Clinical Chemistry 46: 1868-1869, 2000;
(Clinical Chemistry. 2000;46:1868-1869.)
© 2000 American Association for Clinical Chemistry, Inc.
Transient Hyperphosphatasemia of Infancy and Childhood: Study of 194 Cases
Darina Behúlová1,a,
Vladimír Bzdúch2,
Darina Hole
ová1,
Alena Vasilenková1 and
Jozef Ponec1
1
Department of Clinical Biochemistry, and,
2
1st Pediatric Clinics, University Children’s Hospital, Limbová 1 , 833 40 Bratislava, Slovakia
a Author for correspondence. Fax 421-7-54-788361.
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To the Editor:
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Transient hyperphosphatasemia of infancy and childhood (TH) is a
temporary and isolated increase of serum alkaline phosphatase (ALP; EC
3.1.3.1) activity occurring without obvious cause during the first
years of life. Despite several reports about this phenomenon, the
origin of TH remains obscure.
Over a period of 8 years (1992–1999), we detected 194 cases of TH in
106 boys and 88 girls. The hyperphosphatasemia was discovered
fortuitously during routine investigations in outpatient and inpatient
departments of a children’s hospital with a capacity of 500 beds. A
wide variety of clinical disorders was associated with this condition
(gastrointestinal diseases, 24%; respiratory infections, 21%;
congenital anomalies and inborn errors of metabolism, 15%; anemia,
10%; malignancies, 7%; neurological disorders, 5%; others, 18%).
We measured total ALP activity using the IFCC-recommended method at
37 °C with Elan (Eppendorf) and Cobas Integra (Roche) analyzers. Our
reference interval for children was 0.85–6.80 µkat/L (51–408 U/L).
Adult reference intervals are 0.54–1.7 µkat/L (32–104 U/L) for
women and 0.76–2.0 µkat/L (45–122 U/L) for men. In each TH case, we
saw the characteristic two-band ALP isoenzyme pattern on Cellogel zonal
electrophoresis as described by Stein et al. (1) and
Behúlová et al. (2).
Although markedly increased ALP activities may occur in TH, frequently
only slightly or moderately increased activities are observed,
depending on the timing of the blood sample in relation to the natural
course of TH. Markedly increased activities, therefore, are not
necessary to reach a diagnosis of TH. The peak ALP activity in our
series was 2- to 20-fold higher than the pediatric upper reference
limit, with the median being a 4-fold increase.
In this series, 49% of cases were detected in the second year of life,
and 96% of affected children were younger than 5 years (Fig. 1
). We speculate that immaturity of the mechanisms responsible
for ALP clearance allows increases of plasma ALP, triggered by an
exogenous insult.
We observed a marked seasonal clustering of cases from September to
November (43%); the lowest incidence was from January to March (13%).
Similar seasonal differences were described previously in a smaller
series (3). In addition, we discovered a simultaneous course
of TH in three sets of twins and two other sibling pairs (neither
parent was affected). "Epidemic" incidence and familial occurrence
strongly support a relationship of TH with viral, protozoal, or other
infections (4)(5). On the other hand, these
findings might suggest a genetic predisposition for a unique response
to any infection.
In our department of clinical biochemistry, ALP isoenzyme
electrophoresis has been used for differential diagnosis of TH and
organic hyperphosphatasemias. Over the last 8 years, ALP isoenzyme
measurements were requested in 562 children under 5 years of age. We
detected TH in 187 patients (33%) and hyperphosphatasemia of
predominantly bone, intestine, or liver origin in 336 (60%), 21 (4%),
and 18 (3%) patients, respectively. To our knowledge, we report the
largest series of TH children that has been identified in one hospital.
We conclude that TH cannot be regarded as a rare or exceptional
syndrome (6) and that it belongs among the diagnostic tasks
in present-day pediatric chemistry.
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References
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Stein P, Rosalki SB, Foo AY, Hjelm M. Transient hyperphosphatasemia of infancy and early childhood: clinical and biochemical features of 21 cases and literature review. Clin Chem 1987;33:313-318.[Abstract/Free Full Text]
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Behúlová D, Bzdúch V, Kasanická A, Tichá L, Kuceková G. Electrophoresis of alkaline phosphatase isoenzymes—the key to rapid diagnosis of transient hyperphosphatasemia [in Slovak]. Cs Pediatr 1993;48:193-195.
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Crofton PM. What is the cause of benign transient hyperphosphatasemia? A study of 35 cases. Clin Chem 1988;34:335-340.[Abstract/Free Full Text]
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Frank U, Kruse K. Evidence for infectious origin of isolated transient hyperphosphatasemia [Letter]. Eur J Pediatr 1985;143:323-324.[ISI][Medline]
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Griffiths J, Vernocchi A, Simoni E. Transient hyperphosphatasemia of infancy and childhood. A study of serum alkaline phosphatase by electrofocusing techniques. Arch Pathol Lab Med 1995;119:784-789.[ISI][Medline]
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Behúlová D, Bzdúch V, Holeová D, Vasilenková A, Mekinová D, Kasanická A. Transient hyperphosphatasemia of infancy and childhood is not a rare condition [Abstract]. Clin Chem Lab Med 1999;37(Suppl):S415.
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