Hypophosphatasia Presenting As Pseudogout in a Young Woman
Presentation Number: SUN 300
Date of Presentation: April 2nd, 2017
Se Young Suh* and Michael Grimes
Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA
Hypophosphatasia (HPP) is a rare inborn-error-of-metabolism characterized biochemically by low serum alkaline phosphatase (ALP) activity. It is caused by a loss-of-function mutation within the gene that encodes the tissue-nonspecific isoenzyme of ALP (TNSALP). Deficiency of TNSALP leads to extracellular accumulation of TNSALP phosphorylated substrates, including inorganic pyrophosphate (PPi), which is an inhibitor of mineralization, and pyridoxal 5’-phosphate, an intracellular bioactive form of vitamin B6. The range of expressivity of HPP ranges from stillbirth, rickets/osteomalacia, tooth loss, to adult onset calcific arthropathies, largely determined by the autosomal dominant or recessive inheritance of several hundred known TNSALP missense mutations.
A 29 year old Caucasian female presented with chronic joint pain in her hands, feet, hips, back, and shoulders. She started to experience joint pain at age eight, and it progressively worsened over the years. The most affected areas were her hands and feet, which limited her activities of daily living, especially walking. For pain control, she takes ibuprofen 400 mg twice daily, but sometimes takes up to 2000 mg per day when she has an acute exacerbation of joint pain. She was previously diagnosed with fibromyalgia. She was evaluated by a rhematologist and lab testing revealed an elevated ANA titer (1:160), but negative anti-dsDNA antibody, anti-CCP antibody, SS-A and SS-B antibody, Scl-70 antibody, SM/RNP antibody, B2 glycoprotein antibody, and cardiolipin antibody. X-rays of her hands and feet showed erosive arthropathy with calcium pyrophosphate deposition (CPPD) disease and soft tissue calcification.
She had a low ALP level (22 U/L, reference range : 45 -117 U/L) with an elevated vitamin B6 (130.9 ng/mL, reference range: 2.1 to 21.7 ng/mL), which were consistent with laboratory findings of HPP. The patient was heterozygous in the ALPL gene for a variant designated to c.1034C>T, which is predicted to result in the amino acid substitution (p.Ala345Val), which confirmed the diagnosis. To our knowledge this particular variant has not been previously reported in the literature or public database. The patient has a 6 year old daughter who experiences joint pain who also tested positive for an ALPL gene mutation. Notably during her pregnancies, she reported mild improvement of her joint pain.
Young adult patients presenting with chronic polyarthralgias and negative rheumatologic serologies are often diagnosed with fibromyalgia. Although HPP is a rare disorder, physicians should consider this in the differential diagnosis of juvenile onset joint pain with evidence of CPPD. A low ALP level and high serum vitamin B6 level support the diagnosis of HPP. Genetic testing for ALPL gene mutations confirms the diagnosis and may help early diagnosis in other family members.
Nothing to Disclose: SYS, MG