Mom Caught Me in a Baby Pink Diaper

Pediatr Nephrol. Author manuscript; available in PMC 2016 April ane.

Published in concluding edited form equally:

PMCID: PMC4591217

NIHMSID: NIHMS718075

An Unusual Cause of Pink Diaper in An Infant

Rasheda Amin

¹Partition of Pediatric Nephrology, Children's National Health System, Washington, DC

Loai Eid

²Partition of Pediatrics, Latifa Hospital, Dubai, UAE

Vidar O. Edvardsson

³Children'south Medical Heart, Landspitali – The National University Infirmary of Iceland, Reykjavik, Iceland

⁴Kinesthesia of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Republic of iceland

Lynette Fairbanks

^fivePurine Enquiry Laboratory, Viapath, St Thomas' Hospital, London, UK

Asha Moudgil

^aneDivision of Pediatric Nephrology, Children'south National Wellness System, Washington, DC

Case Summary

A 9 month old, Caucasian, male person baby presented for evaluation of intermittent pink diaper staining since the age of 4 months, more than oft observed in the first morning diapers. He was noted to exist straining occasionally while voiding. Additionally, he was not thriving normally (failure to thrive (FTT)) and in the past 5 months his weight had fallen from the 64^thursday to the 8^th percentile and length from the 49^th to the 37^thursday percentile. At that place was no history of fever, chronic diarrhea, urinary tract infections or urinary stone passage. He was the production of a full term gestation and was developmentally normal. He was the first child of non-consanguineous parents and family history was unremarkable. On physical examination, no dysmorphic features were observed and blood force per unit area was normal. The remainder of the physical test was within normal limits.

Initial urinalysis and all laboratory studies including consummate blood count, renal function, liver function, thyroid function, serum magnesium levels, celiac disease console, venous blood gas, parathyroid hormone and 25 OH Vitamin D were within normal reference ranges. Serum uric acid was 0.1mg/dl (reference range 1.4–6.7 mg/dl). Random urine studies revealed normal urine citrate-, oxalate-, and calcium-to-creatinine ratios. Fractional excretion of magnesium and tubular phosphate reabsorption were normal. At that place was no evidence of generalized aminoaciduria. A renal and float ultrasound demonstrated no abnormalities and a radiograph of the wrist was negative for rickets. Urine microscopic examination of get-go forenoon urine revealed numerous crystals (Figure one).

Urine microscopy (40×) showing arrowhead pointing towards a large xanthine crystal with like, smaller crystals in the background.

Questions

1. What are the possible etiologies of crystalluria in an infant?

2. What farther testing can be done in this patient to accomplish a diagnosis?

3. What conditions are associated with hypouricemia?

Answers

1. The possible etiologies of crystalluria in an babe include hypercalciuria, distal RTA (d-RTA), primary hyperoxaluria, cystinuria, hyperuricosuria and rarely an increased excretion of other purine metabolites such as 2,eight-dihydroxyadenine, xanthine and hypoxanthine[1]. Our patient did non have bear witness of metabolic acidosis, hypercalciuria, hypocitraturia, hyperoxaluria or aminoaciduria thereby ruling out crystalluria secondary to disorders causing hypercalciuria, d-RTA, master oxaluria, and cystinuria. We therefore focused further investigation on disorders of purine metabolism. Hyperuricosuria may exist physiologic due to increased excretion of uric acid in neonates. Hyperuricosuria with hyperuricemia may exist associated with hypoxanthine-guanine phosphoribosyl transferase (HPGRT) deficiency and glycogen storage disorders. Adenine phosphoribosyl transferase (APRT) deficiency leads to increased urinary 2,8-dihydroxyadenine excretion wheras mutations in the xanthine dehydrogenase (XDH) gene pb to increased excretion of both xanthine and hypoxanthine.

2. Further testing should include

   • Urinary uric acid-to-creatinine ratio and partial excretion of uric acrid (FeUA) to appraise for hyperuricosuria.

   • APRT enzyme activity in erythrocyte lysates – abolished enzyme activeness confirms APRT deficiency.

   • Urinary xanthine- and hypoxanthine-to-creatinine ratios ߝ increased excretion and low FeUA is suggestive of xanthinuria

   • Urine sulfocysteine level to evaluate for molybdenum cofactor deficiency, which is associated with xanthinuria.

   In our patient, increased urinary excretion of xanthine and hypoxanthine and low FeUA along with severe hypouricemia and normal APRT enzyme activity, were diagnostic of hereditary xanthinuria.

3. Hypouricemia tin exist associated with several conditions which can be further classified based on FeUA [ii]. Depression FeUA is seen in hereditary Xanthinuria and is also associated with the use of allopurinol or rasburicase, and low dietary purine intake. Hypouricemia with normal to high FeUA is seen in hereditary renal hypouricemia, syndrome of inappropriate antidiuretic hormone, Wilson's illness, Fanconi syndrome and Cystinosis.

Commentary

Urinary crystals in this patient did not resemble uric acid or cysteine crystals and in fact, did not resemble any unremarkably establish urinary crystals. Literature review revealed the crystals to closely resemble 2,8-DHA seen in most patients with untreated APRT deficiency. APRT deficiency (OMIM: 614723) is a rare, inherited disorder of purine metabolism that leads to excessive urinary excretion of the highly insoluble two,8-DHA crystals which causes kidney stones, chronic kidney disease and even cease-stage renal disease [iii]. Diagnosis is confirmed by macerated APRT action in red claret cell lysates. Serum uric acrid level is normal [iv]. Although the proband's crystals resembled ii,8-DHA, his APRT enzyme activity in erythrocyte lysate was normal at 36 nmol/h/mgHB (reference range 17–32 nmol/h/mgHB) excluding this diagnosis.

The findings of increased urinary excretion of xanthine and hypoxanthine, at 203 mmol/mol creatinine (Cr) (reference <53mmol/mol Cr) and 414 mmol/mol Cr (reference <49mmol/mol Cr), respectively, extremely depression partial excretion of uric acid at 0.25% (normal seven.28±two.9%) and hypouricemia in our patient were highly suggestive of xanthinuria. Urine sulfocysteine level was normal at 7 micromol/g Cr (reference range <80micromol/g Cr) thus ruling out molybdenum cofactor deficiency as the cause of xanthinuria. Genetic testing of the proband revealed one previously described heterozygous mutation, T910M, in exon 25 of the xanthine dehydrogenase (XDH) gene (c.2729C>T) and a second, previously unidentified, heterozygous variant, R830C, in exon 23 of the XDH cistron (c.2488C>T). [5, 6]. The proband'south asymptomatic female parent was heterozygous for the T910M mutation and his asymptomatic father was heterozygous for the R830C variant.

Further management of our patient involved a low purine nutrition in improver to maintenance of hydration specially in the confront of an acute illness. One and a one-half yr after initial presentation, body weight has increased to the 27^thursday percentile and height to the 61^st percentile. The kid is mostly asymptomatic but is still noted to accept crystals in the get-go morning urine during episodes of acute disease. Microscopic exam of first forenoon urine specimens on multiple occasions has failed to show any crystals during illness costless periods. Nonetheless, urine xanthine- and hypoxanthine-to-creatinine ratios (mmol/mol) remain elevated at 731 and 248, respectively. Repeat renal ultrasound is normal.

Hereditary xanthinuria is an autosomal recessive disorder of purine metabolism almost commonly manifesting with urolithiasis and in rare cases, renal failure due to crystal nephropathy [7]. The disorder is caused by mutations in the XDH factor located on chromosome 2p23 causing deficiency of the XDH enzyme responsible for degradation of hypoxanthine and xanthine to uric acid [eight]. Deficiency of XDH results in markedly diminished production of uric acid and elevated xanthine and hypoxanthine levels in plasma and urine (Figure 2). Loftier renal clearance and farthermost insolubility at any physiological pH can cause xanthine crystal precipitation in the renal tubules leading to crystalluria, hematuria, urorolithiasis, and in astringent cases, renal failure [seven]. Infants tin can additionally present with FTT and urinary tract infection. Renal manifestations tin present at any age, with more than fifty pct occurring in children younger than 10 years. In older patients, accumulation of xanthine in extra-renal tissues may cause duodenal ulcers, myopathy or arthropathy. Near twenty percentage of patients have been reported to be asymptomatic [7]. The incidence appears to exist higher in Mediterranean and Centre Eastern populations [nine, ten].

Cartoon of purine metabolism pathway. Deoxyribonucleic acid: Deoxyribonucleic acid; RNA: Ribonucleic acid; XDH: Xanthine dehydrogenase.

Xanthinuria is classified into 2 types based on the enzyme deficiency. In type I (OMIM 278300), there is an isolated deficiency of XDH whereas in blazon II (OMIM: 603592), there is an additional deficiency of the enzyme aldehyde oxidase (AOX) responsible for metabolism of allopurinol [11]. Diagnosis is made by identification of crystals, high urinary xanthine and hypoxanthine levels, depression serum uric acid levels and low FeUA. Genetic testing is also available. To engagement in that location are seven reported mutations causing xanthinuria blazon 1 in the Human Gene Mutation Database (HGMD®) [12]. Four of these are nonsense or missense mutations, ii are small deletions and i constitutes a small insertion [5, 8, ten, 13–xv].

Xanthinuria can as well be associated with molybdenum cofactor deficiency (OMIM: 252150) where sulfite oxidase (SO) is too inactive in improver to XDH and AOX and is characterized by severe neurologic involvement. Molybdenum cofactor is essential for the part of the SO, XDH and AOX. Diagnosis is fabricated on the basis of hypouricemia, elevated urinary xanthine and South-sulfocysteine levels [xvi].

Hereditary xanthinuria is managed with high fluid intake and a diet low in purines. Urine alkalinization is ineffective every bit xanthine is insoluble at any physiological pH. Response to treatment tin be monitored by urine microscopy looking for crystalluria, and by periodic monitoring of urinary xanthine and hypoxanthine excretion.

Conclusion

This clinical quiz highlights the importance of urine microscopy performed by the clinician for detection of crystalluria. It is important to examine a first morn specimen for the best yield. It is alarming to notation that manual urine microscopy is not routinely performed in many nephrology practices and comes at the cost of losing valuable information gained from this simple process [17]. In addition, this case also underscores the significance of hypouricemia equally an of import laboratory finding that can aid in diagnosis of a kid presenting with urinary crystals.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591217/

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