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Indian Pediatr 2016;53:
1013-1014 |
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Distal Renal Tubular
Acidosis Associated with Celiac Disease and Thyroiditis
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Amit Kumar Satapathy, Sapna Mittal and Vandana Jain
From Department of Pediatrics, All India Institute of
Medical Sciences, New Delhi, India.
Correspondence to: Dr Vandana Jain, Additional
Professor, Division of Pediatric Endocrinology, Department of
Pediatrics, AIIMS, New Delhi 110 029, India. [email protected]
Received: December 21, 2015;
Initial review: March 07, 2016;
Accepted: July 13, 2016.
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Background: Association of distal renal
tubular acidosis (RTA) with autoimmune diseases is extremely rare in
children.Case Characteristics: 12-year-old girl with distal RTA.
Despite resolution of acidosis on bicarbonate, she continued to have
poor growth and delayed puberty. Investigations revealed autoimmune
thyroiditis and celiac disease. Outcome: Levothyroxine and
gluten-free diet were initiated. Child gained height and weight and had
onset of puberty after gluten withdrawal. Messages: Distal RTA in
children may rarely be of autoimmune etiology.
Keywords: Autoimmune diseases, Hypothyroidism, Metabolic
acidosis, Refractory rickets
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Distal renal tubular acidosis (RTA) is an
important cause of refractory rickets and failure to thrive in children.
Rarely, distal RTA may be of autoimmune etiology, as suggested by its
association with other autoimmune conditions such as Sjogren syndrome,
systemic lupus erythematosus (SLE) and Hashimoto’s thyroiditis. Herein
we present a girl with distal RTA with celiac disease and thyroiditis.
Case Report
A 12-year-old girl with vitamin-D resistant rickets
was referred to us. Her height and BMI were 121.5 cm and 13.4 kg/m 2
(both below the 3rd centile). The child had been
born to a non-consanguineous couple, with no significant past or family
history. Investigations revealed high serum 25OHD, normal anion gap
metabolic acidosis, hypo-kalemia and alkaline urine (Table I),
suggesting a possibility of renal tubular acidosis. Further tests
revealed bilateral nephrocalcinosis and hypercalcuria. Phos-phaturia and
generalized aminoaciduria were absent. Urinary-Blood CO2
after bicarbonate loading test also favoured the diagnosis of distal
RTA. Child was started on oral bicarbonate at the dose of 2 meq/kg/day
along with potassium supplementation and hydrochlorthiazide.
TABLE I Laboratory Parameters at Initial Presentation and After 24 months
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Initial |
Follow up |
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presentation |
(24 months) |
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Hemoglobin (g/dL) |
8.9 |
10.4 |
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Calcium (mg/dL) |
8.2 |
9.3 |
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Phosphate (mg/dL) |
2.3 |
5.3 |
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SAP (IU/L) |
1489 |
1052 |
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Creatinine (mg/dL) |
0.5 |
0.4 |
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pH |
7.31 |
7.34 |
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HCO3 (mEq/L) |
14.8 |
19.3 |
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K+ (mEq/L) |
3.2 |
3.8 |
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FePO4 (%) |
24 |
18 |
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TMP GFR |
2.6 |
2.6 |
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Ur calcium (mg/kg/d) |
6 |
13 |
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Ur calcium/creatinine ratio |
0.4 |
0.7 |
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Ur pH |
6.3 |
6.9 |
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T4 (ng/ml) |
5.9 |
7.5 |
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TSH (mIU/L) |
7.8 |
0.87 |
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FePO4: Fractional excretion of phosphate; Ur; Urinary; SAP:
Serum alkaline phosphatase. |
On follow-up, rachitic changes resolved and blood gas
and serum potassium normalized, but growth continued to be poor, with
delayed bone age and delayed puberty. Thyroxine supplementation was
initiated in view of persistent mild elevation of TSH, borderline low T4
and positive anti-thyroperoxidase (anti-TPO) antibodies (49.8 IU/mL,
normal <30IU/mL), but no improvement in growth was noted.
Child was also observed to have pallor on subsequent
visits. Peripheral smear showed microcytic hypochromic anemia. Anti-endomysial
antibodies were strongly positive. Duodenal biopsy revealed changes
compatible with Marsh 3 criteria for celiac disease. Child was started
on gluten-free diet at 13.5 years of age, after which she showed
dramatic improvement in height velocity. Presently, at 16 years of age,
child is on gluten-free diet along with soda bicarbonate, potassium and
thyroxine supplements. She has no bony deformities, her height is 150
cm, BMI is 16 kg/m2 and she
has attained menarche.
We considered the possibility that celiac disease
itself may have led to rickets and hypokalemia due to malabsorption.
However, lack of response to injectable vitamin D, persistence of
rickets despite high serum 25OHD levels, and presence of metabolic
acidosis and nephrocalcinosis went against this hypothesis. A trial of
reduction in dose of alkali supplement resulted in reappearance of
metabolic acidosis. Hence, our final diagnosis is distal RTA (of
possible autoimmune etiology), with celiac disease and hypothyroidism
due to Hashimoto’s thyroiditis. Anti-nuclear antibody (ANA) was negative
for the child. Child is under regular follow up and we are vigilant for
the appearance of other associated autoimmune manifestations.
Discussion
Distal RTA is a rare condition and no estimate of its
prevalence in Indian population is available. Inherited form of distal
RTA is most commonly due to autosomal recessive mutations in genes
encoding subunits of the vacuolar H +ATPase,
resulting in impaired transporter function in the renal tubule [2].
Acquired impaired transporter function of the H +
secreting machinery is more common in adults, and
is often associated with autoimmune conditions like Sjögren syndrome
[3]. Other autoimmune diseases such as SLE [4], primary biliary
cirrhosis [5], autoimmune hepatitis [6], thyroiditis and pernicious
anemia [7] are also uncommonly associated with distal RTA. The exact
target of autoimmunity in the pathogenesis of distal RTA is not clear.
In patients with primary Sjögren syndrome, inhibitory autoantibodies
against the enzyme carbonic anhydrase II have been reported [3], and in
patients with distal RTA and pernicious anemia, antibodies against
intercalated cells with possible cross-reactivity against structures
containing the gastric H1/K1-ATPase pump have been reported [7].
Our patient had an association of celiac disease with
autoimmune thyroiditis and distal RTA. Patients with celiac disease
commonly have other autoimmune conditions as well. This is probably
secondary to a generalized abnormal immunological response to
gluten-derived protein, leading to production of several
auto-antibodies. Type 1 diabetes and autoimmune thyroiditis are the most
commonly associated autoimmune conditions with celiac disease. Other
associated conditions include Graves disease, IgA nephropathy,
autoimmune hepatitis, primary sclerosing cholangitis and gluten ataxia
[8]. HLA DQ2 and HLA DQ8 are strongly associated with celiac disease and
screening of HLA subtype can be used to predict the future occurrence of
celiac disease in patients with type 1 diabetes or thyroiditis [8].The
association of celiac disease with Sjogren syndrome and distal RTA in an
adult has been reported previously [9], but the association of celiac
disease with distal RTA without Sjogren syndrome in children has not
been previously reported.
To conclude, we wish to emphasize that distal RTA,
although usually a primary inherited condition in children, can be
secondary to autoimmunity, and be associated with other autoimmune
diseases.
Contributors: VJ, AS: managed the case; AS, SM,
VJ: prepared the manuscript; VJ: critical revisions, and will act as
guarantor.
Funding: None; Competing interest: None
stated.
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