The Case ∣ A child with metabolic acidosis and growth retardation

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The Case ∣ A child with metabolic acidosis and growth retardation
make your diagnosis
http://www.kidney-international.org
& 2009 International Society of Nephrology
Kidney International (2009) 75, 1121–1122; doi:10.1038/ki.2009.25
The Case | A child with metabolic acidosis and growth
retardation
Manisha Sahay1, Sharmas P. Vali1 and Vani D. Ramesh1
1
Department of Nephrology, Osmania Medical College and Hospital, Hyderabad, Andhra Pradesh, India
Correspondence: Manisha Sahay, Department of Nephrology, Osmania Medical College and Hospital, 6-3-852/A, Ameerpet, Hyderabad,
Andhra Pradesh 500016, India. E-mail: [email protected]
Figure 1 | Bony deformities: genu valgum.
Figure 2 | Cornea in slit-lamp picture.
A 6-year-old female child was referred with deformities of
lower and upper limbs (knock knees) since 2 years of age
(Figure 1). A wrist X-ray showed cupping and fraying of
metaphyses. The laboratory evaluation showed serum calcium
8.8 mg/100 ml, phosphorus 3.2 mg/100 ml, alkaline phosphate
1120 (150–600) IU/100 ml, serum creatinine 0.7 mg/100 ml,
blood urea 18 mg/100 ml, serum sodium 140 mequiv./l,
potassium 3.6 mequiv./l, and chloride 118 mequiv./l. Arterial
blood gas analysis showed a pH of 7.3, paCO2 36 mm Hg, paO2
96 mm Hg, and bicarbonate of 19 mequiv./l. Early morning
urine pH was 6.0, and generalized aminoaciduria and
glycosuria were present. Twenty-four-hour urine phosphorus
was 400 (150–375) mg/100 ml. An acid load test was performed
with 1.5 g of oral ammonium chloride administered: the urine
pH after 2 h was 5.1. Slit-lamp examination of the eye is shown
in Figure 2.
What is the acid–base abnormality in this child?
What is the clinical diagnosis?
SEE NEXT PAGE FOR ANSWERS
Kidney International (2009) 75, 1121–1122
1121
make your diagnosis
M Sahay et al.: A child with metabolic acidosis and growth retardation
The Diagnosis | Proximal renal tubular acidosis:
Fanconi syndrome from cystinosis
Slit-lamp examination shows refractile intracellular crystals,
which are pathognomonic for cystinosis in the setting of
Fanconi syndrome.
Cystinosis is a rare genetic disorder affecting 1 in 100, 000
live births. It is caused by the intracellular accumulation of
cysteine due to deficiency of cystinosin, which is required for
the transport of cysteine out of the cells. Cysteine cannot leave
the lysosomes and accumulates as birefringent, hexagonal, or
rectangular crystals within cells of various organ systems. It is
inherited in an autosomal-recessive manner. The gene defect
has been localized to chromosome 17. There are three forms of
cystinosis. Infantile form is the most severe and is characterized
by renal tubular defect—Fanconi syndrome (proximal renal
tubular acidosis, phosphaturia, aminoaciduria, and glycosuria).
Renal failure occurs by adolescence. Other features include
hypothyroidism, delayed puberty, pancreatic disease (exocrine
insufficiency, insulin-dependent diabetes mellitus), liver disease
(hepatosplenomegaly, nodular degenerative hyperplasia), distal
vacuolar myopathy, swallowing difficulties, central nervous
system involvement (calcifications, atrophy, pseudotumor
cerebri), and intracorneal cysteine deposition with resultant
photophobia. Cysteine crystals are present in the cornea and
conjunctiva of the eye and in the bone marrow. Intermediate,
juvenile, or adolescent nephropathic cystinosis is the same as
infantile cystinosis, but occurs at a later age (around the age of
11–15 years). Renal failure occurs in the late teens. Adult
(benign or non-nephropathic) cystinosis does not result in
kidney impairment. Only ocular manifestations are seen.
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Pathognomonic needle-shaped refractile bodies in the
cornea on slit-lamp examination are always found in children
older than 2 years.1 Measurement of the cysteine content of
purified preparations of leukocytes confirms the diagnosis.2
Glomeruli show giant cell transformation of the epithelium,
hyperplasia, and hypertrophy of juxtaglomerular apparatus,
‘dark cells,’ and cytoplasmic inclusions in proximal tubular
cells. Late stages show chronic interstitial nephritis with ‘swan
neck lesions’ due to the degeneration of proximal tubular
cells. Prenatal diagnosis is possible by measuring 35S-labeled
cysteine incorporation into fibroblasts cultured from amniotic fluid or chorionic villi.
Supportive therapy includes correction of metabolic
acidosis, oral phosphorus supplements, carnitine, growth
hormone therapy, and thyroxin. Specific treatment consists of
cysteamine tablets and eye drops. Indomethacin limits
electrolyte and water losses in patients with nephropathic
cystinosis. Kidney transplantation corrects kidney failure but
does not prevent progression of the disease in other nonrenal
organs, and continued therapy with cysteamine is indicated
in patients after kidney transplantation.
REFERENCES
1.
2.
Gahl WA, Kuehl EM, Iwata F et al. Corneal crystals in nephropathic
cystinosis: natural history and treatment with cysteamine eye drops. Mol
Genet Metab 2000; 71: 100–120.
Schneider JA, Bradley K, Seegmiller JE. Increased cystine in leukocytes
from individuals homozygous and heterozygous for cystinosis. Science
1967; 157: 1321–1322.
Kidney International (2009) 75, 1121–1122

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