SUN-726 Adult Hypophosphatasia Presenting with Soft Tissue Heterotopic Calcific Mass Lesions.

Abstract Disclosure: H. Dihowm: None. H. El Amri: None. G.I. Uwaifo: None. Introduction; Hypophosphatasia (HPP) is a rare genetic disorder caused by ALPL gene mutations, resulting in deficient tissue-nonspecific alkaline phosphatase (TNAP) activity. It has highly variable clinical presentations that has no direct correlation with the specific genetic mutations. Persistently low serum alkaline phosphatase (ALP) activity is a hallmark of the condition. While dental loss, rickets, osteomalacia, osteopenia, osteoporosis, calcific arthropathies, myasthenia, myalgia, chronic fatigue and mood disorders are the most prevalent presentations, the range of clinical phenotypes is extensive and difficult to anticipate or predict based on genetic and/or biochemical findings. We present the case of a patient with HPP who presented with the unique phenotype of soft tissue heterotopic calcific mass lesions. Clinical Case; The patient is 58 yr old postmenopausal lady who presented with chronic arthralgias, myalgias, progressive dental loss (complete edentulism by her 40s), and painful masses in the left axilla, left gluteal + posterior upper thigh, which limited her mobility and ambulation. Review of her clinical records showed persistently low ALP levels (24-29 U/L, n; 44-127) that prompted further investigation. This demonstrated persistently low ALP, low bone-specific ALP (3.6 ug/L, n; 7-22.4), and elevated urinary phosphoethanolamine (PEA); 14mmol/mol, n; <4 with normal BUN + creatinine, calcium, phosphate, and PTH levels. Family history showed multiple relatives with CKD, recurrent kidney stones, premature OA and joint replacements, and persistently low ALP levels. The diagnosis of adult autosomal dominant (AD) HPP was confirmed by the above biochemical findings and +ve genetic testing (C.1132G>C heterozygous ALP gene mutation with 2 additional heterozygous gene variant mutations of uncertain significance; VUS). The patient was started on asfotase alfa therapy with significant improvement in nonspecific myalgia, asthenia, fatigue and mobility within the intervening 1.5 months of therapy. Discussion; Our patient’s clinical presentation is of a rare phenotype (soft tissue heterotopic calcification) thus expanding the heterogeneity of the phenotypic spectrum of HPP. As if often the case, clinical suspicion of the correct diagnosis followed recognition of persistently low serum ALP levels in the patient’s retrospective clinical records. In-depth family history inquiry suggests that our patient may be the proband of a sizeable family cohort with HPP. Conclusions; Adult HPP while rare is likely often unrecognized because of its protean often non- specific and heterogenous clinical phenotypic presentation. Attention to the presence of persistently low ALP serum levels is often the first clue to the correct diagnosis. Our patient adds heterotopic soft tissue mass calcifications to the growing profile of possible clinical presentations of adult HPP. Presentation: Sunday, July 13, 2025