African Journal of Laboratory Medicine · 3 authors, 2 centres
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This review argues that inborn errors of metabolism (IEMs) can be diagnosed in developing countries using basic, affordable laboratory tests rather than requiring advanced equipment. It provides specific examples of simple diagnostic methods for conditions like phenylketonuria, maple syrup urine disease, and Wilson's disease. The clinical significance is that early detection using these methods can prevent severe morbidity and mortality in resource-limited settings.
**Background:** Inborn errors of metabolism (IEMs) are genetic disorders that impair protein function, often enzymatic, and are collectively common but individually rare. In developing countries, malnutrition, poverty, and limited healthcare access increase the risk of IEMs, yet many clinicians assume diagnosis requires sophisticated laboratory facilities unavailable in these settings. This article aims to demonstrate that basic, affordable tests can detect many IEMs early, enabling timely intervention and preventing irreversible complications.
**Methods:** The authors conducted a quasi-systematic review of the Science Citation Index and PubMed databases, independent of publication date, prioritizing articles from developing countries and by leading authorities. They also included early lectures by Archibald Garrod. A limited synthesis of retrieved articles was performed, acknowledging the cursory nature of the overview.
**Key Results:** The paper details simple diagnostic methods for multiple IEMs: - **Alkaptonuria:** Detected by darkening of standing urine and a positive Benedict's test using copper sulfate in alkaline medium. - **Phenylketonuria:** Diagnosed with the FeCl3 test (10% solution) or Guthrie test, a microbiological assay using Bacillus subtilis and β-2-thienylalanine. Blood phenylalanine levels >2 mg/dL produce bacterial growth. False positives can occur; confirmation by chemical methods or chromatography is recommended. - **Maple syrup urine disease:** Identified by Rothera's test using sodium nitroprusside and ammonium hydroxide, plus the characteristic offensive urine odor (isovaleric aciduria). - **Alpha-1-antitrypsin deficiency:** Suggested by reduced or absent α-band on serum protein electrophoresis combined with abnormal liver function tests. - **Wilson's disease:** Diagnosed by Kayser-Fleischer rings on slit-lamp exam, low serum ceruloplasmin and copper, and elevated urinary copper excretion. - **Cystic fibrosis:** Screened by immunoreactive trypsin in blood; confirmed by sweat chloride ≥60 mmol/L (diagnostic) or <30 mmol/L (unlikely). Pilocarpine iontophoresis is standard. - **Galactosaemia:** Detected by Benedict's test for reducing substances, thin-layer chromatography for urinary galactose, and galactose-1-phosphate uridyltransferase enzyme assay. - **Von Gierke's disease:** Suspected with fasting hypoglycemia and hepatomegaly. - **Urea cycle disorders (e.g., type 1 hyperammonaemia):** Indicated by reduced blood urea, elevated ammonia, elevated transaminases, and coagulopathy. Hyperammonaemia type II shows orotic aciduria. - **Lesch-Nyhan syndrome:** Characterized by elevated uric acid, self-mutilation, and mental retardation. - **Tangier's disease:** Marked by low HDL, absent α-band on electrophoresis, orange-yellow tonsils, and neuropathy. - **Porphyrias:** Diagnosed by elevated porphobilinogen using Ehrlich's reaction (p-dimethylaminobenzaldehyde) and ultraviolet fluorescence with Wood's lamp. - **Congenital hypothyroidism:** Screened by thyroid-stimulating hormone (TSH) measurement. - **Congenital adrenal hyperplasia:** Detected by hyponatremia, hyperkalemia, elevated 17-hydroxyprogesterone, and increased plasma renin activity. - **Inherited hyperbilirubinaemias:** Diagnosed by total and conjugated bilirubin levels.
The authors emphasize that newborn screening programs should include congenital hypothyroidism, phenylketonuria, cystic fibrosis, and others like maple syrup urine disease and galactosaemia, using basic lab facilities.
**Clinical Implications:** Early diagnosis of IEMs using simple, inexpensive tests can prevent severe outcomes like mental retardation, coma, and death. The authors advocate for a structured approach involving a team of pediatricians, clinical chemists, and dieticians. They stress that lack of advanced equipment should not deter screening and diagnosis in developing countries. Collaboration with international organizations like the International Federation of Clinical Chemistry is recommended to improve diagnostic capacity.