A rare mutation in hypophosphatasia: a case report of adult form and review of the literature

SUMMARY Hypophosphatasia is a rare inborn error of metabolism characterized by low serum alkaline phosphatase activity due to loss-of-function mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Extracellular accumulation of TNSALP substrates leads to dento-osseous and arthritic complications featuring tooth loss, rickets or osteomalacia, and calcific arthopathies. Mild hypophosphatasia usually has autosomal dominant inheritance, severe cases are either autosomal recessive or due to a dominant negative effect. Clinical manifestations of hypophosphatasia are extremely variable, ranging from life threatening to asymptomatic clinical presentations. The clinical presentation of the adult-onset hypophosphatasia is highly variable. Fractures, joint complications of chondrocalcinosis, calcifying polyarthritis and multiple pains may reveal minor forms of the disease in adults. It is important to recognize the disease to provide the best supportive treatment and to prevent the use of anti-resorption drugs in these patients. Bone-targeted enzyme-replacement therapy (asfotase alfa) was approved in 2015 to treat pediatric-onset hypophosphatasia. We present a case of a 41-year-old male diagnosed with adult form of hypophosphatasia with a rare ALPL mutation that has been previously described only once and review the literature on the adult form of the disease and its genetic mechanism.

PEG-asparaginase induced severe hypertriglyceridemia

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.