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Lesch‐Nyhan syndrome: a novel complex mutation with severe phenotype
Author(s) -
Gucev Z,
Koceva S,
Marinaki A,
Fairbanks L,
Kirovski I,
Tasic V
Publication year - 2010
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2010.01428.x
Subject(s) - medicine , medical genetics , university hospital , pathology , genetics , biology , gene
To the Editor : Lesch-Nyhan disease (LND) is an inborn defect of purine metabolism caused by a deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT). The defect causes overproduction of uric acid. The degree of enzymatic deficiency is variable and causes a spectrum of neurologic, extraneurologic manifestations and a tendency toward self-injury (1, 2). LND is an X-linked recessive disorder, but ∼30% of patients carry de novo mutations (2). Our patient had uneventful antenatal history. Reddish sandy material in the diapers was observed, and at the age of 22 months the child could not seat, stand or walk, he was irritable, with extrapyramidal manifestations, self-injurious behavior, mental and motor retardation. A diagnosis of cerebral palsy was suspected. Renal ultrasound revealed bright, hyperechogenic medullae mimicking bilateral nephrocalcinosis (Fig. 1). His plasma uric acid was elevated at 760 μmol/l (normal range for age 100–260 μmol/l), and he had an elevated uric acid/creatinine ratio of 3.4 (normal for age <1.5) (Table 1). HPRT activity was completely deficient (0, control range 80–130 nmol/mg Hb/h). Adenine phosphoribosyltransferase (APRT) measured as a control enzyme was elevated (53, control range 16–32 nmol/mg Hb/h), as is usually the case in HPRT deficiency. After commencement of allopurinol at 5 mg/ kg/day and alkalinization of urine, the uric acid to creatinine ratio fell to 1.1 (normal for age <1.5), although the ratio of total oxypurines to creatinine remained markedly elevated at 3.2 (Table 1). The plasma uric acid remained elevated. It is important that the allopurinol dose be titrated against xanthine concentration so as to avoid a xanthine nephropathy. This may be at the expense of an increased serum uric acid. Solubility of uric acid in urine is increased by alkalinization and by increasing and maintaining fluid intake. A recent report (3) suggests rasburicase may be helpful in rapidly decreasing plasma uric acid levels during episodes of acute renal failure and may assist in the management of patients with LND. The compliance to the treatment was very poor. The boy developed progressive chronic renal failure with multiple renal stones, severe inanition and died at the age of 10 years.