30454741. 2. Lee JH, Byun YS, Cha BS, Nam MS, Song YD, Lim SK, et al. A case of adult fanconi syndrome with hypophosphatemic osteomalacia. Endocrinol Metab 1996;11:93-101. Doi: 10.1159/000188827 3. Rao M, Dadey L, Glowa T, Veldkamp P. Fanconi Syndrome Leading to Hypophosphatemic Osteomalacia Related to Tenofovir Use. Infect Dis Rep. 2021 May 24;13(2):448-453. doi: 10.3390/idr13020044. PMID: 34073672; PMCID: PMC8162330. 4. Gupta S, Kamat N, Shenoy DV, Agarwal S. Adult-Onset Fanconi Syndrome Presenting as Stress Fractures: A Case Report. J Orthop Case Rep. 2025 Dec;15(12):32-35. doi: 10.13107/jocr.2025.v15.i12.6444. PMID: 41509769; PMCID: PMC12778937. 5. Clarke BL, Wynne AG, Wilson DM, Fitzpatrick LA. Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features. Clin Endocrinol (Oxf) 1995;43:479–490. doi: 10.1111/j.1365-2265.1995.tb02621.x. 6. (2004). The Metabolic and Molecular Bases of Inherited Disease (Scriver, C. R., Beaudet, A. L., Sly, W. S., Valle, D., Childs, B., Kinzler, K. W., and Vogelstein, B., eds., 8th ed., McGraw-Hill, New-York, 2001, 7012 p. Biochemistry (Moscow), 67, 611-612. 7. Klootwijk ED, Reichold M, Unwin RJ, Kleta R, Warth R, Bockenhauer D. Renal Fanconi syndrome: taking a proximal look at the nephron. Nephrol Dial Transplant. 2015;30:1456–1460. doi: 10.1093/ndt/gfu377. 8. Richards P, Chamberlain MJ, Wrong OM, 1972 Treatment of osteomalacia of renal tubular acidosis by sodium bicarbonate alone. Lancet 2: 994-997. doi.org/10.1016/S0140-6736(72)92405-1. 9. Pham T, Furno-Steib S, Daumen-Legré V, Acquaviva PC, Lafforgue P. Bilateral symmetric polyarthralgia revealing Fanconi's syndrome. Joint Bone Spine. 2002 Mar;69(2):209-13. doi: 10.1016/s1297-319x(02)00383-4. PMID: 12027314. 10. Tsilchorozidou T, Yovos JG. Hypophosphataemic osteomalacia due to de Toni-Debre-Fanconi syndrome in a 19-year old girl. Hormones (Athens). 2005 Jul-Sep;4(3):171-6. doi: 10.14310/horm.2002.11156. PMID: 16613828.