Letter to the Editor
Transient hyperphosphatasemia in a child with nephrolithiasis and severe prematurity
Hiperfosfatasemia transitoria en un niño con nefrolitiasis y antecedentes de prematuridad severa
Stepan Kutileka,b,d,
, Daniela Formanovab, Marian Senkerikb, Jan Langerc, Daniela Markovac, Sylva Skalovad
Autor para correspondencia
kutilek@nemkt.cz
Corresponding author at: Department of Pediatrics, Klatovy Hospital, Plzenska 929, Klatovy, Czech Republic.
Corresponding author at: Department of Pediatrics, Klatovy Hospital, Plzenska 929, Klatovy, Czech Republic.
a Department of Pediatrics, Klatovy Hospital, Klatovy, Czech Republic
b Department of Pediatrics, Pardubice Hospital, Pardubice, Czech Republic
c Department of Pediatrics, University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic
d Department of Pediatrics, University Hospital and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Czech Republic
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"Department of Pediatrics, University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Pediatrics, University Hospital and Faculty of Medicine in Hradec Kralove, Charles University in Prague, Czech Republic" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author at</span>: Department of Pediatrics, Klatovy Hospital, Plzenska 929, Klatovy, Czech Republic." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hiperfosfatasemia transitoria en un niño con nefrolitiasis y antecedentes de prematuridad severa" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Transient hyperphosphatasemia of infancy and early childhood (THI) is a benign, usually accidentally detected condition characterised by transiently increased activity of serum alkaline phosphatase (S-ALP) in children under five years of age, without any signs of metabolic bone disease or hepatopathy corresponding with the increased S-ALP.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–4</span></a> When detected in a child with either chronic bone, liver or kidney disease, THI might may raise significant concerns.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4–6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 13-months’ old boy with a complicated perinatal history (severe prematurity – 26th week of gestation, birthweight 1085<span class="elsevierStyleHsp" style=""></span>g, respiratory distress syndrome, reanimation, neonatal sepsis, pneumonia, artificial ventilation, necrotising enterocolitis, anaemia, hypophosphataemia and osteopathy of prematurity) and resulting bronchopulmonary dysplasia (with consequent furosemide treatment in the infantile period), was hospitalised because of renal colic manifested by painful crying with gross haematuria. Abdominal ultrasound revealed renal stones in each kidney, diameter 3<span class="elsevierStyleHsp" style=""></span>mm on the left and 6<span class="elsevierStyleHsp" style=""></span>mm on the right, respectively. The serum values of blood urea nitrogen (BUN), creatinine, potassium (S-K), sodium (S-Na), calcium (S-Ca), phosphate (S-P), magnesium (S-Mg), alanin-aminotransferase (S-AST), apartate-aminotransferase (S-ALT), parathyroid hormone (S-PTH) were all within normal reference range, same as the urinary concentrations of Ca, P, Mg and urinary calcium/creatinine ratio (U-Ca/U-cr). However S-ALP was 34<span class="elsevierStyleHsp" style=""></span>μkat/L (normal 2.5–9.5<span class="elsevierStyleHsp" style=""></span>μkat/L). Wrist X-ray was normal without any signs of rickets. As rickets was ruled out, vitamin D levels were not assessed. The only possible relationship between vitamin D and urolithiasis could have been either vitamin D overdosage or hypophosphatemic rickets with hypercalciuria. As S-Ca, S-P and U-Ca/U-cr were all normal and rickets was ruled out, these possibilities were out of question. Hematuria resolved within 3 days. As there were neither laboratory nor clinical signs of liver or bone disease, THI was considered as the most likely diagnosis. Concerning the kidney stones management, conservative approach including periodic ultrasound assessment was decided. The boy was dismissed on day 4 and checked 28 days later. At that time the S-ALP dropped to normal value of 9.2<span class="elsevierStyleHsp" style=""></span>μkat/L. S-Ca, S-P were also normal. Therefore the patient fulfilled the criteria for THI. There were no further increases in S-ALP and the patient, who is currently 18 months old, remains stable and is periodically checked on an out-patient basis.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our patient had a history of prematurity, and according to the hospital records, hypophosphatemia occurred throughout 3rd and 4th month of age, thus indicating history of resolved osteopathy of prematurity.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Osteopenia or osteopathy of prematurity (metabolic bone disease of preterm infants or metabolic bone disease of prematurity) is defined as decreased bone mineral content that occurs mainly as a result of lack of adequate phosphate and calcium intake in extrauterine life. The incidence of metabolic bone disease of prematurity among infants born before 28 weeks of gestational age is as high as 30% and it usually occurs between 6 and 12 weeks of age, however the laboratory signs of impaired mineral metabolism can be detected as early as in the 3rd or 4th week of life. The principal cause of disturbed mineral metabolism and metabolic bone disease of prematurity is phosphate depletion, manifested by hypophosphatemia.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a> The infant tends to retain maximum amount of phosphate, this resulting in hypophosphaturia and high renal tubular phosphate reabsorption. Due to phosphate depletion, the PTH secretion is low. Furthermore, the calcium accretion in the skeleton is also impaired, which might result in hypercalcemia and, in particular, in hypercalciuria with consequent urolithiasis.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Furthermore, treatment with furosemide in the infantile period could have also increased calciuria in our patient. Transient hyperphosphatasemia is a benign condition with good prognosis, that has been so far reported in more than 800 subjects, both sick and healthy children. The basic diagnostic criteria include an age of less than 5 years; variable, unrelated symptoms; no bone or liver disease noted on physical examination or from laboratory investigations; isoenzyme and isoform analysis showing elevations in both bone and liver activity, and a return to normal S-ALP values within four months.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–6,10</span></a> The incidence of THI has been estimated at 2.8%.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> THI is rather a laboratory than clinical finding and can cause some concern in patients with metabolic bone disorders, kidney or liver disease.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–6</span></a> Normal bone turnover was previously observed in children with THI.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3–6</span></a> Our patient with bilateral nephrolithiasis and a history of severe prematurity presented with high S-ALP, initially suggestive of disturbed bone metabolism. However, the normal values of S-Ca, P, Mg, PTH, U-Ca/U-cr and normal wrist X-ray ruled out this possibility and pointed to the diagnosis of THI, which was further confirmed by the normalisation of S-ALP within one month. The present nephrolithiasis was considered as a result of previous hypercalciuria in osteopathy of prematurity, that has already resolved without causal relationship to transiently increased S-ALP.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion, children with THI should be spared from unnecessary frequent diagnostic procedures and therapeutic interventions.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transient benign hyperphophatasemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Gualco" 1 => "S.A. Lava" 2 => "L. Garzoni" 3 => "G.D. Simonetti" 4 => "A. Bettinelli" 5 => "G.P. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 11 | 11 | 22 |
| 2024 Octubre | 65 | 36 | 101 |
| 2024 Septiembre | 89 | 20 | 109 |
| 2024 Agosto | 103 | 89 | 192 |
| 2024 Julio | 69 | 28 | 97 |
| 2024 Junio | 84 | 34 | 118 |
| 2024 Mayo | 119 | 40 | 159 |
| 2024 Abril | 79 | 40 | 119 |
| 2024 Marzo | 75 | 31 | 106 |
| 2024 Febrero | 74 | 40 | 114 |
| 2024 Enero | 55 | 23 | 78 |
| 2023 Diciembre | 70 | 32 | 102 |
| 2023 Noviembre | 73 | 28 | 101 |
| 2023 Octubre | 76 | 39 | 115 |
| 2023 Septiembre | 73 | 25 | 98 |
| 2023 Agosto | 76 | 26 | 102 |
| 2023 Julio | 49 | 21 | 70 |
| 2023 Junio | 56 | 27 | 83 |
| 2023 Mayo | 94 | 33 | 127 |
| 2023 Abril | 75 | 23 | 98 |
| 2023 Marzo | 70 | 31 | 101 |
| 2023 Febrero | 67 | 21 | 88 |
| 2023 Enero | 56 | 28 | 84 |
| 2022 Diciembre | 50 | 47 | 97 |
| 2022 Noviembre | 97 | 51 | 148 |
| 2022 Octubre | 63 | 71 | 134 |
| 2022 Septiembre | 60 | 51 | 111 |
| 2022 Agosto | 56 | 56 | 112 |
| 2022 Julio | 48 | 70 | 118 |
| 2022 Junio | 70 | 37 | 107 |
| 2022 Mayo | 52 | 34 | 86 |
| 2022 Abril | 97 | 91 | 188 |
| 2022 Marzo | 84 | 66 | 150 |
| 2022 Febrero | 58 | 50 | 108 |
| 2022 Enero | 50 | 48 | 98 |
| 2021 Diciembre | 61 | 50 | 111 |
| 2021 Noviembre | 59 | 40 | 99 |
| 2021 Octubre | 71 | 49 | 120 |
| 2021 Septiembre | 35 | 43 | 78 |
| 2021 Agosto | 38 | 53 | 91 |
| 2021 Julio | 35 | 43 | 78 |
| 2021 Junio | 31 | 33 | 64 |
| 2021 Mayo | 38 | 42 | 80 |
| 2021 Abril | 94 | 109 | 203 |
| 2021 Marzo | 44 | 48 | 92 |
| 2021 Febrero | 45 | 46 | 91 |
| 2021 Enero | 36 | 33 | 69 |
| 2020 Diciembre | 35 | 28 | 63 |
| 2020 Noviembre | 32 | 20 | 52 |
| 2020 Octubre | 30 | 33 | 63 |
| 2020 Septiembre | 36 | 24 | 60 |
| 2020 Agosto | 35 | 34 | 69 |
| 2020 Julio | 25 | 29 | 54 |
| 2020 Junio | 40 | 36 | 76 |
| 2020 Mayo | 23 | 34 | 57 |
| 2020 Abril | 30 | 25 | 55 |
| 2020 Marzo | 36 | 18 | 54 |
| 2020 Febrero | 38 | 32 | 70 |
| 2020 Enero | 50 | 24 | 74 |
| 2019 Diciembre | 51 | 29 | 80 |
| 2019 Noviembre | 36 | 31 | 67 |
| 2019 Octubre | 24 | 17 | 41 |
| 2019 Septiembre | 29 | 20 | 49 |
| 2019 Agosto | 24 | 28 | 52 |
| 2019 Julio | 22 | 27 | 49 |
| 2019 Junio | 47 | 27 | 74 |
| 2019 Mayo | 28 | 22 | 50 |
| 2019 Abril | 75 | 35 | 110 |
| 2019 Marzo | 46 | 31 | 77 |
| 2019 Febrero | 42 | 24 | 66 |
| 2019 Enero | 37 | 21 | 58 |
| 2018 Diciembre | 147 | 64 | 211 |
| 2018 Noviembre | 304 | 38 | 342 |
| 2018 Octubre | 209 | 26 | 235 |
| 2018 Septiembre | 124 | 28 | 152 |
| 2018 Agosto | 125 | 40 | 165 |
| 2018 Julio | 81 | 30 | 111 |
| 2018 Junio | 110 | 34 | 144 |
| 2018 Mayo | 104 | 40 | 144 |
| 2018 Abril | 159 | 17 | 176 |
| 2018 Marzo | 134 | 22 | 156 |
| 2018 Febrero | 92 | 19 | 111 |
| 2018 Enero | 75 | 15 | 90 |
| 2017 Diciembre | 111 | 18 | 129 |
| 2017 Noviembre | 68 | 23 | 91 |
| 2017 Octubre | 61 | 20 | 81 |
| 2017 Septiembre | 107 | 25 | 132 |
| 2017 Agosto | 150 | 24 | 174 |
| 2017 Julio | 112 | 21 | 133 |
| 2017 Junio | 94 | 16 | 110 |
| 2017 Mayo | 69 | 11 | 80 |
| 2017 Abril | 64 | 17 | 81 |
| 2017 Marzo | 38 | 4 | 42 |
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