Inherited Metabolic Disorders

Inherited Metabolic Disorders refer to medical conditions which are caused by genetic defects mostly inherited from both parents that interfere with the body's metabolism. Metabolism is the complex set of chemical reactions that our body uses to maintain life, including energy production. Special enzymes break down food or certain chemicals so our body can use them right away for fuel or store them. Also, certain chemical processes break down substances that our body no longer needs, or make those it lacks.

IMD are a complex group of disorders, due to an inborn deficiency of a particular enzyme, functions of one or more organs are affected. The onset and severity depends on the degree of deficiency of the particular enzyme and the organ of affection. Most diseases manifest in the childhood.

In Children, few early symptoms include: Apnea, Lethargy, Poor Feeding, Tachypnoea, Vomiting. There are enormous numbers of diseases with wide range of systems affected — nearly every organ can be affected:

• Growth failure, failure to thrive, weight loss
• Developmental delay, seizures, dementia, encephalopathy, stroke
• Deafness, blindness, pain agnosia
• Skin rash, abnormal pigmentation, lack of pigmentation, excessive hair growth
• Dental abnormalities
• Immunodeficiency, thrombocytopenia, anemia, enlarged spleen, enlarged lymph nodes
• Many forms of cancer
• Recurrent vomiting, diarrhea, abdominal pain
• Excessive urination, renal failure, dehydration, edema
• Hypotension, heart failure, enlarged heart, hypertension, myocardial infarction
• Hepatomegaly, jaundice, liver failure
• Unusual facial features, congenital malformations
• Abnormal behavior, depression, psychosis
• Joint pain, muscle weakness, cramps
• Hypothyroidism, adrenal insufficiency, hypogonadism, diabetes mellitus

They need a high index of suspicion to be diagnosed by an experienced child specialist. The confirmation is through biochemical tests and genetic tests.

Common Screening Tests

• Ferric chloride test (turned colors in reaction to various abnormal metabolites in urine)
• Ninhydrin paper chromatography (detected abnormal amino acid patterns)
• Guthrie bacterial inhibition assay (detected a few amino acids in excessive amounts in blood)

Modern Diagnostic Tools

• Quantitative measurement of amino acids in plasma and urine
• Urine organic acid analysis by Gas chromatography-mass spectrometry
• Plasma acylcarnitines analysis by mass spectrometry
• Urine purines and pyrimidines analysis by Gas chromatography-mass spectrometry

Specific Diagnostic Tests

• Tissue biopsy or necropsy: liver, muscle, brain, bone marrow
• Skin biopsy and fibroblast cultivation for specific enzyme testing
• Specific DNA testing

How is BMT curative? Certain cells produced in the bone marrow produce the particular enzymes deficient in a particular IMD. When healthy donor cells are transplanted, they populate the body and the brain and start producing the necessary enzyme. This leads to a gradual improvement in the organ functions and stabilizes the brain.

Diseases Curable with BMT

• Hurlers Syndrome
• Morteaux-Lamy Syndrome
• Childhood onset cerebral X-linked Leukodystrophy
• Globoid Cell Leukodystrophy
• Metachromatic leukodystrophy
• α-Mannosidosis
• Osteopetrosis etc.

Who is the best donor? As there are rarely matched unaffected siblings, alternate donors are the best options. In certain conditions like Hurler's syndrome, Cord Blood Transplants have given excellent results. However, HAPLOIDENTICAL TRANSPLANTS are now providing nearly 100% chance of finding a donor.