Physical Examination Finding in Hypophosphatemic Rickets
The most likely finding is shortened fourth and fifth metacarpals (Answer C), which is the classic skeletal manifestation of pseudohypoparathyroidism (PHP), a condition that presents with the biochemical profile described in this patient.
Clinical Reasoning
This patient's presentation strongly suggests pseudohypoparathyroidism (PHP), specifically Albright hereditary osteodystrophy, based on the constellation of findings 1:
- Short stature with stocky build
- Muscle weakness and cramps (reflecting end-organ resistance to PTH)
- Hypophosphatemia (PO4 1.8 mg/dL, below normal range)
- Slightly elevated PTH (22.1 pmol/L, upper limit of normal or mildly elevated)
- Low-normal calcium (2.05 mmol/L)
The biochemical pattern reveals PTH resistance rather than PTH deficiency—the elevated PTH fails to maintain normal phosphate levels, indicating end-organ unresponsiveness 1.
Distinguishing Skeletal Features
Brachydactyly pattern in PHP specifically affects the fourth and fifth metacarpals, creating the pathognomonic "knuckle-knuckle-dimple-dimple" sign when the patient makes a fist 1. This is a major diagnostic criterion for PHP and distinguishes it from other causes of hypophosphatemia.
Why Not Other Options:
- Shortened first metacarpal (A): Not characteristic of PHP; more associated with other skeletal dysplasias
- Shortened second and third metacarpals (B): Atypical pattern for PHP
- Shortened first phalanx (D): Less specific than metacarpal involvement
- Shortened radius (E): Not a typical feature of PHP
Differential Considerations
While X-linked hypophosphatemia (XLH) also presents with hypophosphatemia, muscle weakness, and short stature 2, several features argue against it:
- XLH typically shows inappropriately normal or elevated FGF23 levels (not measured here) 2
- XLH patients have lower limb deformities (bowing) rather than brachydactyly 2
- The slightly elevated PTH is more consistent with PHP's resistance pattern than XLH's compensatory response 1
Clinical Pitfalls
Common diagnostic errors include:
- Mistaking PHP for simple vitamin D deficiency—however, PHP patients have normal or elevated PTH with end-organ resistance, not deficiency 1
- Overlooking the skeletal examination—brachydactyly may be subtle in early cases and requires careful palpation of all metacarpals 1
- Failing to recognize that PHP can present with normocalcemia in some cases, as PTH resistance affects phosphate handling more prominently than calcium 3
Confirmatory Testing
The diagnosis should be confirmed by:
- Genetic testing for GNAS mutations (most common in PHP type 1A) 1
- PTH infusion test showing blunted urinary cAMP and phosphate response 1, 3
- Radiographic evaluation of hands demonstrating shortened fourth and fifth metacarpals 1
The patient requires multidisciplinary evaluation including screening for TSH resistance, growth hormone deficiency, hypogonadism, early-onset obesity, and neurocognitive impairment, all of which are associated features of PHP 1.