Information for consultants and general practitioners

This information, compiled with the help of St Thomas’ Hospital Purine Research Unit, aims to assist medical professionals by pinpointing significant symptoms.

Purine metabolic disorders are often devastating for the patients involved and their families. Of the twenty-eight known purine metabolic disorders, most have been identified only in the last twenty years and their novelty makes it difficult for clinicians to keep pace. Many existing cases were originally misdiagnosed, or not diagnosed at all until late in life. It is reckoned up to 100 might be born annually in a population of 50 million, on which basis many cases go unrecognised in the UK every year.

Apart from the pain to patients and relatives, the medical cost of misdiagnosis can be immense. Children can be subjected to years of tests and some have progressed to dialysis and transplant.

Symptoms

  • Gout in a young man or woman. Gout in people under thirty is always unusual and should be investigated, not just treated with Allopurinol. Too much Allopurinol can cause kidney damage in young patients with genetic gout.
  • A history of:
    • infections which do not respond to treatment,
    • ‘gravel’ on a child’s nappy, passage of small stones/loin pain.

If you have patients with these symptoms, please consider referring them to a local specialist.

Table of abbreviations

ARF acute renal failure
ADA adenosine deaminase
APRT adenine phosphoribosyltransferase
ASA adenylosuccinase
CDPPT CDP-choline phosphotransferase
DHPA dihydropyrimidinase
DHPD dihydropyrimidine dehydrogenase
FJHN familial juvenile hyperuricaemic nephropathy
HPRT hypoxanthine phosphoribosyltransferase
LNS Lesch Nyhan Disease
MDA myoadenylate deaminase (muscle)
ODC orotidine-5'-decarboxylase
OPRT orotate phosphoribosyltransferase
PNP purine nucleoside phosphorylase
PRPS phosphoribosylpyrophosphatesynthetase superactivity
TPMT thiopurine methyltransferase
UMPH1 uridine monophosphate hydrolase (also known as pyrimidine-5'-nucleotidase)
UMPS uridine monophosphate synthase (OPRT/ODC)
XDH xanthine dehydrogenase
XO xanthine oxidase
XO/SO combined XO/sulphite oxidase

Abnormalities associated with purine and pyrimidine defects

none – 2; cancers – 2; anaemia – 3; immune – 3; drug metabolism – 5; stones – 5; renal – 7; neuralogical – 9

Clinical presentation

disorder associated symptoms diagnostic marker can early diagnosis improve prognosis?
gout and/or renal failure
unknown primary gout in middle-aged male high urate  
LNS partial HPRT deficiency; adolescent gout, ARF, uric acid lithiasis high urate yes (x-linked)
PRPS superactivity gout, uric acid lithiasis, neurological deficits high urate yes (x-linked, females also)
FJHN adolescent gout/progressive renal disease raised urate yes
kidney stones and/or renal failure
XDH deficiency xanthine lithiasis, ARF, arthralgia, myopathy low/absent urate yes
APRT deficiency 2,8-dihydroxyadenine lithiasis   yes
ARF (chemically identical with uric acid stones)    
neurological deficits
ASA deficiency psychomotor retardation with epilepsy    
DHPA deficiency seizures, developmental retardation, spasticity, microcephaly   yes
DHPD deficiency microcephaly, retardation, epilepsy   yes
HPRT deficiency complete HPRT deficiency: LNS, cerebral palsy, self-mutilation, retardation, choreoathetposis, renal complications high urate yes
MDA deficiency muscle cramps, exercise intolerance    
PNP deficiency developmental delay, spasticity, hypertonia, immunodeficiency low urate yes
PRPS superactivity retarded development, ataxia, inherited deafness, dysmorphic features, renal problems high urate yes
XO/SO deficiency (combined deficiency) neonatal fitting, retardation, ocular lens dislocation    
immunodeficiency
ADA deficiency repeated infections, candidiasis, vomiting severe lymphopenia (no T or B cells)  
PNP deficiency life-threatening chicken pox, neurological deficits T cell immunodeficiency, low urate yes
UMPS deficiency cell immunodeficiency, anaemia    
anaemia
UMPS deficiency megalobastic anaemia not responsive to treatment, oroticaciduria, neurological deficits megalobastic anaemia yes (oroticaciduria)
UMPH1 deficiency pyrimidine 5'-nucleotidase haemolytic anaemia T cell immunodeficiency, low urate  
CDPPT haemolytic anaemia    
other
ADA deficiency in pleural/ascites fluid: tuberculosis marker    
TMPT deficiency sufficiency/superactivity: intolerance or non-responsiveness to azathioprine therapy    

Incidence of disorders diagnosed

disorderpercentage of total disorders diagnosed
ADA deficiency 20%
LNS 15.65%
XO deficiency 13.04%
HPRT deficiency 13.04%
APRT 8.7%
pyrimidine defects (CDPPT, UMPH, DHPA, DHPD, UMPS) 6.02%
XO/SO deficiency 5.22%
PNP 3.48%
PRPS 3.48%
TPMT 2.61%

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