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
Corresponding author
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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"443" "paginaFinal" => "444" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Stepan Kutilek, Daniela Formanova, Marian Senkerik, Jan Langer, Daniela Markova, Sylva Skalova" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Stepan" "apellidos" => "Kutilek" "email" => array:1 [ 0 => "kutilek@nemkt.cz" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Daniela" "apellidos" => "Formanova" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Marian" "apellidos" => "Senkerik" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Jan" "apellidos" => "Langer" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Daniela" "apellidos" => "Markova" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Sylva" "apellidos" => "Skalova" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Pediatrics, Klatovy Hospital, Klatovy, Czech Republic" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pediatrics, Pardubice Hospital, Pardubice, Czech Republic" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "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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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 9 | 17 |
| 2024 October | 51 | 39 | 90 |
| 2024 September | 48 | 28 | 76 |
| 2024 August | 61 | 62 | 123 |
| 2024 July | 45 | 45 | 90 |
| 2024 June | 41 | 36 | 77 |
| 2024 May | 46 | 26 | 72 |
| 2024 April | 44 | 38 | 82 |
| 2024 March | 37 | 24 | 61 |
| 2024 February | 28 | 29 | 57 |
| 2024 January | 34 | 27 | 61 |
| 2023 December | 25 | 24 | 49 |
| 2023 November | 39 | 26 | 65 |
| 2023 October | 60 | 41 | 101 |
| 2023 September | 50 | 30 | 80 |
| 2023 August | 37 | 24 | 61 |
| 2023 July | 26 | 23 | 49 |
| 2023 June | 33 | 18 | 51 |
| 2023 May | 39 | 25 | 64 |
| 2023 April | 19 | 14 | 33 |
| 2023 March | 36 | 19 | 55 |
| 2023 February | 26 | 25 | 51 |
| 2023 January | 24 | 20 | 44 |
| 2022 December | 44 | 26 | 70 |
| 2022 November | 37 | 35 | 72 |
| 2022 October | 34 | 45 | 79 |
| 2022 September | 33 | 30 | 63 |
| 2022 August | 30 | 37 | 67 |
| 2022 July | 18 | 37 | 55 |
| 2022 June | 29 | 30 | 59 |
| 2022 May | 22 | 36 | 58 |
| 2022 April | 36 | 49 | 85 |
| 2022 March | 22 | 39 | 61 |
| 2022 February | 26 | 36 | 62 |
| 2022 January | 24 | 27 | 51 |
| 2021 December | 27 | 48 | 75 |
| 2021 November | 30 | 35 | 65 |
| 2021 October | 41 | 36 | 77 |
| 2021 September | 15 | 43 | 58 |
| 2021 August | 23 | 42 | 65 |
| 2021 July | 16 | 25 | 41 |
| 2021 June | 20 | 22 | 42 |
| 2021 May | 28 | 34 | 62 |
| 2021 April | 72 | 72 | 144 |
| 2021 March | 33 | 23 | 56 |
| 2021 February | 19 | 37 | 56 |
| 2021 January | 11 | 19 | 30 |
| 2020 December | 13 | 19 | 32 |
| 2020 November | 17 | 14 | 31 |
| 2020 October | 19 | 27 | 46 |
| 2020 September | 17 | 16 | 33 |
| 2020 August | 16 | 14 | 30 |
| 2020 July | 10 | 10 | 20 |
| 2020 June | 26 | 15 | 41 |
| 2020 May | 16 | 11 | 27 |
| 2020 April | 19 | 20 | 39 |
| 2020 March | 15 | 12 | 27 |
| 2020 February | 30 | 20 | 50 |
| 2020 January | 31 | 15 | 46 |
| 2019 December | 19 | 20 | 39 |
| 2019 November | 15 | 16 | 31 |
| 2019 October | 15 | 9 | 24 |
| 2019 September | 16 | 14 | 30 |
| 2019 August | 16 | 9 | 25 |
| 2019 July | 14 | 17 | 31 |
| 2019 June | 24 | 17 | 41 |
| 2019 May | 23 | 11 | 34 |
| 2019 April | 45 | 30 | 75 |
| 2019 March | 29 | 27 | 56 |
| 2019 February | 22 | 17 | 39 |
| 2019 January | 23 | 19 | 42 |
| 2018 December | 90 | 39 | 129 |
| 2018 November | 146 | 20 | 166 |
| 2018 October | 136 | 14 | 150 |
| 2018 September | 100 | 23 | 123 |
| 2018 August | 81 | 12 | 93 |
| 2018 July | 54 | 11 | 65 |
| 2018 June | 51 | 13 | 64 |
| 2018 May | 67 | 13 | 80 |
| 2018 April | 113 | 13 | 126 |
| 2018 March | 79 | 12 | 91 |
| 2018 February | 120 | 9 | 129 |
| 2018 January | 66 | 10 | 76 |
| 2017 December | 116 | 4 | 120 |
| 2017 November | 49 | 11 | 60 |
| 2017 October | 30 | 4 | 34 |
| 2017 September | 56 | 16 | 72 |
| 2017 August | 2 | 1 | 3 |
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