First Korean Case of Infantile Hypophosphatasia with Novel Mutation in ALPL and Literature Review.
Hypophosphatasia is a rare hereditary disorder characterized by defective bone and tooth mineralization and deficiency of tissue non-specific alkaline phosphatase activity. The prognosis for the infantile form is poor, with approximately 50% of patients dying within the first year of life from respiratory failure. We describe the clinical and biochemical findings as well as the molecular analysis of a Korean boy with infantile hypophosphatasia and present a literature review. A 1-month-old boy visited the clinic because of poor feeding, frequent vomiting, hypotonia, and failure to thrive from birth. Laboratory tests revealed high total calcium, low phosphorous, low alkaline phosphatase, low parathyroid hormone, and normal 25-hydroxyvitamin D. Intravenous hydration with normal saline was started, and dietary calcium intake was restricted. Skeletal X-rays showed a markedly increased distance of the anterior fontanelle, impaired mineralization, and rachitic changes in the metaphyses. By Sanger sequencing of the ALPL gene, we identified two heterozygous variants, including a missense (c.334G>A; p.Gly112Ser) and a nonsense (c.1039C>T; p.Gln347*) variant. The c.334G>A (p.Gly112Ser) variant had previously been reported in a patient with lethal type hypophosphatasia, while the nonsense c.1039C>T (p.Gln347*) variant was novel. In the current case, the accurate diagnosis and prompt intervention-including dietary calcium intake restriction, tracheostomy to prevent progression to respiratory failure, and fundoplication with gastrostomy to ensure the administration of adequate calories-seemed to play an important role for avoiding preventable morbidity and premature mortality.
Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Eu Gene
EG
Park
Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea nadri1217@naver.com.
Sung Yoon
SY
Cho
Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jeehun
J
Lee
Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jihyun
J
Kim
Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Heeyeon
H
Cho
Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jinsup
J
Kim
Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Rimm
R
Huh
Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chang-Seok
CS
Ki
Department of Radiology, Woorisoa Children's Hospital, Seoul, Republic of Korea.
Ok-Hwa
OH
Kim
Departments of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea jindk@skku.edu.
Dong-Kyu
DK
Jin
D000469:Alkaline Phosphatase / Q000235:genetics*; D001483:Base Sequence; D018488:Bone Demineralization, Pathologic / Q000150:complications; D006801:Humans; D007014:Hypophosphatasia / Q000201:enzymology* / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D056910:Republic of Korea; D012886:Skull / Q000473:pathology
D000469:Alkaline Phosphatase
ALPL; Hypophosphatasia; alkaline phosphatase; hypercalcemia; mineralization