Mitsuharu Fukazawa1, Junichiro Tezuka2, Momoko Sasazuki3, Natsuko Masumoto4, Haruhisa Baba4, Takehiko Doi5, Yasushi Tsutsumi4, Yuji Mizuno4, Futoshi Mihara6, Hideki Nakayama7. 1. Department of Pediatrics, National Hospital Organization, Fukuoka Higashi Medical Center, Koga-city, Fukuoka, Japan; Department of Pediatrics, National Hospital Organization, Beppu Medical Center, Beppu-city, Oita, Japan. Electronic address: mitsuharu0720@yahoo.co.jp. 2. Department of Pediatrics, National Hospital Organization, Fukuoka Higashi Medical Center, Koga-city, Fukuoka, Japan; Department of Allergy and Pulmonology, Fukuoka Children's Hospital, Fukuoka, Japan. 3. Department of Pediatrics, National Hospital Organization, Fukuoka Higashi Medical Center, Koga-city, Fukuoka, Japan; Faculty of Health and Welfare, Seinan Jo Gakuin University, Kitakyushu, Fukuoka, Japan. 4. Department of Pediatrics, National Hospital Organization, Fukuoka Higashi Medical Center, Koga-city, Fukuoka, Japan. 5. Department of Pediatrics, National Hospital Organization, Fukuoka Higashi Medical Center, Koga-city, Fukuoka, Japan; Department of Pediatrics, Hiroshima University Institute of Biomedical & Health Sciences, Hiroshima, Japan. 6. Department of Radiology, National Hospital Organization, Fukuoka Higashi Medical Center, Fukuoka, Japan; Department of Radiology, National Hospital Organization Miyazaki Hospital, Koyu District, Miyazaki, Japan. 7. Department of Pediatrics, National Hospital Organization, Fukuoka Higashi Medical Center, Koga-city, Fukuoka, Japan; Department of Pediatrics, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan.
Abstract
BACKGROUND: Hypophosphatasia (HPP) is a rare genetic disorder characterized by rachitic bone manifestations and a low serum alkaline phosphatase (ALP) level. It is caused by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, which encodes the tissue non-specific isozyme of ALP. HPP patients exhibit various presentations depending on their age at onset, such as infantile HPP combined with vitamin B6-responsive seizures. CASE PRESENTATION: A newborn with infantile HPP presented with tonic convulsions from day 5 after birth and received intravenous vitamin B6 (10mg/kg/day pyridoxal phosphate). Eleven days later, frequent apneic episodes occurred, and head magnetic resonance imaging (MRI) showed bilateral reticular formation lesions in the brain stem, including the medulla oblongata. After the pyridoxal phosphate dose was increased (to 40mg/kg/day), the patient's seizures and apnea resolved, and her MRI findings also improved. Genetic testing revealed that she was homozygous for the 1559delT mutation of TNSALP. CONCLUSIONS: High-dose pyridoxal phosphate is a useful treatment for HPP-induced seizures and might improve reticular formation lesions.
BACKGROUND:Hypophosphatasia (HPP) is a rare genetic disorder characterized by rachitic bone manifestations and a low serum alkaline phosphatase (ALP) level. It is caused by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, which encodes the tissue non-specific isozyme of ALP. HPP patients exhibit various presentations depending on their age at onset, such as infantile HPP combined with vitamin B6-responsive seizures. CASE PRESENTATION: A newborn with infantile HPP presented with tonic convulsions from day 5 after birth and received intravenous vitamin B6 (10mg/kg/day pyridoxal phosphate). Eleven days later, frequent apneic episodes occurred, and head magnetic resonance imaging (MRI) showed bilateral reticular formation lesions in the brain stem, including the medulla oblongata. After the pyridoxal phosphate dose was increased (to 40mg/kg/day), the patient's seizures and apnea resolved, and her MRI findings also improved. Genetic testing revealed that she was homozygous for the 1559delT mutation of TNSALP. CONCLUSIONS: High-dose pyridoxal phosphate is a useful treatment for HPP-induced seizures and might improve reticular formation lesions.
Authors: Raffaele Falsaperla; Laura Sciuto; Luisa La Spina; Sarah Sciuto; Andrea D Praticò; Martino Ruggieri Journal: Metab Brain Dis Date: 2021-08-17 Impact factor: 3.584
Authors: Allison L Brichacek; Stanley A Benkovic; Sreeparna Chakraborty; Divine C Nwafor; Wei Wang; Sujung Jun; Duaa Dakhlallah; Werner J Geldenhuys; Anthony B Pinkerton; José Luis Millán; Candice M Brown Journal: Sci Rep Date: 2019-12-11 Impact factor: 4.379