Long-Term Outcome of Paediatric Patients with Hereditary Tubular Disorders

Abstract

Background: An increasing number of children with hereditary tubular disorders (HTD) reach adult life due to diagnostic and therapeutic advances which results in growing need to manage these patients by adult centres. Data on the prevalence and the late clinical problems of these patients are limited. Methods: We observed 177 paediatric patients with isolated or complex HTD between 1969 and 1994. The median age at the time of diagnosis was 3 (range 0–18) years and the median observation period 10 (range 1–43) years. The long-term outcomes with respect to renal function, bone disease, and body growth were analyzed. Results: The prevalence of HTD was 3.2% of all patients observed in our renal unit and 14% of those patients with chronic renal failure and/ or end-stage renal disease. The three most frequent disorders observed were nephropathic cystinosis (n = 34), X-linked hypophosphataemic rickets (n = 26), and idiopathic hypercalciuria (n = 17). At the last observation, 12% of the patients with isolated HTD and 30% of those with complex HTD had developed preterminal chronic renal failure; end-stage renal disease was observed in 5 and 25%, respectively (p < 0.001). Progressive disease occurred mainly in patients having cystinosis, primary hyperoxaluria, the syndrome of hypomagnesaemia/hypercalciuria, primary Fanconi syndrome, Fanconi-Bickel syndrome, and methylmalonic aciduria. Nephrocalcinosis was found in 42%, urolithiasis in 14%, bone deformities and/or fractures in 28%, and other extrarenal alterations in 29% of all patients. The median body height at last observation was 2.0 SD below the normal mean (range from –10.4 to +2.6), and the adult height was subnormal in 48% of 67 grown-up patients. Growth retardation was more severe in complex than in isolated HTD. The mortality decreased from 17% in 1969–1981 to 12% in 1982–1994. Conclusion: Although HTD are rare nephropathies, their frequently progressive course associated with extrarenal complications requires the attention of nephrologists beyond the paediatric age.

Effects of Growth Hormone Treatment on Body Proportions and Final Height Among Small Children With X-Linked Hypophosphatemic Rickets

“…In accordance with this hypothesis, Baroncelli et al 15 reported a sustained increase in the renal phosphate threshold concentration during rhGH treatment. However, we and others 7,12 did not observe consistent effects of rhGH treatment on renal phosphate reabsorption. In addition, the finding of Roy et al 26 that rhGH treatment failed to stimulate renal phosphate reabsorption in Hyp mice argues against a major effect of rhGH treatment on the phosphorous threshold in XLH.…”

“…3 Despite adequate phosphate and calcitriol treatment, most previous studies reported reduced adult height among children with XLH. [4][5][6][7] In addition, children with XLH present with disproportionate growth, ie, relatively preserved trunk growth but severely diminished leg growth. 8 Previous studies demonstrated that treatment with recombinant human growth hormone (rhGH) was able to improve short-and long-term longitudinal growth among small children with XLH.…”

Urinary proteome pattern in children with renal Fanconi syndrome

“…We were unable to correlate the excretion of collagen alpha-1 fragments with the grade of CKD. There is strong evidence in the literature that fibrosis is also the common pathway of renal insufficiency in FS irrespective of the underlying causes [37]. Interestingly, the deregulation of collagen alpha-1 fragments was not only observed in cystinotic patients and CKD grades 3 and 4 but also in those children having CKD grades 2 and 1, indicating that tubular fibrosis starts early in FS and may be the reason for progressive renal failure.…”

Mutation in the Tight-Junction Gene Claudin 19 <i>(CLDN19)</i> and Familial Hypomagnesemia, Hypercalciuria, Nephrocalcinosis (FHHNC) and Severe Ocular Disease

“…Growth failure is a well-documented clinical manifestation in hereditary tubular disorders. However, the median body height in previously reported FHHNC patients varied from –0.9 to –1.7 SDS, while only 1 patient had SDS below –3.0 [5,28] and all patients benefited from the substitution of calcium, calcitriol and hydrochlorothiazide [5]. Sanjad et al [29] recently described extreme short stature (median body height –6.9 SDS) in an FHHNC family with the CLDN16 gene mutation.…”